Document nNrV5yZqQYKrG5dBvogxOY4v6
Environmental risk evaluation report: Trideca-1,1,1,2,2,3,3,4,4,5,5,6,6fluorohexane (CAS no. 355-37-3)
Chief Scientist's Group report
Month 2021
Version: XXXXXX/R (project code number / if required)
Commented [MCC1]: To be added. Page numbers to be updated after final review.
We are the Environment Agency. We protect and improve the environment.
We help people and wildlife adapt to climate change and reduce its impacts, including flooding, drought, sea level rise and coastal erosion.
We improve the quality of our water, land and air by tackling pollution. We work with businesses to help them comply with environmental regulations. A healthy and diverse environment enhances people's lives and contributes to economic growth.
We can't do this alone. We work as part of the Defra group (Department for Environment, Food & Rural Affairs), with the rest of government, local councils, businesses, civil society groups and local communities to create a better place for people and wildlife.
Published by:
Environment Agency Horizon House, Deanery Road, Bristol BS1 5AH
Author(s): Chemicals Assessment Unit
Keywords: Polyfluorinated alkyl substances; PFAS; 1H-Perfluorohexane;
www.gov.uk/environment-agency
Environment Agency 2021
All rights reserved. This document may be reproduced with prior permission of the Environment Agency.
Further copies of this report are available from our publications catalogue: www.gov.uk/government/publications or our National Customer Contact Centre: 03708 506 506
Environment Agency's Project Manager: Simon Hoy
Citation: Environment Agency (2021) Environmental risk evaluation report: Trideca1,1,1,2,2,3,3,4,4,5,5,6,6-fluorohexane (CAS no. 355-37-3). Environment Agency, Bristol.
Email: research@environmentagency.gov.uk
2 of 86
Contents
Research at the Environment Agency..................................................................................6 Acknowledgements..............................................................................................................7 Executive summary .............................................................................................................8 Introduction ........................................................................................................................10 1 Substance identity .......................................................................................................12
1.1 Name and other identifiers....................................................................................12 1.2 Structurally related substances.............................................................................12 1.3 Transformation products .......................................................................................13 2 Analytical chemistry.....................................................................................................14 2.1 Regulatory and academic methods ......................................................................14 3 Import, manufacture and uses.....................................................................................16 4 Summary of relevant regulatory activities....................................................................18 4.1 Europe ..................................................................................................................18 4.2 Regulatory activity outside Europe .......................................................................19 4.3 Other international agreements ............................................................................20 5 Physico-chemical properties .......................................................................................21 5.1 Vapour pressure ...................................................................................................22 5.2 Surface tension.....................................................................................................24 5.3 Water solubility .....................................................................................................25 5.4 Partition co-efficient (n-octanol/water; log KOW) ....................................................28 5.5 n-Octanol/air partition coefficient (log KOA) ...........................................................30 5.6 Dissociation constant............................................................................................32 6 Environmental fate properties .....................................................................................33 6.1 Degradation ..........................................................................................................33 6.2 Environmental distribution ....................................................................................37
3 of 86
6.3 Long range transport potential ..............................................................................40 6.4 Bioaccumulation ...................................................................................................42 7 Ecotoxicology ..............................................................................................................45 7.1 Aquatic compartment............................................................................................45 7.2 Terrestrial compartment........................................................................................49 7.3 Microbiological activity in sewage treatment systems ...........................................49 7.4 Atmospheric effects ..............................................................................................50 8 Mammalian toxicology.................................................................................................52 8.1 Toxicokinetics .......................................................................................................52 8.2 Repeated dose toxicity .........................................................................................52 8.3 Mutagenicity..........................................................................................................53 8.4 Carcinogenicity .....................................................................................................54 8.5 Toxicity to reproduction (effects on fertility and developmental toxicity) ...............55 8.6 Summary of mammalian toxicology ......................................................................55 9 Environmental hazard assessment .............................................................................56 9.1 Classification and labelling ...................................................................................56 9.2 Assessment of endocrine disrupting (ED) properties............................................57 9.3 PBT and vPvB assessment ..................................................................................57 9.4 Groundwater hazard .............................................................................................58 9.5 Greenhouse gas hazard .......................................................................................59 9.6 Limit values...........................................................................................................60 10 Exposure assessment..............................................................................................62 10.1 Environment ......................................................................................................62 11 Risk characterisation................................................................................................67 12 Conclusions and recommendations .........................................................................69 12.1 Conclusion.........................................................................................................69
4 of 86
12.2 Recommendations.............................................................................................69 13 References...............................................................................................................71 14 List of abbreviations .................................................................................................76 Appendix A: Literature search............................................................................................81 Appendix B: QSAR models................................................................................................82 Would you like to find out more about us or your environment? ........................................85
5 of 86
Research at the Environment Agency
Scientific research and analysis underpins everything the Environment Agency does. It helps us to understand and manage the environment effectively. Our own experts work with leading scientific organisations, universities and other parts of the Defra group to bring the best knowledge to bear on the environmental problems that we face now and in the future. Our scientific work is published as summaries and reports, freely available to all.
This report is the result of research commissioned by the Environment Agency's Chief Scientist's Group.
You can find out more about our current science programmes at httos://www.clov.uk/government/orqanisations/environment-aqencv/about/research
If you have any comments or questions about this report or the Environment Agency's
other scientific work, please contact
@environment-agency.gov.uk.
Professor Doug Wilson Chief Scientist
6 of 86
Acknowledgements
The co-operation and additional information provided by the sole UK importer, AGC Chemicals Europe, Ltd., is acknowledged.
7 of 86
Executive summary
There is growing regulatory concern at international level about the emissions of per- and polyfluoroalkyl substances (PFAS) to the environment. This is due to their extreme persistence, which leads to long-term exposure of both people and wildlife. High levels of exposure to certain PFAS has also been shown to cause harmful effects in humans and some have been declared to be `Persistent Organic Pollutants' (POPs) under the United Nations Environment Programme (UNEP) Stockholm Convention.
The UK Government is developing an action plan to address the concerns arising from PFAS. As a contribution to this work, the Environment Agency is reviewing PFAS that are known to be used at two UK production facilities. The substance reviewed in this evaluation report is trideca-1,1,1,2,2,3,3,4,4,5,5,6,6-fluorohexane, also known as 1H-perfluorohexane (CAS number 355-37-3).
1H-Perfluorohexane is a PFAS that belongs to the group of hydrofluorocarbons. It is imported to the UK and used as an industrial non-reactive processing aid at a single site.
The Environment Agency has identified publicly available information on the regulatory status, uses, physico-chemical properties, environmental fate and (eco)toxicity of 1H-perfluorohexane and has reviewed this information for reliability. Further information has also been sought from the UK importer. The data have then been used to conduct an environmental hazard and risk assessment. Human health hazards have only be reviewed in so far as they are relevant for the environmental assessment. Potential risks to people following environmental exposure have not been addressed.
1H-Perfluorohexane is not readily biodegradable, does not hydrolyse and has a long atmospheric half-life. In addition, there is no information on degradation rates or half-lives available from simulation studies. 1H-Perfluorohexane is therefore considered to be potentially persistent or very persistent (P/vP). An experimental fish bioconcentration study and predictions using quantitative structure-activity relationships indicate that 1H-perfluorohexane is not bioaccumulative (B) in aquatic organisms. Bioaccumulation in airbreathing organisms is unlikely to be high, but there is some uncertainty in this conclusion. 1H-Perfluorohexane does not meet the criteria to be considered toxic (T). 1HPerfluorohexane is therefore not considered to be PBT or vPvB.
Draft criteria have been proposed to identify chemicals that are persistent, mobile and toxic (PMT) or very persistent and very mobile (vPvM). 1H-Perfluorohexane does not meet the draft PMT/vPvM criteria.
An exposure assessment based on information provided by the UK importer has not identified risks for fresh and marine surface waters. However, 1H-perfluorohexane has an atmospheric half-life of 31 years and it could make a contribution to global warming based on analogy with other hydrofluorocarbons.
A number of recommendations are made to the UK importer of 1H-perfluorohexane to improve the data package to allow a more robust assessment of the environmental hazards
8 of 86
Commented [MS2]: Very persistent is a regulatory recognised phrase, not extreme persistence.
and risks posed by 1H-perfluorohexane. This report, along with others in this series, will be used by the Environment Agency to inform the UK Government action plan on PFAS and the PFAS Regulatory Management Options Analysis (RMOA) being conducted under the UK REACH Regulation.
9 of 86
Introduction
There is growing international concern about the emissions of per- and polyfluoroalkyl substances (PFAS) to the environment. This is principally due to their extreme persistence, which could lead to long-term irreversible exposure of both people and wildlife. High levels of exposure to certain PFAS has also been shown to cause harmful effects in humans and some have been declared to be `Persistent Organic Pollutants' (POPs) under the United Nations Environment Programme (UNEP) Stockholm Convention.
The UK Government is developing an action plan to address the concerns arising from PFAS. As a contribution to this work, the Environment Agency is reviewing substances that are being used at two known production facilities in the UK, namely AGC Chemicals Europe, Ltd. of Thornton Cleveleys, Lancashire and F2 Chemicals Ltd of Preston, Lancashire. Based on information provided by these companies, a provisional list of PFAS for further consideration was drawn up. This was narrowed down to the following twelve substances which were, at the time, registered at more than 1 tonne per annum under the EU REACH Regulation (European Commission, 2020). Additionally a potential unregistered substitute for perfluoroctanesulfonic acid (PFOS, which is a known POP) was included that had been identified from UK surface water monitoring. All of the substances chosen for further evaluation are listed below, initially using their EU-registered name:
Ammonium difluoro[1,1,2,2-tetrafluoro-2-(pentafluoroethoxy)ethoxy]acetate - also known as perfluoro(2-ethoxy-2-fluoroethoxy)acetic acid ammonium salt or EEA-NH4 (CAS no. 908020-52-0)
Trideca-1,1,1,2,2,3,3,4,4,5,5,6,6-fluorohexane - also known as 1H-perfluorohexane or 1H-PFHx (CAS no. 355-37-3)
3,3,4,4,5,5,6,6,6-Nonafluorohexene - also known as perfluorobutylethylene or PFBE (CAS no. 19430-93-4)
1,1,1,2,2,3,3-Heptafluoro-3-[(trifluorovinyl)oxy]propane - also known as perfluoro(propyl vinyl ether) or PPVE (CAS no. 1623-05-8)
(E)-1,1,1,2,3,4,5,5,5-nonafluoro-4-(trifluoromethyl)pent-2-ene - also known as perfluoro(4-methyl-2-pentene) or PFMP (CAS no. 3709-71-5)
1,1,1,2,2,3,3,4,5,5,5-Undecafluoro-4-(trifluoromethyl)pentane - also known as perfluoroisohexane or PFiHx (CAS no. 355-04-4)
1,1,2,2,3,3,4,5,5,6-Decafluoro-4,6-bis(trifluoromethyl)cyclohexane - also known as perfluoro-1,3-dimethylcyclohexane or PFDMC (CAS no. 335-27-3)
Perfluorooctane or PFO (CAS no. 307-34-6)
Perflunafene - also known as perfluorodecalin or PFD (CAS no. 306-94-5)
Perfluoroperhydrophenanthrene - also known as perfluorophenanthrene or PFPh (CAS no. 306-91-2)
Hexafluoropropene or HFP (CAS no. 116-15-4)
10 of 86
Commented [MS3]: See previous comment, very persistent.
Octafluoropropane - also known as perfluoropropane or PFP (CAS no. 76-19-7) The additional unregistered substance also being considered is: 6:2 Chlorinated polyfluorinated ether sulfonate - also known as `F-53B' (CAS no. 73606-
19-6) This report summarises the evaluation of the substance highlighted above in bold (i.e. 1H-perfluorohexane), to address the following questions: 1. What data are currently available, and are they sufficiently reliable to assess its
environmental hazards and risks? 2. Can we establish numerical exposure limits for assessing environmental impacts
(e.g. for use under permitting regimes)? 3. Is it potentially able to reach remote environments and what is its groundwater
contamination potential? 4. Is it a potential candidate for future risk management? 5. What information gaps remain, and what is the most appropriate way of obtaining
this information? Information on the substance's properties and uses is provided on the European Chemicals Agency (ECHA) public dissemination website. Unless stated otherwise, the website and data provided by the Registrant are the source of the information for this report. This report describes the substance and its structural analogues, its analytical chemistry, manufacture and use, regulatory status and then various environmentally relevant properties. This is followed by an environmental hazard assessment in Section 9, and an exposure and risk assessment in Sections Error! Reference source not found. and Error! Reference source not found.. The final section (Section Error! Reference source not found.) summarises our findings. Although the focus of this evaluation is on environmental hazards and risks, there is a summary of mammalian toxicology information, where available and relevant. However, this report is not intended to provide a full consideration of hazards, exposure and risks to human health. This is not a formal UK REACH Evaluation.
11 of 86
1 Substance identity
1.1 Name and other identifiers
Table 1.1 Substance identifiers Public name IUPAC name CAS name EC number CAS number Index number in Annex VI of the CLP Regulation Molecular formula Molecular weight SMILES code Synonyms
Type of substance
Trideca-1,1,1,2,2,3,3,4,4,5,5,6,6-fluorohexane 1,1,1,2,2,3,3,4,4,5,5,6,6-Tridecafluorohexane 1H-Perfluorohexane 206-581-9 355-37-3 Not applicable
C6HF13 320.05 C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F 1H-Perfluorohexane ; 1H-Tridecafluorohexane ; 1,1,1,2,2,3,3,4,4,5,5,6,6-Tridecafluorohexane ; Hexane, tridecafluoro- ; Trideca1,1,1,2,2,3,3,4,4,5,5,6,6-fluorohexane ; Hexane, 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro- ; tridecafluorohexane; AsahiklinTM AC-2000) Mono-constituent
Figure 1.1 Structural formula of 1H-perfluorohexane representing the atoms and how they are bonded to each other
The substance is called 1H-perfluorohexane throughout this report.
1.2 Structurally related substances
1H-Perfluorohexane is a hydrofluorocarbon (HFC), containing carbon, fluorine and one hydrogen atom. It is highly fluorinated and lacks functional groups such as acids, ethers or alcohols that characterize other PFAS categories (OECD, 2018).
12 of 86
The carbon-fluorine bond is very strong (up to 546 kJ/mol in tetrafluoromethane) and so highly fluorinated substances are much less reactive than their hydrocarbon analogues.
Potential structural analogues of 1H-perfluorohexane include perfluoroalkanes (perfluorocarbons or PFCs) such as perfluorohexane (CAS no. 355-42-0), which is summarised in Table 1.2, and perfluoroisohexane (CAS no. 355-04-4). Since this latter substance is branched, the Environment Agency has not selected it for inclusion (although an evaluation has been performed for this series of reports). Due to the limited data available for these substances, they have not been considered in detail for this report.
Table 1.2 Name
Substance identifiers for selected analogues of 1H-perfluorohexane Tetradecafluorohexane
CAS number
355-42-0
EC number
206-585-0
Structural formula
F
F
F
F
F
F
F
F
Molecular formula Molecular weight SMILES code Synonyms Comment
F
F
F
F
F
F
C6F14
338 g/mol
C(C(C(C(F)(F)F)(F)F)(F)F)(C(C(F)(F)F)(F)F)(F)F
Perfluorohexane
This substance has a fluorine atom in place of the hydrogen atom that is present in 1H-perfluorohexane, giving it a slightly higher molecular weight.
1.3 Transformation products
Although the carbon-fluorine bond is very strong, a slow reaction occurred in both the photolysis and ready biodegradation tests (see Section 6). The transformation products were not identified but are likely to include perfluorohexan-1-ol, which might in turn slowly oxidise further to perfluorohexanoic acid. The properties of these substances have not been considered for the purposes of this evaluation, although they are likely to be persistent.
13 of 86
Commented [MS4]: Is this correct, does not look right to me but I don't use these often. Two `C's in the middle?
Commented [MS5]: Not proven. This has not been looked at in AGC's studies but there is some degradation. Could even be loss of test material. Note, AGCCE have tried to measure PFHxA levels in ETFE (done by AGC Japan). No PFHxA was detected subject to a LOD of 7 ppb (from AGC's contributions to the PFHxA consultation, July 2020 and September 2021 SEAC consultation).
2 Analytical chemistry
2.1 Regulatory and academic methods
According to Corrigendum 1 of REACH (EC, 2007) and Article 119 (Electronic Public Access) the Registrant has to be able to provide "analytical methods if requested in accordance with Annexes IX or X which make it possible to detect a dangerous substance when discharged into the environment as well as to determine the direct exposure of humans". 1H-Perfluorohexane is not classified as hazardous, and the EU Registrant has not provided such analytical details in their registration dossier (ECHA, 2020a). However, a validated analytical method was supplied to the Environment Agency by the UK importer. The method was developed as part of a GLP study (Unpublished, 2017a), and validated in accordance with EU guidance (EC, 2000). It uses gas chromatography with mass spectrometric detection (GC-MS) for the quantitative analysis of the substance in aqueous solution.
Method development included (though was not limited to) solvent selection, suitability of detector and chromatographic separation column. Optimisation was performed throughout the development to improve retention time stability, assess carry-over and improve peak shape. Only the conditions of the final method are reported in Unpublished (2017a). Full details are not presented in this evaluation as they are not in the public domain. Validation was performed for specificity, calibration curve (R2 0.995, in the range 0.008 to 6.0 mg/L), accuracy (99 and 114 or 81% at 0.01 and 5 mg/L, respectively) and repeatability (2.4 and 4.8 or 5.3% at 0.01 and 5 mg/L, respectively), limit of quantification (LOQ) (0.01 mg/L), analytical system stability, stock solution stability and storage stability of samples. The Environment Agency assessed the method as valid as it meets is requirements set out in EC (2000).
In addition, the Environment Agency searched the academic literature for analytical methods for the detection of 1H-perfluorohexane in environmental matrices (water, fresh and marine; soil, sediment, sludge and air). Thousands of hits for methods relating to short chain perfluorocarbons were obtained, although no specific methods for 1H-perfluorohexane were identified.
Analytical monitoring of 1H-perfluorohexane in environmental matrices is not documented as part of national or international monitoring programmes. It is, however, present in databases operated by the Swedish Chemicals Agency, OECD Global Database, EPA ToxCast/Tox21 and several others. No validated associated analytical methods were presented alongside. The US EPA states that methods for measurement of volatile PFAS in air are under development and undergoing validation (US EPA 2021).
The website of the contract laboratory Eurofins Test America (www.EurofinsUS.com/PFAS) indicates they have a validated method for the quantification of volatile perfluoroalkyl carboxylic acids in air. This method may be adaptable to allow measurement of 1H-perfluorohexane.
14 of 86
The Environment Agency considers that a robust analytical method will include the following details: Instruments and consumables including chromatographic column, temperature, mobile
phase composition, flow rates, gradient or isocratic separation and the detector optimisation and configuration. Certified reference standards, calibration range and sensitivity, limit of detection, limit of quantification, column recoveries, stability and reproducibility. Sample preparation including clean-up consumables, concentration techniques and use of internal standards (plus justification for choice) for validation and recoveries, etc. Identification and discussion of technical limitations.
15 of 86
3 Import, manufacture and uses
Although the UK left the European Union (EU) at the end of January 2020, European legislation in place by December 2020 has been retained in UK law, and ECHA is still the most relevant source of information about chemicals on the UK market at the time of writing.
1H-Perfluorohexane is registered under the EU REACH Regulation at a supply level of 10 to 100 tonnes/year. There is one EU REACH Registrant, AGC Chemicals Europe, Ltd. (www.agcce.com) (located in the Netherlands). The substance is imported into the UK for use at AGC Chemicals Europe, Ltd.'s manufacturing site at Thornton Cleveleys near Blackpool, Lancashire.
According to the ECHA website, 1H-perfluorohexane is used at industrial sites as a nonreactive processing aid (no inclusion into or onto articles).
AGC Chemicals Europe, Ltd. has an environmental permit (ref: EPR/BU5453IY) under the Environmental Permitting (England and Wales) Regulations 2016. It produces two main product streams:
polytetrafluoroethylene (PTFE) with a capacity up to 4 000 tonnes/year
ethylene-tetrafluoroethylene (ETFE) with a capacity up to 2 000 tonnes/year
An overview of uses provided in the EU REACH registration information on the ECHA website is presented in Table 3.1.
Table 3.1 Overview of uses Life cycle stage Use(s)
ERC2: Formulation into mixture
Formulation
PROC 1: Chemical production or refinery in closed process without likelihood of exposure or processes with equivalent containment conditions
PROC 2: Chemical production or refinery in closed continuous process with occasional controlled exposure or processes with equivalent containment conditions
PROC 3: Manufacture or formulation in the chemical industry in closed batch processes with occasional controlled exposure or processes with equivalent containment conditions
PROC 4: Chemical production where opportunity for exposure arises
PROC 8a: Transfer of substance or mixture (charging and discharging) at nondedicated facilities
PROC 8b: Transfer of substance or mixture (charging and discharging) at dedicated facilities
PROC 9: Transfer of substance or mixture into small containers (dedicated filling line, including weighing)
16 of 86
Commented [MS6]: 1H-perfluorohexane is not related to the manufacture of PTFE.
Life cycle stage Use(s)
PROC 15: Use as laboratory reagent PROC28: Manual maintenance (cleaning and repair) of machinery
Use as a non-reactive processing aid ERC4: Use of non-reactive processing aid at industrial site (no inclusion into or onto article)
Uses at industrial sites
PROC 1: Chemical production or refinery in closed process without likelihood of exposure or processes with equivalent containment conditions PROC 2: Chemical production or refinery in closed continuous process with occasional controlled exposure or processes with equivalent containment conditions PROC 3: Manufacture or formulation in the chemical industry in closed batch processes with occasional controlled exposure or processes with equivalent containment conditions PROC 4: Chemical production where opportunity for exposure arises PROC 8a: Transfer of substance or mixture (charging and discharging) at nondedicated facilities PROC 8b: Transfer of substance or mixture (charging and discharging) at dedicated facilities PROC 9: Transfer of substance or mixture into small containers (dedicated filling line, including weighing) PROC 15: Use as laboratory reagent
Recovery of a non-reactive processing aid ERC4: Use of non-reactive processing aid at industrial site (no inclusion into or onto article)
Uses by professional workers
PROC 4: Chemical production where opportunity for exposure arises PROC 8a: Transfer of substance or mixture (charging and discharging) at nondedicated facilities
None identified in registration dossier
Consumer Uses None identified in registration dossier
Article service life
None identified in registration dossier
Commented [MS7]: AGCCE is considering whether ERC5 is more appropriate now we have new information of residual 1Hperfluorohexane in ETFE. This will be consider at next EUREACH and UK-REACH updates.
17 of 86
4 Summary of relevant regulatory activities
4.1 Europe
4.1.1 European Chemicals Agency (ECHA)
The Public Activities Co-ordination Tool (PACT) (https://echa.europa.eu/pact accessed July 2020) provides an overview of the substance-specific activities that EU regulatory authorities are working on under the EU REACH and CLP Regulations. No substance-specific activities have been identified for 1H-perfluorohexane on PACT.
Between May and July 2020, the national authorities of Germany, the Netherlands, Norway, Sweden and Denmark invited interested parties to send in evidence and information on the use of PFAS in preparation for a joint EU REACH restriction proposal. The current scope of the work is wide and includes all substances that contain at least one aliphatic -CF2- or CF3 element (ECHA, 2021). 1H-Perfluorohexane is therefore within scope of this initiative.
4.1.2 European Food Safety Agency (EFSA)
EFSA provides scientific advice on safety of food additives, enzymes, flavourings, processing aids and other substances intentionally added to food; safety of food packing and other food contact materials.
A search of the EFSA website (http://www.efsa.europa.eu/) did not identify 1H-perfluorohexane as being evaluated or noted in any published scientific opinions.
4.1.3 Oslo and Paris Convention for the Protection of the Marine Environment of the North-East Atlantic (OSPAR)
The Oslo and Paris Convention for the Protection of the Marine Environment of the NorthEast Atlantic (OSPAR) is a mechanism by which 15 national governments and the EU cooperate to protect marine resources. Much of OSPAR's work on chemicals is now being addressed by REACH activities.
1H-Perfluorohexane is not on the OSPAR List of Substances of Possible Concern (www.ospar.org/work-areas/hasec/chemicals/possible-concern/list, accessed July 2020). 1H-Perfluorohexane is also not on the list of Chemicals for Priority Action adopted in 2002 (www.ospar.org/work-areas/hasec/chemicals/priority-action, accessed July 2020).
Commented [MS8]: `All PFAS' RoI published July 2021. AGC have provided significant input to the two calls for evidence and questionnaires relating to this proposal.
Commented [MS9]: 1H-perfluorohexane is being considered under the PFHxA restriction proposal with SEAC recommendation now with EU COM. This applies in the EU but not UK. 1H-perfluorohexane is considered a PFHxA related substance. If restricted under the PFHxA restriction, it should be excluded from the `all PFAS' restriction (so as not to be double regulated).
AGC has contributed to the RAC, SEAC and consultation process for the PFHxA restriction proposal.
18 of 86
4.2 Regulatory activity outside Europe
4.2.1 United States
1H-Perfluorohexane is not listed as one of the substances undergoing risk evaluation as part of US EPA's existing chemical initiative under the Toxic Substances Control Act (TSCA) to determine whether they present an unreasonable risk to public health or the environment under the conditions of use (US EPA, 2020).
4.2.2 Canada
A search did not identify 1H-perfluorohexane as being under assessment under the
Prohibition
of
Certain
Toxic
Substances
Regulations,
2012
(https://www.canada.ca/en/environment-climate-change/services/canadian-environmental-
protection-act-registry/substances-list/toxic.html, accessed July 2020).
4.2.3 Australia
A search did not identify 1H-perfluorohexane as being under assessment under the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (https://www.nicnas.gov.au/chemical-information/imap-assessments/imap-assessments, accessed July 2020).
4.2.4 New Zealand
A search did not identify 1H-perfluorohexane as being under assessment under the Hazardous Substances and New Organisms Act 1996 (https://www.epa.govt.nz/industryareas/hazardous-substances/, accessed July 2020; https://www.epa.govt.nz/industryareas/hazardous-substances/chemical-reassessment-programme/screened-chemicalslist/, accessed July 2020).
4.2.5 Japan
Industrial chemicals are managed under the Chemical Substances Control Law (CSCL),
most
recently
amended
in
2009
(https://www.nite.go.jp/chem/jcheck/list3.action?category=141&request_locale=en,
accessed July 2020). Under the Act there are 3 lists:
Class I Specified Chemicals - 28 substances (persistent, bioaccumulative, toxic) Class II Specified Chemicals - 23 substances (toxic and high risk) Priority Assessment Chemical Substance (PACS), currently 226 substances
1H-Perfluorohexane is not on any of the above lists.
19 of 86
4.3 Other international agreements
4.3.1 United Nations Stockholm Convention on Persistent Organic Pollutants (POPs)
1H-Perfluorohexane is not identified as a POP, and is not currently under evaluation (http://chm.pops.int/TheConvention/ThePOPs/AllPOPs/tabid/2509/Default.aspx, accessed July 2020).
4.3.2 Greenhouse gases
Fluorinated gases (`F-gases') may contribute to climate change due to their global warming potential and they are often used as substitutes for ozone-depleting substances, because they do not damage the atmospheric ozone layer (EC, n.d.). F-gases are regulated under the Ozone-Depleting Substances and Fluorinated Greenhouse Gases (Amendment etc.) (EU Exit) Regulations (2019) which aims to reduce the emission of these gases into the environment. Annex I and II list the F-gases subject to the Regulation and 1Hperfluorohexane is not included.
20 of 86
5 Physico-chemical properties
This evaluation focusses on vapour pressure, water solubility and n-octanol/water partition coefficient, as they are the key physico-chemical end points for the environmental assessment of most organic chemicals. Surface tension and dissociation constant are also considered. The available information is discussed in this section, and a conclusion drawn about which value the Environment Agency considers most suitable for the further evaluation of this substance.
The source of this information is the publicly available EU REACH registration database (ECHA, 2020a; accessed July 2021) unless otherwise indicated. The reliability scores provided in the full registration for individual studies are cited. These scores have presumably been generated in accordance with the ECHA R.4. Guidance Document (ECHA, 2011).
The Environment Agency has evaluated original study reports where provided. Where an independent evaluation has not been possible for a study, or the EU REACH registration dossiers lack sufficient supporting information, this is noted in the text (except in the case of data presented in academic journals or obtained using quantitative structure-activity relationship (QSAR) models).
Where an endpoint value is missing from the EU REACH registration dossier, or an initial review raised questions around the validity of an experimentally derived value, the assessment has been supplemented with information from analogues (see Section 1) and openly available in silico QSAR models. REACH registration data for the analogues are taken at face value, although preference is given to regulatory reviews (if available). QSAR models are generally considered to be a screening-level tool and measured values are preferable provided that they are sufficiently reliable. Further information is provided in Appendix B.
An overview of physico-chemical data provided by the Registrant or generated by the Environment Agency is presented in Table 5.1.
Table 5.1 Property
Summary of physico-chemical properties for 1H-perfluorohexane
Value(s)
Reliability
Source
Physical state at 20 C and 101.3 kPa
Colourless liquid
Registrant: 1 (key study)
EU REACH Registration dossier
Melting / freezing point
<-80 C at 101.3 kPa (GLP, OECD TG 102; EPA OPPTS830.7200)
Registrant: 1 (key study)
EU REACH Registration dossier
Boiling point
67 C at 101.3 kPa (GLP, OECD TG 103, EPA OPPTS 830.7220)
Registrant: 1 (key study)
EU REACH Registration dossier
Commented [MS10]: The quality of the output of some of these models is poor.
21 of 86
Property Relative density
Vapour pressure
Surface tension
Water solubility
n-Octanol/water partition coefficient (log KOW) n-Octanol/air partition coefficient (log KOA) Dissociation constant
Value(s)
1.68 g/cm3 at 20 C (GLP, OECD TG 109. EPA OPPTS 830.7300)
15 kPa at 20 C (110 mmHg), 19 kPa at 25 C (140 mmHg) (GLP, OECD TG 104, EPA OPPTS 830.7950)
73.2 mN/m at 20C and 90% saturation solubility in water (GLP, OECD TG 115, EU method A.5)
1.5 mg/L at 20 C pH >7.2, <8.25 (GLP, OECD TG 105, EPA OPPTS 830.7840)
4.1 (GLP, OECD TG 117, EPA OPPTS 830.7570)
Reliability Registrant: 1 (key study)
Registrant: 1 (key study)
Registrant: 1 (key study)
Registrant: 1 (key study)
Registrant: 1 (key study)
0.85 (calculated)
-
Not applicable
-
Source EU REACH Registration dossier EU REACH Registration dossier
EU REACH Registration dossier
EU REACH Registration dossier
EU REACH Registration dossier Environment Agency
-
5.1 Vapour pressure
5.1.1 Measured data
The key experimental study in the EU REACH registration dossier was performed according to OECD Test Guideline (TG) 104 (OECD, 2006a) and was compliant with the principles of Good Laboratory Practice (GLP) (Unpublished, 2017a). The Environment Agency has reviewed the full study report.
In brief, the vapour pressure of 1H-perfluorohexane was determined by a static method using a vapour pressure testing manifold. The test item was certified as 100% pure. The method is considered suitable for measurements in the range of 103 and 106 Pa. Analytical grade diethyl ether was used as a reference substance to validate the method. The measured vapour pressure of the diethyl ether at 20 C deviated by < 5% of the literature value and was acceptable. Measurements of the vapour pressure of the test substance were performed in duplicate at 7 temperatures between 20 and 50 C. Based on linear regression, the experimentally derived vapour pressure of 1H-perfluorohexane was 15 kPa at 20 C (110 mmHg) (ECHA, 2020a) and 19 kPa at 25 C (140 mm Hg). The EU REACH Registrant
22 of 86
considers that the data are reliable without restrictions (Klimisch 1), and the Environment Agency agrees that the study was well performed.
5.1.2 Predicted data
No in silico predictive data were presented by the Registrant for this endpoint as there is a valid experimental result.
For comparative purposes, the Environment Agency has considered readily available QSARs to test how they perform for this type of substance. The ChemSpider database and the US EPA CompTox dashboard contain predicted vapour pressures for 1H-perfluorohexane generated from EPISuiteTM, T.E.S.T., ACD/Labs and OPERA software (RSC, 2020a; US EPA, 2020a). Median predicted values are presented in Table 5.2. The Environment Agency converted the values from mmHg to kPa.
Table 5.2 Source
ACD/Labs
Predicted vapour pressures for 1H-perfluorohexane
Prediction method
Predicted vapour pressure (kPa/mmHg) at 25 C
Not available
15.6 kPa
EPISuiteTM Estimation programme MPBPWIN v 1.42
T.E.S.T. (EPISuiteTM v 4.00)
Mean of Antoine and Grain methods
BP = 46.15 C
MP = -98.86 C Not available
117 mmHg 47.2 kPa 354 mmHg
4.20 kPa
OPERA
Not available
31.5 mmHg 651 kPa
4.88 x 103 mmHg
In silico predicted values should always be treated with caution where substances in the training set and external test set are not visible. For the ACD/Labs and MPBPWIN models this information was not available. Therefore no assessment of applicability could be performed. The good agreement between predicted and measured value using the ACD/Labs model may be coincidental.
Structural analogues of 1H-perfluorohexane were included in both the training set and external test sets for the T.E.S.T. and OPERA models. Predicted vapour pressure values are therefore within the applicability domain of both models. Despite this, there is a large difference between the predicted and experimental values, illustrating that the OPERA model in particular is not reliable in this case.
5.1.3 Data from structural analogues
Analogues have not been considered by the Environment Agency as the experimental study data are considered fully reliable.
23 of 86
5.1.4 Additional sources
No relevant references were identified in the literature search.
5.1.5 Recommended value
The Environment Agency considers that a vapour pressure of 15 kPa at 20 C is sufficiently reliable for use in further assessment. This indicates that the substance is moderately volatile.
5.2 Surface tension
5.2.1 Measured data
The key experimental study in the EU REACH registration dossier was carried out according to OECD TG 115 (OECD, 1995), and was GLP compliant (Unpublished, 2017a). The Environment Agency has reviewed the full study report and agrees with the Registrant that the data are reliable without restrictions (Klimisch 1).
The experimentally derived surface tension of 1H-perfluorohexane at 90% of the saturation solubility in water and at 20 C was 73.2 mN/m (ECHA, 2020a and Unpublished, 2017a). The results indicate that 1H-perfluorohexane is not surface active (as the surface tension is > 60 mN/m). This is to be expected, as 1H-perfluorohexane does not have any hydrophilic structural groups that can form hydrogen or Van der Waals bonds in water.
5.2.2 Predicted data
For comparative purposes, the Environment Agency has considered readily available QSARs to test how they perform for this type of substance. The ChemSpider database (RSC, 2020a) and US EPA CompTox dashboard (US EPA, 2020a) include predictions of surface tension presented in Table 5.3.
Table 5.3 Predicted Surface tension for 1H-perfluorohexane
Source
T.E.S.T. (EPISuite v 4.00) ACD/Labs Chemspider
Surface tension (mN/m)
8.84 11.6 11.6
These values are clearly different from the reported surface tension of an aqueous solution, and are likely to be for the liquid substance itself. They are not relevant for this evaluation.
5.2.3 Data from structural analogues
Chernyshev and Skliar (2014) reported a small decrease in the surface tension of deionised water in the presence of perfluorocarbon vapours in an experiment using perfluoropentane
24 of 86
and perfluorohexane at 20 C. The surface tension of the water reduced from 72 mN/M to 64.6 mN/M in the presence of perfluoropentane and 66.7 mN/M in the presence of perfluorohexane. It was suggested that a separate perfluorocarbon layer may form at the water-air interface in aqueous solution.
5.2.4 Recommended value
Surface tension in water is important because it can affect the measurement and interpretation of other physico-chemical properties such as water solubility and n-octanol/water partition coefficients. The Environment Agency considers that 1H-perfluorohexane will not be surface active in aqueous solution.
5.3 Water solubility
5.3.1 Measured data
The key experimental study for water solubility in the EU REACH registration dossier was carried out according to OECD TG 105 (OECD, 1995a) (slow-stirring flask method) and was GLP compliant (Unpublished, 2017a). The Environment Agency has reviewed the full study report.
The main study used containers filled with 116 mL (by weight) of double distilled water, sealed with a septum lidded cap to prevent evaporation of the test substance (one of which was used as a blank control). Aliquots of 10 L of 1H-perfluorohexane were injected through the septum of three containers using a syringe to provide a nominal concentration of 145 mg/L. The vessels were placed on a magnetic stirring device and gently stirred at 100 revolutions per minute for 24, 48 or 72 hours. Blank vessels were stirred for 72 hours. Turbulent mixing of the two phases was actively avoided and the head space of the containers was minimised. The temperature was maintained at 19.7 0.3 C.
After the stirring period, three samples of 2 mL were aliquoted from each container to a 10 mL vial containing 40 L of dimethylsulfoxide (DMSO) and analysed. With the exception of the blank test vessels the pH of the solution in each dosed container was also measured. Analysis was performed using the validated GLP method presented in Section Error! Reference source not found.. Seven concentrations (analysed in duplicate) were used to construct the calibration curve. Responses were excluded from the curves if the back calculated accuracy was > 15% from the nominal concentration. The coefficient of correlation was > 0.99 for each curve.
The results from the main study met the validity criteria of OECD TG 105 (OECD, 1995a) and EC (2000), i.e. the maximum difference in the measured concentration between the 24, 48 and 72 hour stirred samples was below 15%, and the stability of the analytical system met the criterion that the coefficient of variation should be below 20%. No test substance was detected in samples from the control containers.
25 of 86
The reported water solubility after 72 hours was 1.5 mg/L at 19.7 0.3 C (pH 7.2 to 8.5). The authors of the study report consider that it is highly unlikely that a more accurate value could be measured due to the high volatility of 1H-perfluorohexane.
The EU REACH Registrant assessed the data to be reliable without restrictions (Klimisch 1) (ECHA, 2020a).
5.3.2 Predicted data
No in silico predictive data were presented by the EU REACH Registrant for this endpoint as there is a valid experimental result.
For comparative purposes, the Environment Agency has considered readily available QSAR software to test how they perform for this type of substance. The ChemSpider database and US EPA CompTox dashboard contained predicted water solubility endpoint values generated from EPISuiteTM, T.E.S.T. and OPERA software (RSC, 2020a; US EPA, 2020a). These values are presented in Table 5.4. Values were converted by the Environment Agency from mol/L to mg/L using a molecular weight of 338.04 g/mol.
Table 5.4 Predicted water solubility values for 1H-perfluorohexane
Model EPISuiteTM water solubility estimate from log KOW (WSKOW v1.41) EPISuiteTM water solubility estimate from fragments (WATERNT v1.01 est.) T.E.S.T. (EPISuiteTM v 4.00)
ACD/Labs
OPERA
Details Log KOW used: 5.41 (estimated)
Water solubility 0.040 mg/L at 25 C
-
0.0082 mg/L
Predicted value: 7.23 x 10-6 mol/L
Low confidence, no structural analogues in training sets. 7.00 mol/L
Low confidence, no structural analogues in training sets. Predicted value: 3.04 x 10-5 mol/L
Global applicability domain: outside
Local Applicability domain index: 0.341
Confidence Interval 0.498
2.3 mg/L 2 240 000 mg/L 9.7 mg/L
In silico predicted values should always be treated with caution where substances in the training set and external test set are not visible.
Guidance provided with the WSKOWWIN model indicates that the relationship between the experimental and predicted values for a training set of 1 450 compounds was good, with an R2 of 0.97, standard deviation of 0.409 and an average deviation of 0.313. The validation set contained several perfluorocarbons (PFCs) (see
26 of 86
Appendix B) and it is likely that the predicted value for 1H-perfluorohexane falls within the applicability domain of the model.
Guidance provided with the WATERNT model indicates that the relationship between the experimental and predicted values for a training set of 4 636 compounds was good, with an R2 of 0.85, standard deviation of 1.045 and an average deviation of 0.796. The validation set contained several perfluorocarbons (PFCs) (see Appendix B) and it is likely that the predicted value for 1H-perfluorohexane falls within the applicability domain of the model.
The Environment Agency considers the value predicted using ACD/Labs to be an error as such a high value is inconsistent with the observation of clear phase separation in the water solubility study. It will not be considered further.
No close structural analogues of 1H-perfluorohexane were included in either the training set or external test sets of the T.E.S.T. model. Therefore, predicted values from T.E.S.T. are considered to be outside the applicability domain of the model.
For the OPERA model, structural analogues of 1H-perfluorohexane were included in the external test set (including perfluoropropane), but not the training set. Perfluoropropane is considered to be outside the global applicability domain but has a high local applicability domain index (> 0.6). The predicted value of 9.7 mg/L for 1H-perfluorohexane therefore has low to moderate confidence.
The in silico predictions therefore suggest that the water solubility of 1H-perfluorohexane may lie in the range 0.008 to 10 mg/L. The model which predicts the closest value to the measured water solubility is T.E.S.T., which may just be coincidence.
5.3.3 Data from structural analogues
Analogues have not been considered in detail as a suitable experimental study is available. However, it is notable that the measured water solubility of perfluorohexane reported in the EU REACH registration of that substance is 0.1 mg/L at 20 C (ECHA, 2020c). The Environment Agency has not evaluated the reliability of this value.
5.3.4 Additional sources
Chernyshev and Skliar (2014) reported that PFCs such as perfluorohexane form colloids in water, which may involve liquid droplets, vapour bubbles or a combination of both phases simultaneously.
5.3.5 Recommended value
A modern experimental study is available for 1H-perfluorohexane, which the EU REACH Registrant considers to be fully reliable. The Environment Agency recognises that the substance is likely to partition significantly from water to air (see Section 6.2.2), and reasonable efforts to minimise losses were made in this instance (in accordance with the
27 of 86
recommendations of OECD, 2019). Whilst pH dependence of water solubility appears unlikely for this substance based on the structure (i.e. there are no obvious acidic or basic functional groups), the study report does not include any discussion of the significant pH variation observed. In addition, the high hydrophobicity of the carbon-fluorine bond may result in colloid formation as observed for similar substances (Chernyshev and Skliar, 2014), and this was not considered in the study. The reported water solubility also appears to be at least an order of magnitude higher than that for the close structural analogue perfluorohexane. Therefore, the Environment suggests that the study may be reliable with restrictions (Klimisch 2).
Predicted values of water solubility ranged from 0.0082 to 9.7 mg/L.
In the absence of a further study to re-visit the pH variability and potential for colloid formation, the Environment considers that the water solubility of 1.5 mg/L at 20 C is a suitable estimate for the purposes of this evaluation.
5.4 Partition co-efficient (n-octanol/water; log KOW)
5.4.1 Measured data
The key experimental study for n-octanol/water dissociation constant in the EU REACH registration dossier was carried out according to OECD TG 117 (OECD, 2004) (high performance liquid chromatography (HPLC) method) and was GLP compliant (Unpublished, 2017a). The Environment Agency has reviewed the full study report.
This method was selected based on a QSAR prediction (see Section 5.4.2), and used a reverse phase ultra-high performance liquid chromatography (UPLC) at 35 C coupled to a refractive index detector, in conjunction with an isocratic mobile phase. 1H-Perfluorohexane does not contain functional groups that will dissociate and therefore the mobile phase was not buffered. Test and reference substances were analysed in duplicate. A single analysis was performed on the blank. It was verified that only one peak was observed in the chromatograms of the 1H-perfluorohexane solutions. The log KOW values of the reference substances ranged from 2.7 to 5.7, and these were used to generate a calibration curve using column capacity factors calculated from the substances' retention times. A log KOW of 4.1 was estimated for 1H-perfluorohexane using this curve. The EU REACH Registrant considers the data to be reliable without restrictions (Klimisch 1), and the Environment Agency agrees that the study was well performed.
In addition, the Chemspider database (RSC, 2020a) reports an experimental log KOW of 6.07, but no further details are available. Therefore the reliability of this value is unknown (Klimisch 4).
5.4.2 Predicted data
Unpublished (2017a) contains a preliminary calculation that was performed using the Rekker method (PrologP 6.0 module in Pallas 3.0, CompuDrug International, USA). This is
28 of 86
Commented [DF11]: There is no requirement in OECD Test Method 105 to study the impact of pH, only to report the pH. The study was run twice, once at pH 7.2/7.3 and once at pH 8.1/8.5. There was no impact on the level of water solubility.
Commented [DF12]: It is unclear what the restrictions are, other than the apparent lack of consideration of pH and colloid formation.
a fragment based method, and is recommended in the OECD test guideline. The log KOW of 1H-perfluorohexane was calculated to be 4.61. However, the study report does not provide any information about whether the training set and external test set contained similar substances, so its reliability cannot be established.
For comparative purposes, the Environment Agency has considered readily available QSAR software to test how they perform for this type of substance. The US EPA CompTox dashboard and ChemSpider database contained estimated log KOW values for 1Hperfluorohexane from ACD/Labs, EPISuiteTM and OPERA (RSC, 2020a; US EPA, 2020a) (Table 5.5).
Table 5.5 Model ACD/Labs
EPISuiteTM OPERA
Predicted log KOW values for 1H-perfluorohexane Details
ACD/LogP ACD/LogD (pH 5.5) ACD/LogD (pH 7.4)
KOWWIN v 1.67 estimate
Predicted value: 3.60 Global applicability domain: Inside Local Applicability domain index: 0.564 Confidence Interval 0.503
log KOW 4.62 4.37 4.37 5.41 3.60
In silico predicted values should always be treated with caution where substances in the training set and external test set are not visible.
This information was not available for the ACD/labs model, so no assessment of the applicability can be performed.
Guidance provided with the KOWWIN model indicates that the relationship between the experimental and predicted values for a validation set of 10 331 compounds was good, with an R2 of 0.94 and standard deviation of 0.47. The training set contained several PFCs (see Appendix B) and it is likely that the predicted value for 1H-perfluorohexane falls within the applicability domain of the model.
For the OPERA model, structural analogues of 1H-perfluorohexane were included in both the training set and external test sets (e.g. perfluoroethane). 1H-Perfluorohexane is considered inside the global applicability domain and has a local applicability domain index of 0.564. The predicted value therefore has moderate confidence.
The in silico predictions therefore suggest that the log KOW of 1H-perfluorohexane may lie in the range 3.6 to 5.41. The model which predicts the closest value to the measured log
29 of 86
KOW is ACD/Labs, but the reliability of this model for this type of substance is unknown and so it may just be coincidence.
5.4.3 Data from structural analogues
Analogues have not been considered in detail as a suitable experimental study is available. A log KOW of 4.5 has been estimated for perfluorohexane based on the ratio of its measured solubility in n-octanol ( 3.0 g/L) and water (0.1 mg/L) (ECHA, 2020c). The Environment Agency has not evaluated the reliability of this value, but it suggests that this type of substance may have a high affinity for organic phases such as lipids.
5.4.4 Additional sources
As noted in Section 5.3.4, PFCs such as perfluorohexane can form colloids in water. It is possible that the same may occur in organic liquids like n-octanol.
5.4.5 Recommended value
A modern experimental study is available for 1H-perfluorohexane, which the EU REACH Registrant considers to be fully reliable. The Environment Agency notes that the method is indirect, in that it uses the retention time on a HPLC column in comparison to a series of reference standards to provide an estimate of KOW. However, highly fluorinated substances may have the potential to form separate phases from water and n-octanol, and this was not investigated as part of the study.
The Environment Agency notes that a high solubility in n-octanol (3.0 g/L) was reported for perfluorohexane. Assuming that this is a reliable measurement of true solubility (which might not be the case, due to colloid formation), and that 1H-perfluorohexane has a similar level of solubility in n-octanol, a log KOW of 3.3 can be estimated for 1H-perfluorohexane using its measured water solubility (1.5 mg/L). Further investigation of n-octanol solubility might be useful to provide an unbounded value.
The experimentally determined log KOW value of 4.1 will be used for the purpose of this evaluation.
5.5 n-Octanol/air partition coefficient (log KOA)
The octanol-air partition coefficient is non-standard endpoint for hazard assessment under REACH. It is used to predict the partitioning behaviour of organic compounds between air and environmental matrices such as soil, vegetation, and aerosol particles (Meylan and Howard, 2005). Methods for measurement and calculation of the value are discussed in Environment Agency (2009).
30 of 86
5.5.1 Measured Data
No experimental log KOA values were presented for 1H-perfluorohexane by the EU REACH Registrant (ECHA, 2020a).
5.5.2 Predicted data
The Environment Agency has estimated a KOA value using the dimensionless Henry's Law constant (log KAW) of 3.25 (see Section 6.2.2) and the recommended log KOW value of 4.1 (Section 5.4) (KOA = KOW/KAW). The resulting log KOA is 0.85. As there is uncertainty in the KAW, the reliability of these derived KOA values is unknown
The US EPA CompTox dashboard and ChemSpider database contained predicted KOA values for 1H-perfluorohexane generated from KOAWIN v1.10 and OPERA software (RSC, 2020a, US EPA, 2020a). These values are presented in Table 5.6.
Table 5.6 Source
Predicted log KOA for 1H-perfluorohexane Details
EPISuiteTM Estimation programme KOAWIN v1.1
Log KOA (log KOW used: 5.41 and KAW used: 4.977 estimated)
ChemSpider (RSC, 2020a)
Log KOA (experimental database): None
OPERA
Global applicability domain: Inside Local Applicability domain index: 0.979 Confidence Interval: 0.803
Calculation
Calculated from log KAW of 3.25 and a log KOW value of 4.1 (KOA = KOW/KAW)
log KOA 0.433
1.57
0.85
In silico predicted values should always be treated with caution where substances in the training set and external test set are not visible.
For the KOAWIN model, the values are estimated from either predicted or experimental KAW and KOW values sourced from HENRYWIN and KOWWIN respectively. The training sets for KOWWIN and HENRYWIN contain several PFCs (see Appendix B) and it is likely the respective predicted value for 1H-perfluorohexane falls within the applicability domains of the two models. Therefore, the predicted KOA for 1H-perfluorohexane can be considered to be predicted with high confidence.
Structural analogues of 1H-perfluorohexane were included in the training and external test sets of the OPERA model. 1H-Perfluorohexane is considered inside the global applicability domain and has a high local applicability domain index (> 0.6), so the prediction has high confidence.
31 of 86
Additionally the US EPA CompTox dashboard also contained log KAW for 1H-perfluorohexane from OPERA (US EPA, 2020a). The reliability of this estimate is unknown.
5.5.3 Data from structural analogues
There are no measured data for structural analogues.
5.5.4 Additional sources
No relevant references were identified in the literature search.
5.5.5 Recommended value
No log KOA values were presented in the EU REACH registration dossier (ECHA, 2020a). In silico predictions for the log KOA of 1H-perfluorohexane were between 0.433 (RSC, 2020a) and 1.57 (US EPA, 2020a). The Environment Agency's estimated value of 0.85 lies within this range, and so is selected for the purposes of this evaluation, although there are uncertainties.
5.6 Dissociation constant
The Environment Agency notes that a dissociation constant is irrelevant for 1H-perfluorohexane as it has no ionisable functional groups. It will remain as a neutral compound at environmentally relevant pH.
32 of 86
6 Environmental fate properties
The same comments about sources of data, reliability scoring and use of supplemental information apply as for Section 5.
6.1 Degradation
6.1.1 Abiotic degradation
Hydrolysis
No studies on the hydrolysis of 1H-perfluorohexane are available from the EU REACH registration dossier, as the information requirement was waived. However, the UK importer has provided a full study report to the Environment Agency as part of this evaluation. This has been reviewed, and limited details are presented below as the data contained in the report are not yet publicly available. The Environment Agency recommends that the EU Registrant updates their registration dossier accordingly.
A preliminary study was performed in accordance with OECD TG 111 (OECD, 2004) (hydrolysis as a function of pH) (Unpublished, 2020), where 1H-perfluorohexane was dosed with a co-solvent into buffer solutions at pH 4, 7 and 9. The nominal concentration of 1H-perfluorohexane in the buffers was below the water solubility limit (See Section 5.3). These solutions were maintained at 50 0.5 C for 120 hours. Sampling was performed in duplicate at 0 h, 24 h and 120 h. The pH of the sample solutions was also recorded at these sampling intervals. The concentration of 1H-perfluorohexane was measured using gas chromatography with flame ionisation.
Significant decreases in concentration were observed at all three pH values at 50 C (i.e. down to below 2% of the nominal starting concentration). As this was consistent across for all buffers, the pH was not considered to be a contributing factor. The study authors noted that due to the chemical structure of 1H-perfluorohexane hydrolysis should not occur. However, 1H-perfluorohexane is volatile and even with precautions taken to minimise losses during the study, it appears that the test item volatilised out of solution.
The report authors concluded that the main test could not be performed reliably due to the volatility of the test item, and hydrolysis at an environmentally pH and temperature is likely to be negligible.
The Environment Agency agrees that based on structural considerations, further investigation into hydrolysis is unnecessary.
Phototransformation in air
The EU REACH Registrant has presented non-GLP academically published data in the registration dossier for this endpoint. The study measured rate constants for the gas-phase reaction of 1H-perfluorohexane with hydroxyl (OH) radicals (Chen, 2003). The methodology
33 of 86
is equivalent to that presented for flash photolysis methods for absolute and relative rate determination in the OECD Guidance (OECD, 1992).
The absolute rate method involved kinetic measurements of hydroxyl radical concentrations in the presence of 1H-perfluorohexane using both flash photolysis-laser induced fluorescence (FP-LIF) and laser photolysis-laser induced fluorescence (LP-LIF) at 25 C. The absolute rate constant for the reaction of 1H-perfluorohexane with hydroxyl radicals was determined to be 1.71 (0.09) 10-15 cm3/molecule/s. Absolute methods can be subject to interference from hydroxyl radicals reacting with impurities or secondary reaction products. Approximately 80 repetitions of the experiments were performed to reduce variability and systematic error.
The relative rate method measured the disappearance of 1H-perfluorohexane and a reference compound (chlorodifluoromethane or 1,1-difluoroethane) in the presence of hydroxyl radicals at 25 C. Relative rate constants were calculated to be 1.87 (0.11) 1015 cm3/molecule/s or 2.12 (0.11) 10-15 cm3/molecule/s, depending on the reference compound.
Using these data, the rate constant for the reaction of 1H-perfluorohexane with hydroxyl radicals over the temperature range -23 to 157 C can be calculated from the following equation (scaled against data for 1,1,1-trichloroethane at -1 C):
Rate constant = (4.71 0.94) 10-13 exp[-(1630 80)/T] cm3/molecule/s
The tropospheric lifetime of 1H-perfluorohexane through reaction with hydroxyl radicals was estimated to be 31 years. The abstraction of the hydrogen atom by reaction with hydroxyl radicals is clearly very slow. For comparison, the carbon-fluorine chain is expected to be stable to direct photolysis for more than 1 000 years (Environment Canada, 2012). Although transformation products were not investigated, it is likely that a perfluoroalcohol (perfluorohexan-1-ol) was formed.
The EU REACH Registrant assessed this study to be reliable with restrictions (Klimisch 2) as it was well documented and followed generally accepted scientific principles, and the Environment Agency agrees with this rating.
For comparative purposes, the Environment Agency has considered readily available QSAR software to test how they perform for this type of substance. The US EPA CompTox dashboard contains a predicted atmospheric hydroxylation rate for 1H-perfluorohexane generated from the OPERA software (US EPA, 2020a). The predicted value is 3.94 x 10 -15 cm3/molecule/sec, which is slightly higher than the measured value. Structural analogues of 1H-perfluorohexane are included in the training set and so the substance is considered to be within the applicability domain of the model by CompTox. Following the method given in ECHA (2016), the Environment Agency calculates a rate constant for degradation in air of 0.00017 d-1, which equates to a half-life of 4 070 days (11 years), which is shorter than that derived from the measured value.
Commented [EL13]: Is this statement based on specific reference? Canada argued during POPRC14 that analogous 8 chain compound would be converted to perfluoroalcohol Do we want to add the same comments as Fluorocouncil did or ask that change to could be formed over long period of time, not was formed. "The FluoroCouncil argues that the intramolecular shielding of the H-C bond makes degradation extremely unlikely and that, in atmospheric conditions, the probability of a reaction with OH radicals is further reduced by the existence of a competing reaction with NOx that does not result in PFOA."
34 of 86
The RSC Chemspider portal contains a predicted atmospheric hydroxylation rate for 1H-perfluorohexane generated from the AOPWIN software (RSC, 2020a). The predicted value is 3 x 10-16 cm3/molecule/sec. Gomis et al. (2015) note that the predictive power of AOPWIN for PFAS is limited despite the inclusion of some fluorinated substances in the training set, and that based on comparisons of predicted and measured photodegradation rates for 7 fluorinated substances they expect that AOPWIN may underestimate the true half-life in air. However, the Environment Agency notes that this predicted reaction rate is lower (more conservative) than the measured value.
Phototransformation in water
No studies are available from the EU REACH registration dossier or from published data sources.
Phototransformation in soil
No studies on are available from the EU REACH registration dossier or from published data sources.
6.1.2 Biodegradation in water
Measured data
Table 6.1 Summary of screening biodegradation studies
Method OECD TG 301C (Ready Biodegradability: Modified MITI Test (I))
GLP
Results Not readily biodegradable
Approximately 6% degradation after 28 days based on BOD; Approximately 4% degradation after 28 days based on GC
Reliability Registrant: 1 (key study)
Reference Unpublished (1994a) cited in ECHA (2020a)
The biodegradation screening study in the EU REACH registration dossier is an OECD TG 301C (modified MITI) study carried out to GLP (Unpublished, 1994a; ECHA, 2020a). The inoculum used in the study was a mixture from a municipal sewage treatment plant, industrial sewage, surface waters and soil as specified in the test guideline. The sludge was not pre-adapted to the test material. Six test vessels were used: an abiotic control, a blank control, a positive control and three vessels with test substance and inoculum. Aniline was used as the positive reference substance. The test was carried out at a concentration of 100 mg/L of substance with 30 mg/L suspended solids over 28 days. As the test substance is volatile the test vessels were filled to minimise the amount of headspace. Degradation was monitored by measuring the Biological Oxygen Demand (BOD) and by direct measurement of the test substance concentration by GC analysis. Degradation of the test substance was found to be 6% based on BOD and 4% based on GC analysis, showing that the substance did not meet the criteria to be considered readily biodegradable. The degradation of aniline was found to reach 41% after 7 days and 95% after 14 days, which met the criteria to
35 of 86
demonstrate that the sludge was sufficiently active for the test to be valid. The EU REACH Registrant assessed this study to be reliable without restriction (Klimisch 1).
The Environment Agency found that the validity criteria were met and that this study followed the standards in OECD TG 301C. This guideline is considered suitable for testing substances which are volatile or poorly water soluble. The concentration of 1H-perfluorohexane used in this study was above the water solubility of 1.5 mg/L (Section 5.3). Following the test guideline, no solvent or emulsifying agent was used. However, no information is given on whether any other method was used to disperse the test material. The Environment Agency considers that the study is reliable and demonstrates that the substance did not meet the criteria to be considered readily biodegradable.
Predicted data
The US EPA CompTox dashboard contains a predicted biodegradation half-life of 4.08 days generated from the OPERA software (US EPA, 2020a), but notes that 1H-perfluorohexane is outside of the applicability domain of this model, so the prediction is not reliable.
The RSC Chemspider portal contains a prediction for the probability of rapid biodegradation for 1H-perfluorohexane generated from the BIOWIN software (RSC, 2020a). All seven BIOWIN models predict that 1H-perfluorohexane will not be readily biodegrade. The BIOWIN model predictions are based on the molecular fragments "carbons with four bonds that are not attached to hydrogens" and "trifluoromethyl group". The Environment Agency considers that these fragments describe 1H-perfluorohexane adequately and therefore that this substance is within the domain of these models.
Data from structural analogues
Analogues have not been considered as a suitable experimental study is available.
Discussion
The experimental data indicate that 1H-perfluorohexane is not readily biodegradable, as only low levels of removal (4 to 6%) were observed in a standard test designed to minimise volatile losses. Dissolution kinetics may have had some impact on the results as the study was performed well in excess of water solubility. The small amount of oxygen consumption and apparent loss of parent substance suggests slow transformation occurred. This is surprising, as carbon-fluorine bonds are expected to be very stable. Transformation products were not investigated. However, the hydrogen-bearing terminal carbon atom may have been partially oxidised to form a perfluoroalcohol (perfluorohexan-1-ol). This substance may well be stable, or it could potentially be slowly oxidised further to perfluorohexanoic acid.
6.1.3 Biodegradation in sediment
No studies are available from the EU REACH registration dossier or from published data sources.
36 of 86
Commented [MS14]: Noted, I agree that this is a reasonable hypothesis, but there is no evidence to support/contradict this. See comment from Edyta on PFOA.
6.1.4 Biodegradation in soil
No studies are available from the EU REACH registration dossier or from published data sources.
6.1.5 Summary and discussion on degradation
1H-Perfluorohexane is not expected to hydrolyse. Experimental information on its phototransformation potential in air, together with a QSAR prediction, indicates that it has a very long atmospheric half-life, estimated to be 31 years based on rate constant measurements.
A fully valid biodegradation screening study is available, indicating that the substance achieved a low level of removal (up to 6%) over 28 days. 1H-Perfluorohexane is therefore not readily biodegradable. Highly fluorinated substances generally do not undergo significant mineralisation under relevant environmental conditions. The screening biodegradation result is consistent with this. There are no environmental simulation data so a realistic half-life in aquatic or terrestrial media cannot be established.
Although the carbon-fluorine bond is very strong, a slow reaction occurred in both the photolysis and ready biodegradation tests. The transformation product(s) were not identified but are likely to include perfluorohexan-1-ol, which might in turn slowly oxidise further to perfluorohexanoic acid. The properties of these substances have not been considered for the purposes of this evaluation, although they are likely to be persistent.
6.2 Environmental distribution
6.2.1 Adsorption/desorption
Measured data
Adsorption/desorption of a chemical to solid phases is assessed using the organic carbon/water partition coefficient (KOC). The key experimental study in the EU REACH registration dossier was carried out according to OECD TG 121 (HPLC method) (OECD, 2001) and was GLP compliant (Unpublished, 2017a). The Environment Agency has reviewed the full study report.
This method was selected based on a QSAR prediction (see below), and used reverse phase UPLC at 35 C coupled to a refractive index detector, in conjunction with an isocratic mobile phase. 1H-Perfluorohexane does not contain functional groups that will dissociate and therefore the mobile phase was not buffered. Test and reference substances were analysed in duplicate. A single analysis was performed on the blank. It was verified that only one peak was observed in the chromatograms of the 1H-perfluorohexane solutions. The log KOC values of the reference substances ranged from 1.26 to 5.63, and these were used to generate a calibration curve using column capacity factors calculated from the substances' retention times. A log KOC of 3.7 was estimated for 1H-perfluorohexane using this curve.
37 of 86
Commented [MS15]: For 1H-perfluorohexane, ODP = 0, GWP = 2000.
Further experimental details provided in the study report are not presented in this evaluation as limited details are in the public domain.
The EU REACH Registrant considers the data to be reliable without restrictions (Klimisch 1), and the Environment Agency agrees that the study was well performed.
Predicted data
A preliminary calculation was performed using the Perrin calculation method (pKalc 5.0, module in Pallas 3.0, USA) as part of the HPLC study (Unpublished, 2017a). This is a fragment based method, and is recommended in the OECD test guideline. The log KOC of 1H-perfluorohexane was calculated to be 4.61. However, the study report does not provide any information about whether the training set and external test set contained similar substances, so its reliability cannot be established.
For comparative purposes, the Environment Agency has considered readily available QSAR software to test how they perform for this type of substance. The US EPA CompTox dashboard contains a predicted log KOC of 3.65 generated from the OPERA software (US EPA, 2020a), but notes that 1H-perfluorohexane is outside of the applicability domain of this model, so the prediction is not reliable.
The RSC Chemspider portal contains a predicted log KOC of 4.85 for 1H-perfluorohexane generated from the PCKOCWIN software (RSC, 2020). It is unclear whether this prediction is based on the Molecular Connectivity Index (MCI) method or on the log KOW method. If the latter, this value is unreliable, as it would have been based on a predicted log KOW value of 5.41. No information is available on substances in the training set and external test set, so no assessment of the applicability can be performed.
A log KOC of 3.42 can also be calculated based on the measured log KOW of 4.1 and the `predominantly hydrophobics' equation used in EUSES (v2.03). The Environment Agency notes that the applicability domain of this equation is unknown.
Data from structural analogues
Analogues have not been considered as a suitable experimental study is available.
Recommended value
A modern experimental study is available for 1H-perfluorohexane, which the EU REACH Registrant considers to be fully reliable. OECD TG 121 is a suitable method for testing volatile substances or those that are poorly water soluble, so was appropriate for 1H-perfluorohexane. However, the Environment Agency notes that the method is indirect, in that it uses the retention time on a HPLC column in comparison to a series of reference standards to provide an estimate of KOC. Highly fluorinated substances may have the potential to form separate phases from water and organic media, and this was not investigated as part of the study.
38 of 86
In the absence of a direct measurement, the experimentally determined log KOC value of 3.7 will be used for the purpose of this evaluation. This value suggests that the substance is likely to bind to soil and sediment to a moderate extent.
6.2.2 Volatilisation
Measured data
There is no relevant information in the EU REACH registration dossier. A measured value of 33 atm.m/mol (3.34 x 106 Pa.m/mol) is reported in the experimental database of the HENRYWIN v3.1 module of the EPISuiteTM estimation programme. No further details are provided, so the reliability of this information is unknown.
Predicted data
There is no relevant information is available in the EU REACH registration dossier.
The Environment Agency has calculated a Henry's Law constant (HLC) using EUSES (v2.03). The US EPA CompTox dashboard and ChemSpider database also contained predicted HLC values for 1H-perfluorohexane generated from OPERA software (RSC, 2020a, US EPA, 2020a). These values are presented in Table 6.2. The Environment Agency has converted the values from atm.m/mol to Pa.m/mol.
Table 6.2 Predicted Henry's Law constant for 1H-perfluorohexane
Source EPISuiteTM
Details Bond Method: 1.27 x 102 atm.m/mol
Estimation programme
HENRYWIN v3.1 OPERA
Group Method: 2.45 x 101 atm.m/mol Vapour pressure/water solubility estimate using EPISuiteTM derived values: 9.554 atm.m/mol
Predicted value: 6.8 x 10-2 atm.m/mol
Global applicability domain: outside
Local Applicability domain index: 0.278
EUSES v2.03
Confidence Interval: 0.357
Calculated from the measured water solubility of 1.5 mg/L at 20 C and vapour pressure of 15 kPa at 20 C
HLC (Pa.m/mol) 1.29 x 107 2.48 x 106 9.68 x 105 6.89 x 103
4.22 x 106
In silico predicted values should always be treated with caution where substances in the training set and external test set are not visible.
For the HENRYWIN model, the training and validation sets contained several PFCs (see Appendix B) and it is likely that the predicted value for 1H-perfluorohexane falls within the applicability domain of the model. However, the prediction relies on predicted values for vapour pressure and water solubility, so the output should be treated with additional caution.
39 of 86
No close structural analogues of 1H-perfluorohexane were included in either the training set or external test sets of the OPERA model. 1H-Perfluorohexane is considered to be outside the global applicability domain and has a low local applicability domain index (< 0.4), so the prediction is not considered reliable based on the OPERA model applicability domain criteria.
The equation in EUSES is a simple relationship between a substance's vapour pressure and water solubility, and is a suitable estimate although it does not necessarily reflect actual partitioning behaviour in a steady state system.
Data from structural analogues
There is no information for relevant analogues.
Recommended value
The Environment Agency recommends a HLC of 4.22 x 106 Pa.m3/mol for modelling purposes calculated from the preferred water solubility value and vapour pressure. This is similar to a reported measured value of unknown reliability (3.34 x 106 Pa.m/mol). This value suggests that the substance will readily volatilise from water to air.
This value has been used to derive a dimensionless HLC or air-water partition coefficient (log KAW) of 3.25, which is used in the prediction of long-range transport (see Section 6.3).
6.2.3 Distribution modelling
The Environment Agency has used the SIMPLETREAT model in EUSES (v2.03) to predict the partitioning of 1H-perfluorohexane in a wastewater treatment plant based on its lack of ready biodegradability, reported KOC and vapour pressure, as follows:
Air: 68.6%
Water: 4.01%
Sludge: 27.4% This model predicts that a significant fraction will partition to the atmosphere. The reliability of this model for this type of substance is unknown, and the uncertainties in the physicochemical input parameters also mean that this distribution might not be fully reliable.
6.3 Long range transport potential
The OECD has produced a decision support tool for estimating the long-range transport potential (LRTP) of organic chemicals at a screening level (Wegmann et al., 2009). It is a steady state non-equilibrium model in a standardised evaluative environment, and predicts three characteristics that can be used to provide an indication of the LRTP of a substance: Characteristic Travel Distance, Transfer Efficiency and overall persistence (POV).
40 of 86
To estimate the LRTP of 1H-perfluorohexane, the Environment Agency has performed calculations using the input parameters indicated in
Table 6.3.
Table 6.3 Estimated long range transport potential of 1H-perfluorohexane
Input Parameter
Value
Molecular mass
320.05 g/mol
Log Kaw a
3.25
Log KOW
4.1
Half-life in air (hours)b
271 560
Half-life in water (hours)c
2.1 x 1041
Half-life in soil (hours)c
2.1 x 1041
LRTP output parameter
Characteristic Travel Distance (km)
1 089 330
Transfer Efficiency (%)
679
POV (days)
17 044
Note: a - This is the log of the dimensionless HLC calculated using Equation R.16-5 of ECHA R16. b - This is a measured half-life. c - The upper bound value for biodegradation of a non-readily biodegradable substance in EUSES is 1 x 1040 days to represent infinity (equivalent to 2.1 x 1041 hours).
The OECD LRTP screening tool allows comparisons of these three characteristics for a range of substances, provided in
Figure 6.1.
Figure 6.1 Long range transport potential of 1H-perfluorohexane
Commented [MS16]: These seem excessively high. Is it scientifically justifiable for the half-life in water and soil to be 40 orders of magnitude higher than the half-life in air? How do these half-lives account for evaporation given the volatility of this substance? Persistent does not equal permanent. Commented [MS17]: Theoretical values not science based.
Commented [MS18]: As noted above, this value seems excessively high. 1 x 108 represents a half-life of more than 10,000 years. What impact on the model does using this value make? Note this is an arbitrary number to see the impact on the model and although not scientifically justified, in my opinion, could be more representative of reality.
41 of 86
Based on this screening tool, it appears that 1H-perfluorohexane may be capable of long range transport. . Evidence of occurrence (or not) of 1H-perfluorohexane in the Arctic and other remote regions also needs to be taken into account (noting the proximity of industrial activity and population centres). This is beyond the scope of this evaluation.
6.4 Bioaccumulation
6.4.1 Bioaccumulation in aquatic organisms
Measured data
Table 6.4 Method
Summary of bioaccumulation studies
Results
Reliability
Reference
OECD TG 305C GLP
Cyprinus carpio BCF 293 to 615 after exposure to 50 g/L
Cyprinus carpio BCF 336 to 658 after exposure to 5 g/L
Registrant: 1 (key study)
Unpublished (1994b) cited in ECHA (2020)
The bioaccumulation study in the EU REACH registration dossier is an OECD TG 305C (OECD, 1981) study carried out to GLP using Carp (Cyprinus carpio) (Unpublished, 1994b; ECHA, 2020a). The test material was not radiolabelled. Test solutions were prepared by preparing a 10:1 solution of the test substance with the solvent MEGAFAC F-142D, before this was diluted with ion-exchanged water to produce stock solutions with nominal concentrations of 20 mg/L and 2 mg/L. The final test solutions had a nominal exposure concentration of 50 and 5 g/L and the study was conducted using a flow-through exposure for 8 weeks. There was no depuration phase. The concentration of the solvent in the final test solution is not stated. Twelve fish (age not stated) were exposed to each exposure concentration, and five fish were used as a control. Test substance concentrations in the exposure media were analysed by GC/FID twice a week. Two fish were sampled in weeks 2, 4, 6 and 8. Sampled fish were weighed and measured before the concentration of test compound was determined by GC/FID. Lipid content of the fish was not measured. Control fish were only sampled at the beginning and end of the 8 week period.
Other than the flow through exposure system, no further information is given on measures taken to limit losses due to volatilisation. However, mean measured exposure concentrations ranged from 48.4 to 50.5 g/L at the higher exposure level, and 4.37 to 4.56 g/L at the lower exposure level, and it is stated that each average concentration was maintained at >90% nominal.
This study was conducted to a guideline that has since been superseded, so no depuration phase was included although the uptake phase of 8 weeks is longer than required by the
42 of 86
Commented [MS19]: Has it been looked for (do not believe so)?
current test guideline (OECD, 2012). The fish bioconcentration factors (BCF) were calculated for each two-week sampling period, and it is unclear whether steady state was reached during this study (Figure 6.2). For both exposure concentrations, BCF initially increased with the highest BCF observed during the fourth week of exposure. In three of the replicates, BCF decreased in week 6, before increasing in week 8 but not to the levels reported in week 4 (see Figure 6.2). The BCF was reported to range from around 300 to 660 at both exposure concentrations. The EU REACH Registrant gave the study a Klimisch score of 1 (reliable without restriction).
Figure 6.2 BCF over time (weeks) for each replicate
BCF
700
600
500
400
300
200
100
0
0
1
2
3
4
5
6
7
8
weeks
50 g/L replicate 1 5 g/L replicate 1
50 g/L replicate 2 5 g/L replicate 2
The Environment Agency considers that this study is of unknown reliability (Klimisch 4). The number of fish used in this study is considerably lower than that of the updated OECD TG 305, and the lack of information on growth and lipid content of the fish over the 8-week study period adds to the uncertainty. The variation in fish concentration during the test makes it questionable whether steady state was actually reached, even though it appears that a plateau was being approached. BCF reported on the last 3 sampling occasions (weeks 4, 6 and 8) were within 20% of each other for all treatments except for replicate 2 at 5 g/L (77% of average BCF at week 6), compared to the most recent TG requiring concentrations in fish to be within 20% of each other over three successive samples for steady state to have been reached. There is no depuration period so it is not possible to calculate a kinetic BCF.
Predicted data
The US EPA CompTox dashboard contains predicted fish BCF values for 1H-perfluorohexane generated from both the T.E.S.T. and OPERA software (US EPA, 2020a). The OPERA model predicts a BCF of 300, but notes that 1H-perfluorohexane is outside of the applicability domain of this model, so the prediction is not valid. The T.E.S.T.
Commented [DF20]: One view might be that the study should be repeated although, in my view, this is unnecessary for technical reasons.
Commented [MS21R20]: This value is important and affects the environmental classification. Using this data is very precautious to classify (threshold BCF > 500).
Commented [MS22R20]: AGCCE view is that this study has a higher reliability - would concede Klimisch 2 rather than 1. It looks like the EA have taken the worst case value from the study. Our view is that the mean value would be more appropriate.
43 of 86
model predicts a BCF of 483, and structural analogues of 1H-perfluorohexane are included in the training set so this value might be more reliable.
The RSC Chemspider portal contains a predicted BCF of 2 930 for 1H-perfluorohexane generated from the BCFWIN software (RSC, 2020a). However, this value is based on a predicted log KOW of 5.41, so is not considered reliable for use in this assessment.
A BCF can also be calculated based on the log KOW and the equation in ECHA (2017c). The Environment Agency has used the experimental log KOW of 4.1 to calculate a BCF of 610. This is in good agreement with the highest reported measured BCF.
Data from structural analogues
Analogues have not been considered given the apparent agreement between measured and predicted BCF.
Recommended value
The experimental data provided in the EU REACH registration indicates a maximum fish BCF of 658. This is consistent with predicted BCF from two QSARs. Although neither the experimental study nor predicted values are fully reliable, together they indicate that the potential for aquatic bioaccumulation may be moderate. The highest BCF from the experimental study will be used for the purposes of this assessment.
6.4.2 Terrestrial bioaccumulation
The EU REACH Registrant has not assessed the potential for terrestrial bioaccumulation as this is not an information requirement at the current level of supply.
Evidence from other highly fluorinated substances suggests that terrestrial bioaccumulation may be more relevant for this type of substance than aquatic bioaccumulation, although this is mainly related to the ability of some PFAS (particularly perfluorocarboxylic acids) to bind to proteins.
In terms of bioaccumulation in air breathing organisms, the screening criteria are log KOW > 2 and log KOA > 5 (ECHA, 2017c). Although the log KOW (4.1) exceeds the threshold the log KOA (3.7) does not, so this criterion is not met.
No information on bioaccumulation is available from the available mammalian toxicity studies.
6.4.3 Summary and discussion of bioaccumulation
Taken together, the results from the OECD TG 305 study (BCF 658) and the predicted values from two QSAR models that are considered valid (BCF 483 to 610) indicate that the substance can be considered to be moderately bioaccumulative in aquatic gill-breathing organisms as the BCF exceeds 500. The substance does not meet the screening criteria for terrestrial bioaccumulation.
44 of 86
45 of 86
7 Ecotoxicology
7.1 Aquatic compartment
The same comments about sources of data, reliability scoring and use of supplemental information apply as for Section 5.
7.1.1 Fish
Short-term (acute) toxicity
Table 7.1 Method
Summary of acute toxicity to fish
Species
Analytical method
Results
Reliability
Reference
JIS K 01021986-71
(semi-static)
Japanese Medaka
Oryzias latipes
None
Limit test
48-h LC50 >125 mg/L (nominal)
Registrant: 2 (key study)
Unpublished (1994b) cited in ECHA (2020)
GLP
The acute fish toxicity study in the EU REACH registration dossier is a Japanese Industrial Standard JIS K 0102-1986-71 guideline study carried out to GLP using Japanese Medaka (Oryzias latipes) (Unpublished, 1994b; ECHA, 2020). This study was conducted as a semistatic limit test. Test solutions were prepared by preparing a 10:1 solution of the test substance with the solvent MEGAFAC F-142D, which was then diluted with ion-exchanged water to produce a stock solution with a nominal concentration of 1 000 mg/L. The final test solution had a nominal concentration of 125 mg/L and renewal was conducted every 8 to 16 hours. The concentration of the solvent in the final test solution is not stated. Ten fish were exposed to the test substance and a control. As no mortality was observed in this limit test, the 48-h LC50 was reported to be >125 mg/L based on nominal concentrations. The EU REACH Registrant gave the study a Klimisch score of 2 (reliable with restriction).
The validity criteria were not stated in the study report or registration dossier. In addition, it is not stated whether the control is a blank control or a vehicle control. However, the Environment Agency considers that as no mortality was observed in the control or exposure vessels this suggests that the conditions of the test were appropriate.
The water solubility of this substance is 1.5 mg/L (Section 5.3). A solvent was used to produce a test solution far in excess of the water solubility, but no chemical analysis was undertaken to confirm the exposure concentration and the concentration of solvent is not stated. It is therefore unclear what concentration of the test substance and solvent the fish
46 of 86
were exposed to. As the test substance is volatile it is likely that the actual concentrations of the test substance to which the fish were exposed were lower than the nominal value despite regular test medium renewal.
Overall, this study suggests that the substance has a low acute toxicity to fish over 48 hours, with no effects up to the limit of solubility in the test medium, although the exposure concentration was not confirmed by analysis. However, as this exposure duration is shorter than the standard 96 hours, this result should be treated with caution and only used if supported by other data (e.g. read across, QSAR, etc.) (ECHA, 2017b).
The Environment Agency has generated a predicted acute fish 96 hour LC50 using ECOSAR v1.11 (US EPA, 2012) and inputting a water solubility of 1.5 mg/L and a log KOW of 4.1. This model predicts that acute toxicity will not be observed at the limit of solubility. It is recommended that the EU REACH Registrant uses ECHA's Read-Across Assessment Framework (RAAF) (ECHA, 2017d) to provide additional supporting information for this endpoint.
Long-term (chronic toxicity)
Long-term toxicity tests on fish are not available. This is not a standard REACH information requirement at the current level of supply.
7.1.2 Aquatic invertebrates
Short-term (acute) toxicity
Table 7.2 Method
Summary of acute toxicity to aquatic invertebrates
Species
Analytical method
Results
Reliability
Reference
OECD TG 202
(static)
Daphnia magna
GC-MS
GLP
48-h EC50 >1.1 mg/L (measured initial); mobility end point
Registrant: 1 (key study)
Unpublished (2017b) cited in ECHA (2020)
The acute aquatic invertebrate toxicity study in the EU REACH registration dossier is an OECD TG 202 study carried out to GLP using the water flea Daphnia magna (Unpublished, 2017b; ECHA, 2020). Test solutions were prepared by slow stirring a 100 mg/L loading of test substance in M7 test medium in a closed vessel for one day by magnetic stirrer. The resulting mixture was allowed to settle for one hour before the clear and colourless saturated solution was siphoned out of the vessel and used as the highest (100%) test concentration. Lower test concentrations of 10%, 1% and 0.1% were prepared by dilution of the saturated solution. The test was conducted in sealed glass vessels that were filled so that there was
47 of 86
no headspace. Chemical analysis of the 10% and 100% exposure concentrations showed that the initial measured exposure concentrations were 0.089 mg/L and 1.1 mg/L respectively and that these remained within 20% for the duration of the test. Analysis of the lower exposure concentrations and blank control found that the concentrations were below the limit of detection (0.008 mg/L) at all times. Twenty daphnids were exposed to the control and 100% saturated solution, with ten daphnids being exposed to the remaining test concentrations. Only a single daphnid became immobilised in this test, at the highest exposure concentration. Therefore, the 48-h EC50 based on immobilisation was reported to be >1.1 mg/L expressed as the initial measured concentration. The EU REACH Registrant gave the study a Klimisch score of 1 (reliable without restriction).
The validity criteria for <10% immobility in the controls and 3 mg/L dissolved oxygen (DO) were met. Actual concentrations of the test substance were verified to be within 80 and 120% of the initial measured concentration at the highest two test concentrations, and the maximum exposure concentration achieved is similar to the water solubility of the test substance (1.5 mg/L, Section 5.3). All other test parameters followed the standards in OECD TG 202, and measures were taken to minimise volatile losses. Therefore, the Environment Agency considers that the study is reliable for the purposes of this assessment.
Overall, the data indicate that the substance has a low acute toxicity to aquatic invertebrates as effects were not observed when using a saturated solution.
The Environment Agency has generated a predicted acute invertebrate 48 hour EC50 using ECOSAR v1.11 (US EPA, 2012) and inputting a water solubility of 1.5 mg/L and a log KOW of 4.1. This model predicts that acute toxicity will not be observed at the limit of solubility. It is recommended that the EU REACH Registrant uses ECHA's Read-Across Assessment Framework (RAAF) (ECHA, 2017d) to provide additional supporting information for this endpoint.
Long-term (chronic) toxicity
Long-term toxicity tests on aquatic invertebrates are not available. This is not a standard REACH information requirement at the current level of supply.
7.1.3 Algae and aquatic plants
Table 7.3 Method
Summary of toxicity to algae
Species
Analytical method
Results
Reliability
Reference
OECD TG 201
(static)
Pseudokirchneriella subspicata
GC-MS
72-h ErC50 >0.098 mg/L (measured TWA)
Registrant: 1 (key study)
Unpublished (2017c) cited in ECHA (2020)
48 of 86
GLP
72-h EyC50 >0.098 mg/L (measured TWA)
72-h NOErC 0.098 mg/L (measured TWA)
72-h NOEyC 0.098 mg/L (measured TWA)
The algal growth inhibition study in the EU REACH registration dossier is an OECD TG 201 study carried out to GLP using Pseudokirchneriella subcapitata (Unpublished, 2017c; ECHA, 2020). Test solutions were prepared by slow stirring a 100 mg/L loading of test substance in adjusted M2 test medium for one day in a closed vessel by magnetic stirrer. The resulting mixture was allowed to settle for one hour before the clear and colourless saturated solution was siphoned out of the vessel and used as the highest (100%) test concentration. Lower test concentrations of 10%, 1% and 0.1% were prepared by dilution of the saturated solution. The test was conducted in sealed glass vessels that were filled so that there was no headspace. Chemical analysis of the 10% and 100% exposure concentrations showed that the initial measured exposure concentrations were 0.047 mg/L and 0.72 mg/L respectively. Analysis showed that exposure concentrations reduced over the exposure period, such that at 24 hours the 10% exposure concentration was below the limit of detection and the 100% exposure concentration had reduced to 13% of the initial measured concentration. At 72 hours, the 100% exposure concentration was below the limit of detection. Analysis of the lower exposure concentrations and blank control found that the concentrations were below the limit of detection (0.008 mg/L) at all times.
The study authors report that no statistical analysis of the data was performed as results were similar in the control and highest test concentration. The 72-h EC50 based on growth rate and yield were reported to be >0.098 mg/L expressed as a measured time weighted average (TWA) concentration (in accordance with OECD TG 201). The 72-h NOEC based on growth rate and yield were reported be 0.098 mg/L expressed as a measured TWA concentration. The EU REACH Registrant gave the study a Klimisch score of 1 (reliable without restriction).
All the validity criteria were met. The results were not statistically analysed by the report authors to determine the NOEC. However, as the highest exposure concentration resulted in a 0.6% increase in growth rate and a 2.2% increase to yield the Environment Agency agrees that no adverse effects were observed in this study.
Although measures were taken to minimise volatile losses, actual concentrations of the test substance could not be maintained within 20% of the initial concentration. A similar decrease in exposure concentration was observed in duplicate test vessels without algae, indicating that the loss of test substance was independent of the presence of algal cells. It is unclear why the maximum exposure concentrations achieved in this study were lower and
49 of 86
Commented [DF23]: The lab have confirmed that there was, in fact, a small headspace.
Commented [MS24R23]: The presence of a headspace may affect the 1H-perfluorohexane concentration in the aqueous phase. For the algal study, samples are withdrawn by syringe during the study so the headspace increases during the study period.
decreased more rapidly than those in the acute invertebrate study which was conducted at the same laboratory. Both studies used the same method to prepare the test media and both were conducted in sealed test vessels with no headspace.
All other test parameters followed the standards in OECD TG 201 and the study took steps to achieve the maximum possible exposure concentration. The Environment Agency considers the use of a TWA to derive the NOEC is precautionary in this case.
Overall, the data suggest that the substance has a low toxicity to algae for both short- and long-term endpoints as effects were not observed when using a saturated solution, although the significant decline in test concentration confounds the interpretation of this study.
The Environment Agency has generated a predicted acute algal 96 hour EC50 and a chronic effect value using ECOSAR v1.11 (US EPA, 2012) and inputting a water solubility of 1.5 mg/L and a log KOW of 4.1. This model predicts that acute and chronic toxicity will not be observed at the limit of solubility. It is recommended that the EU REACH Registrant uses ECHA's Read-Across Assessment Framework (RAAF) (ECHA, 2017d) to provide additional supporting information for this endpoint.
No toxicity data are available for higher aquatic plants, although this is not a standard REACH information requirement at the current level of supply.
7.1.4 Sediment organisms
No relevant information is available in the EU REACH registration dossier. This is not a standard REACH information requirement at the current level of supply.
7.1.5 Other aquatic organisms
No other relevant information is available
7.2 Terrestrial compartment
No relevant information is available in the EU REACH registration dossier. This is not a standard REACH information requirement at the current level of supply.
7.3 Microbiological activity in sewage treatment systems
Table 7.4 Summary of toxicity to sewage microorganisms
Method
Analytical method
Results
Reliability
Reference
Commented [MS25]: There was a headspace in the vials used in the algae study.
Commented [MS26]: Some detail: the volume of the vials used for the algae test is 120 ml. The volume of each sample taken for analyses is 2.0 ml. Samples are taken on three occasions. Additional smaller samples (0.1 ml from 100% SS; 1.0 ml from 10% SS) were taken at the start of the study. So, for the 100% SS vials, the headspaces went from 2.1 ml at t=0 to 4.1 ml at t=24 hr, then 6.1 ml at 48 hr and, finally, 8.1 ml at t=72 hr. The final analysed concentration will reflect that concentration in solution with a prevailing headspace of 6.1 ml.. (from DGF discussion with CRL, email 25/11/21).
50 of 86
OECD TG 209 (static)
None
GLP
Combined limit/range finding test
Registrant: 1 (key study)
3-h ELR50 >1 000 mg/L (nominal)
3-h NOELR not determined
Unpublished (2017d) cited in ECHA (2020)
The key study in the EU REACH registration dossier is an OECD TG 209 study carried out to GLP (Unpublished, 2017d; ECHA, 2020). The test was conducted using activated sludge from a sewage treatment plant receiving predominantly domestic sewage. Due to the volatility and low solubility of the test substance, a stock solution was not prepared, and instead the test substance was added directly to the test vessels at three nominal loading rates (10, 100 and 1 000 mg/L) with single replicates at the lower two concentrations and three replicates at the highest loading rate. The test is described as a combined limit/rangefinding test, and there was no analytical measurement of the exposure concentration as this is not required by the guideline when the test substance is added directly to the test vessels. Blank, reference compound, abiotic and nitrification controls were also included. At the end of the study the 10, 100 and 1 000 mg/L loading rates inhibited the respiration rate by 10, 6 and 14% respectively. The 3-h ELR50 could not be calculated as there were no effects above 50%. The highest loading rate was found to have a significant effect on respiration rate, but a NOELR could not be determined with confidence (it would lie in the range 100 to 1 000 mg/L (nominal)). The 3-h EC50 based on sludge respiration in the positive control with 3,5-dichlorophenol fell within the expected range and all other validity criteria were met. The EU REACH Registrant gave the study a Klimisch score of 1 (reliable without restriction).
The Environment Agency also considers that all test parameters followed the standards in OECD TG 209 and that this study is sufficient to demonstrate that the 3-h ELR50 is above the highest tested nominal loading rate of 1 000 mg/L. A NOELR could not be defined but was below the maximum nominal loading rate of 1 000 mg/L.
Overall, the available test indicates that the substance is not acutely toxic to sewage microbes at loading rates up to 1 000 mg/L.
7.4 Atmospheric effects
The Henry's Law constant indicates that 1H-perfluorohexane is likely to significantly partition to air (see Section 6.2.2). No data about biotic effects from aerial exposure are available in the EU REACH registration dossier (ECHA, 2020), but this is not a standard information requirement.
The available data in the EU REACH registration dossier suggest that 1H-perfluorohexane is unreactive to ozone, and therefore is unlikely to be an ozone depleting substance.
51 of 86
PFCs are known to be potent greenhouse gases, and this is considered further in Section 9.5.
52 of 86
8 Mammalian toxicology
The following information is taken directly from the ECHA public dissemination website entry for 1H-perfluorohexane (ECHA, 2020a). The focus is on those mammalian endpoints which are potentially relevant for determination of the substance as Toxic (`T') according to the REACH Annex XIII criteria (see Section 9.3) or for a wildlife secondary poising assessment (see Section 9.6). No acute data are included and no human health hazard assessment has been undertaken. The study details and their reliability (Klimisch) scores are as presented by the EU REACH Registrant and the Environment Agency has not evaluated this information.
8.1 Toxicokinetics
No information is available in the EU REACH registration dossier.
8.2 Repeated dose toxicity
Table 8.1 Method
Summary of mammalian repeated dose toxicity endpoints
Species
Brief details
study Results
Reliability (Klimisch) score
Reference
Repeated
Rat
dose oral
toxicity,
OECD TG
421 + EPA
OPPTS
870.3550
GLP
Administered via oral gavage at nominal 0, 100, 300 and 1 000 mg/kg bw/day test article for 29 days in males, 50 to 64 days in females that delivered and 43 to 53 days in females that failed to deliver healthy offspring.
NOAEL 1 000 mg/kg/day (nominal); systemic toxicity.
No adverse treatment-related effects on mortality, clinical appearance, body weight and body weight gain, food consumption were observed.
Registrant: 1 (key study)
Unpublished (2017e) cited in ECHA (2020a)
Commented [DF27]: We have included some QSAR assessments in the "Hazard Assessment" Report that we shared with the ECHA (PFHxA consultation): Currently, no bespoke study exists for the toxicokinetics of 1Hperfluorohexane. Some assumptions can be made about aspects of the toxicokinetics from existing data. The results of repeated-dose oral toxicity studies show that the substance is absorbed by the gastrointestinal tract to some extent. The low water solubility and high partition coefficient suggest that blood levels are likely to be low and that it is likely to accumulate in lipophilic tissues. Based on its chemical structure, it is unlikely that the substance will be extensively metabolised.
53 of 86
Method
Species
Brief details
study Results
Reliability (Klimisch) score
Reference
Repeated
Rat
dose oral
toxicity,
OECD TG
407, 28-day
GLP
Administered via oral gavage at nominal 0, 40, 200 and 1 000 mg/kg bw/day test article for 28 days followed by a 14 day recovery period.
NOEL 200 mg/kg bw/day (nominal); organ weights and organ / body weight ratios.
Increased liver weights were observed in male rats exposed to the test material at 1 000 mg/kg/day. No histopathological changes were observed in the liver.
Registrant: 1 (key study)
Unpublished (1994c) cited in ECHA (2020a)
8.3 Mutagenicity
Three in-vitro genetic toxicity studies are included in the EU REACH registration dossier.
Table 8.2 Method
Summary of mammalian mutagenicity endpoints
Species
Brief study details
Results
Reliability (Klimisch) score
Reference
Bacterial reverse mutation assay,
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Salmonella typhimurium
and Escherichia coli
Exposure at 0, 313, 625, 1 250, 2 500, or 5 000 g/plate (nominal)
Negative (no adverse effects reported at these concentrations)
The substance has no reverse mutagenic potential under the study conditions.
Registrant: 1 (key study)
Unpublished (1994d) cited in ECHA (2020a)
GLP
54 of 86
Method
Species
Brief study details
Results
Reliability (Klimisch) score
Reference
Mammalian cell micronucleus test, JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Chinese hamster lung fibroblast cells
GLP
Exposure of cell plates at nominal concentrations of 0, 12.5, 25, and 50 g/mL for 24 hours, 0, 25, 50, and 100 g/mL for 48 hours and 0, 1 250, 2 500, and 5 000 g/mL for the metabolic activation method.
The substance did not induce chromosome aberrations in the absence or presence of metabolic activation.
Registrant: 2 (key study)
Unpublished (1994e) cited in ECHA (2020a)
Mammalian cell gene mutation test using the thymidine kinase gene, OECD TG 490
Mouse lymphoma L5178Y cells
GLP
Exposure of cell plates at 0.05, 0.17, 0.54, 1.7, 5.4, 17, 52, 164 g/mL (nominal)
No significant increase in the mutation frequency was observed in the presence or absence of metabolic activation
Registrant: 1 (key study)
The substance is not mutagenic in the TK mutation test system.
Unpublished (2016) cited in ECHA (2020a)
8.4 Carcinogenicity
No information is available in the EU REACH registration dossier.
55 of 86
8.5 Toxicity to reproduction (effects on fertility and developmental toxicity)
Table 8.3 Method
Summary of mammalian reproductive toxicity endpoints
Species
Brief study details
Results
Reliability (Klimisch) score
Reference
Reproduction / Rat developmental toxicity screening test, OECD TG 421 + EPA OPPTS 870.3550
GLP
Administered via oral gavage at 0, 100, 300 and 1 000 mg/kg bw/day (nominal) for 29 days in males, 50 to 64 days in females that delivered and 43 to 53 days in females that failed to deliver.
NOAEL: 1 000 mg/kg bw/day; systemic toxicity in the first parental generation and reproductive and developmental toxicity in the F1 generation.
No adverse treatmentrelated effects on mortality, clinical appearance, body weight and body weight gain, food consumption were observed.
Registrant: 1 (key study)
Unpublished (2017f) cited in ECHA (2020a)
8.6 Summary of mammalian toxicology
Based on the available mammalian toxicology data, the EU REACH Registrant concludes that no effects were demonstrated in studies conducted at maximally attainable vapour concentrations, limit doses, or other limits imposed by safety considerations.
56 of 86
9 Environmental hazard assessment
9.1 Classification and labelling
9.1.1 Harmonised classification
There is no current entry in Annex VI of the Classification, Labelling and Packaging (CLP) Regulation (EC) No 1272/2008.
9.1.2 Self-classification
The EU REACH registration dossier proposes that the substance is Not Classified.
ECHA's Classification and Labelling (C&L) Inventory of aggregated self-classifications includes the hazard classes listed below (ECHA, 2020b):
- Skin Irrit. 2 (H315)
- Eye Irrit. 2 (H319)
- STOT SE 3 (H335)
9.1.3 Conclusions for classification and labelling
1H-Perfluorohexane is not readily biodegradable and there is no evidence that it degrades significantly via abiotic mechanisms in aquatic media (see Section 7.1). It is therefore considered to be "not rapidly degradable" for the purposes of hazard classification.
The highest reported experimental fish BCF value is 658, which is consistent with predicted values (see Section 7.3). Despite the limited reliability of the fish bioconcentration study, 1H-perfluorohexane meets the bioaccumulation criterion for the purposes of hazard classification, since both experimental and predicted BCF values exceed 500 L/kg (the log KOW also exceeds 4).
Acute ecotoxicity endpoints are available for fish, invertebrates and algae (see Section 8). No toxic effects were observed in acute studies for invertebrates and algae at the practical limit of solubility in the test media, although measured concentrations declined inexplicably in the algal test, resulting in a 72-h ErC50 >0.098 mg/L based on TWA. A 48-h LC50 of >125 mg/L (nominal) was obtained for fish, which can be interpreted as showing no effects at the practical limit of solubility in the test medium, although the test duration was shorter than normal, and losses of test substance due to volatilisation cannot be ruled out. A conservative approach would be to use the algal ErC50 at face value. However, since no acute toxic effects were reported in any test and predicted ecotoxicity values also indicate that acute effects would not be anticipated up to the limit of solubility, the Environment Agency considers that
Commented [MS28]: This is not consistent with AGCCE's classification or that on the ECHA website. See AGCCE SDS (attached) and ECHA links below.
Commented [MS29R28]: ECHA website notes: Hazard classification & labelling There is no harmonised classification and there are no notified hazards by manufacturers, importers or downstream users for this substance. Substance Information - ECHA (europa.eu) and Registration Dossier - ECHA (europa.eu)
The link to reference ECHA, 2020b does not work - please share this information as this does not seem to be consistent with what AGCCE has submitted to ECHA or what AGCCE can find on the ECHA website.
I note the classification reported in this document is the same as that for 1H-perfluorohexane-1,1-diol (CAS 754-79-0): Substance Information - ECHA (europa.eu) and C&L Inventory (europa.eu)
57 of 86
this would be too precautionary, and so Aquatic Acute classification is not required. This is consistent with the EU REACH Registrant's view.
Chronic aquatic toxicity data are not available for fish or invertebrates. No adverse chronic effects were observed in the algal toxicity test, resulting in a 72-h NOErC of 0.098 mg/L based on TWA, and chronic effects on algae were not predicted up to the limit of solubility. As the substance is not rapidly degradable, a NOEC in the range 0.01 to 0.1 mg/L would lead to classification as Aquatic Chronic 1 (with a multiplication (M-)factor of 1). This would be a conservative conclusion given the lack of effects, but could be warranted by the rapid decline in test concentration. The Environment Agency notes that in the absence of further long-term toxicity information for fish and invertebrates, classification as Aquatic Chronic 4 is a minimum requirement because the substance is poorly water soluble, not rapidly degradable and BCF values are 500. The Environment Agency recommends that the UK importer updates their self-classification to reflect these findings.
The human health hazard classification has not been considered.
9.2 Assessment of endocrine disrupting (ED) properties
The ecotoxicity dataset does not include any studies that assess ED potential and no additional information was identified during the literature search (Appendix A).
9.3 PBT and vPvB assessment
Persistence: No environmental half-life data are available for comparison with the definitive criteria in REACH Annex XIII. 1H-Perfluorohexane is not readily biodegradable and there is no evidence that it degrades significantly via abiotic mechanisms in aquatic media (see Section 6.1). It therefore meets the screening criterion for being potentially persistent (P) or very persistent (vP). The EU REACH registration dossier concludes that the substance is vP (and P) based on the ready biodegradability study.
Bioaccumulation: 1H-Perfluorohexane has a reported log KOW of 4.1 (see Section 5.4), which does not meet the screening criterion for bioaccumulation (`B') (as it is <4.5). Although there are some uncertainties in the reported fish BCF (see Section 6.4), the maximum value (658) is also significantly below the definitive bioaccumulation (`B') criterion in REACH Annex XIII (>2 000 L/kg).
In terms of bioaccumulation in air-breathing organisms, the log KOW meets the screening criteria (>2) but the log KOA of 0.85 does not (as it is <5).
The EU REACH registration dossier considers that 1H-perfluorohexane does not fulfil the criteria for `B' based on the fish BCF values.
Toxicity: In terms of aquatic toxicity, a 72-h NOErC of 0.098 mg/L is available for algae, which does not meet the REACH Annex XIII criterion for toxicity (T) of <0.01 mg/L (see
58 of 86
Commented [DF30]: The measured BCF has a range which embraces 500. This conclusion is based on the maximum measured BCF
Commented [MS31R30]: Due to the high volatility of the material, AGCCE believe Aquatic Chronic 4 was not appropriate. Also using a mean BCF value, Aquatic Chronic 4 is also not appropriate.
Section 7). There are no chronic aquatic toxicity data for fish or aquatic invertebrates, but the acute EC50 values are higher than 0.1 mg/L. 1H-Perfluorohexane therefore does not meet the screening criterion for being potentially T based on toxicity to aquatic organisms.
1H-Perfluorohexane does not meet the T criterion based on mammalian toxicity as indicated by the self-classifications for human health presented in the EU REACH registration dossier and C&L Inventory (see Section 9.1). The EU REACH registration dossier has the same conclusion.
No information is available on ED potential.
Overall conclusion: 1H-Perfluorohexane screens as potentially P/vP, but it does not screen as potentially B or T.
The EU REACH registration concludes that the substance is not PBT or vPvB.
9.4 Groundwater hazard
Draft persistence, mobility and toxicity (PMT) criteria have been developed by the German Federal Environment Agency as intrinsic hazard criteria to identify substances that are difficult to remove during normal wastewater treatment practices and may be a threat to remote aquatic environments and drinking water sources, including groundwater (Arp and Hale, 2019). The criteria for P and vP are consistent with those in REACH Annex XIII, whereas the mobile criterion is unique to PMT assessments. The T criteria include those in REACH Annex XIII, in addition to considerations for carcinogenicity, effects via lactation, long-term toxicity to the general human population and ED potential.
There is no legal basis for these criteria under the REACH Regulation, but for completeness, a brief evaluation is included here.
Persistence: 1H-Perfluorohexane meets the screening criterion for being potentially P or vP (see section 9.3).
Mobility: The experimental log Koc value of 3.7 (see Section 6.2.1) meets the draft criterion as being mobile (M) (log KOC 4).
Toxicity: 1H-Perfluorohexane does not meet the T criterion based on mammalian toxicity (see Section 9.1). Additional considerations under the PMT criteria for Carc. 2, Muta. 2 and effects via lactation are not fulfilled. The Registrant has not derived an oral long-term derived no-effect level (DNEL) for the general population because they considered that no effects were demonstrated in the available toxicity studies. No information is available on ED potential.
1H-Perfluorohexane does not meet the T criterion based on aquatic toxicity (see Section 9.1).
59 of 86
Overall conclusion: 1H-Perfluorohexane screens as potentially P/vP and M, but not T. 1H-Perfluorohexane is a relatively volatile liquid, and the influence of volatility is not considered under the criteria.
9.5 Greenhouse gas hazard
1H-Perfluorohexane is a volatile liquid, and a significant proportion of emissions are expected to end up in the atmosphere (see Section 6.2.3). Many fluorinated gases have very high global warming potentials (GWPs) relative to other greenhouse gases, so small atmospheric concentrations can have disproportionately large effects on global temperatures (US EPA, 2020f).
The GWP is defined by the Intergovernmental Panel on Climate Change (IPCC, 2014) as "an index measuring the radiative forcing following an emission of a unit mass of a given substance, accumulated over a chosen time horizon, relative to that of the reference substance, carbon dioxide (CO2). The GWP thus represents the combined effect of the differing times these substances remain in the atmosphere and their effectiveness in causing radiative forcing."
In 2010, fluorinated gases covered under the Kyoto Protocol (F-gases) accounted for 2% of total anthropogenic greenhouse gas emissions (IPCC, 2014) and PFCs contribute to this.
Greenhouse gas emissions for PFCs are quantified as CO2-equivalent emissions (in gigatonnes) (GtCO2-eq) using weightings based on the energy absorbed by a gas over 100 years (the 100-year GWP). PFCs that are close structural analogues of 1H-perfluorohexane are listed in Error! Reference source not found., along with values sourced from IPCC (2013).
Table 9.1 Global warming potential of PFCs
Perfluoroalkane
Trade name
Atmospheric
lifetime (years)
Perfluoropentane
PFC-41-12
4 100
Perfluorohexane
PFC-51-14
3 100
Perfluoroheptane
PFC-61-16
3 000
GWP (100 years) as CO2 equivalent 8 550 7 910 7 820
1H-Perfluorohexane is not listed in IPCC (2013) as it is not a gas. However, several other HFCs are listed. For example, 1,1,1,2,3,3,3-heptafluoropropane (also called HFC227ea or HFC-227; CAS no. 431-89-0) has an atmospheric lifetime of 38.9 years and its GWP (100 years) is reported to be 3 350 GtCO2-eq (IPCC, 2013).
As indicated in Section 6.1.1, 1H-perfluorohexane has a predicted atmospheric half-life of 31 years. Although its atmospheric lifetime is expected to be significantly shorter than PFCs, it could still make a contribution to global warming based on analogy with HFCs. The Environment Agency recommends that this should be considered as part of any emission controls.
60 of 86
Commented [EL32]: GWP and ODP are available publicly on our website for AC-2000 https://www.agcce.com/pure-solvents/
9.6 Limit values
9.6.1 Predicted No Effect Concentration (PNEC) derivation
A PNEC is an indication of an acceptable environmental concentration based on evidence from toxicity studies. Available hazard data are discussed in Sections 7 and 8. The EU REACH Registrant's PNECs are presented in Error! Not a valid bookmark selfreference.. PNECs have also been derived by the Environment Agency following REACH guidance (ECHA, 2008) and are shown in Table 9.3. Due to the lack of effects observed in the acute ecotoxicity studies, a reliable aquatic PNEC cannot be estimated. ECHA (2008) states that a long-term test (on invertebrates, preferably Daphnia) has to be carried out for substances showing no toxicity in short-term tests if the log KOW > 3 (or BCF > 100) and if the Predicted Environmental Concentration (PEC) local or regional is greater than 1/100th of the water solubility (>0.015 mg/L in this case). This is effectively a screening PNEC and so has been used here to give an indication of whether additional chronic ecotoxicity testing may be required. Due to the lack of a reliable aquatic PNEC, soil and sediment PNEC have not been calculated based on the Equilibrium Partitioning Method (EPM) at this time.
Table 9.2 2020a)
PNECs derived for 1H-perfluorohexane by the EU REACH Registrant (ECHA,
Protection goal
PNEC
Notes
Fresh surface water
0.001 mg/L
Freshwater sediment
0.554 mg/kg sediment dw
Equilibrium partitioning method (EPM)
Sewage treatment micro-organisms 10 mg/L
Marine surface water
0.001 mg/L
Marine sediment
0.055 mg/kg sediment dw EPM
Soil
0.109 mg/kg soil dw
EPM
Secondary poisoning
-
No potential for bioaccumulation
Table 9.3 PNECs derived for 1H-perfluorohexane by the Environment Agency
Protection goal Most sensitive Assessment
PNEC
Justification/
toxicity
factor
remarks
descriptor
Fresh water
surface
0.015 mg/L
A reliable PNEC cannot be estimated based on the currently available ecotoxicity data set. A screening PNEC of 1/100th water solubility is used to indicate whether chronic
61 of 86
Commented [MS33]: AGCCE were not aware of this requirement. Does the EA believe that AGCCE is required to do this study? EA, please highlight the section of the requirements that requests this.
Protection goal
Most sensitive toxicity descriptor
Assessment factor
PNEC
Freshwater
sediment
Sewage
3-h ELR50
100
treatment micro- >1 000 mg/L
organisms
Marine surface water
>10 mg/L 0.0015 mg/L
Marine sediment Soil Secondary poisoning
NOAEL: 1 000 mg/kg bw/day
Conversion factor 20 Assessment factor 300
66.67 mg/kg food
Justification/ remarks
ecotoxicity data are required. Not calculated
No sludge respiration EC10 or NOEC available. In the absence of reliable data, an additional assessment factor of 10 has been applied to the fresh water PNEC. Not calculated Not calculated Rats were >6 weeks old at test initiation and the duration of the test was >28 but <90 days.
9.6.2 Qualitative/semi-quantitative descriptors for other critical hazards
A safe threshold is assumed not to exist for PBT/vPvB substances for policy reasons. Since 1H-perfluorohexane is not currently considered to be a PBT/vPvB substance, this is not considered necessary in this case.
As noted in Section 9.5, the substance may contribute to global warming, which could be considered a qualitative hazard.
62 of 86
10 Exposure assessment
10.1 Environment
10.1.1 Environmental releases
The information in this section is based on the Chemical Safety Report (CSR) submitted by AGC Chemicals Europe, Ltd. to ECHA when the UK was still a member of the EU, supplemented with other information from further dialogue with the company. Most of the available information is confidential, so only a summary is presented here.
1H-Perfluorohexane is used as a solvent in the polymerisation process to produce poly(tetrafluoroethylene-co-ethylene) (ETFE), which is subsequently sold to manufacturers of articles in pellet form. Releases of 1H-perfluorohexane occur to air and waste water during the manufacture of fluoropolymers.
ETFE has a wide variety of uses both in industrial processes (e.g. in the semi-conductor industry, in cable coating, in the automotive industry and architecture). 1H-Perfluorohexane can be present as an impurity in the final consumer or industrial product. Environmental releases may therefore occur to waste water and air during the processing and use of ETFE.
10.1.2 Exposure scenarios and measures for reducing emissions to the environment
10.1.2.1 Polymer manufacture
1H-Perfluorohexane is manufactured in Japan and imported to a single site in the UK (AGC Chemicals Europe, Ltd., Fleetwood Road North, Thornton Cleveleys, Lancashire FY5 4QD). An EU REACH registration exists, but the Environment Agency understands that there is no direct supply to any European companies, so the UK site is the only source considered as part of this evaluation.
1H-Perfluorohexane is used exclusively at this site as a solvent in the polymerisation process to make fluorinated copolymer resins. This process involves two production lines. 1H-Perfluorohexane is received in 1 tonne intermediate bulk containers, and pumped into storage tanks and then transferred as necessary to the reactors. Sampling for quality control is not undertaken on the site.
The company has an environmental permit (ref: EPR/BU5453IY) under the Environmental Permitting (England and Wales) Regulations 2016. According to the permit, the fluoropolymer production capacity is 6 000 tonnes/year. The permit does not require any monitoring for 1H-perfluorohexane or require any specific control measures.
When the batch reaction in the reactor is complete, the ETFE slurry is dried and the water / 1H-perfluorohexane mixture is driven off in a number of heating steps to recover and distil
63 of 86
Commented [MS34]: Ethylene-tetrafluoroethylene copolymer
Commented [EL35]: ETFE slurry is processed so the water 1H-perfluorohexane mixture is driven off in a number of heating steps to recover and distil the 1H-perfluorohexane for reuse. ETFE resin is dried at the end of this recovery. The remaining water from this heating process is released as waste water.
the 1H-perfluorohexane for reuse. The remaining water from this heating process is released as waste water.
Routes of emission to surface water
The waste water from the recovery processes, along with waste water from other processes on site, drains to the waste effluent pit prior to discharge to the River Wyre without further on-site treatment.
Routes of emission to land
There is no direct emission to land from the site, and since the wastewater is not treated in a municipal sewage treatment plant (STP), it is not present in sewage sludge that can be spread on agricultural land.
Routes of emission to air
There are 2 main release points in the drying and recovery processes. The first one is storage of the water and 1H-perfluorohexane in a semi-open tank. This tank has a cover but is not sealed. The water enters the tank at approximately 90 C. Undissolved 1H--perfluorohexane sinks to the bottom of this tank. Gaseous 1H-perfluorohexane residing in the headspace of this tank is captured using carbon beds and recovered back to recycled solvent tanks as liquid. However, there are still atmospheric emissions from this tank. The second release point is the ETFE waste water tank. Emissions are possible but much less likely from the main site effluent pit as the temperature of this tank is much lower than the preceding tanks.
10.1.2.2 Polymer use
The quantity of 1H-perfluorohexane in the fluoropolymer products supplied to customers is <0.1 tonnes/year, based on the mass balance.
Routes of emission to surface water
From the limited information available, it is possible that there may be some losses to drain following condensation of any volatilised substance during thermal processing.
Routes of emission to land
The Environment Agency assumes that unused or waste ETFE (and articles containing it) may be disposed of to landfill. The migration rate of any residual 1H-perfluorohexane from the ETFE is unknown.
Routes of emission to air
Releases of 1H-perfluorohexane to air are possible from ETFE during thermal processing at downstream user sites. The worst case assumption is that these sites do not have any abatement on their heating processes and therefore all the 1H-perfluorohexane is released
Commented [MS36]: All effluent in the waste effluent pit is treated in an on-site treatment plant - although this is not designed to capture 1H-perfluorohexane.
waste effluent pit solids removal plant clarifiers effluent / landfill.
AGCCE test filter cake for 1H-perfluorohexane before sending off-site for disposal. Commented [MS37]: Solid waste contaminated with 1Hperfluorohexane will be sent to landfill. ETFE waste, waste effluent pit sludge, filter cake.
Spills contained in bunded areas.
Commented [MS38]: This section should be updated with the improved mass balance data. The main emission point is the SLG exhaust and not the from the storage or water or the semi-open tank (PIT - the PIT headspace is extracted to the SLG).
The SLG is an activated carbon gas/vapour abatement scrubber which captures gaseous 1H-perfluorohexane and recovers it back to recycled solvent tanks as liquid
SLG is a permitted emission point.
64 of 86
to the atmosphere. The mass balance undertaken by AGC Chemicals Europe, Ltd. shows a release of <0.1 tonnes/year.
10.1.3 Release assumptions made by the Environment Agency
The CSR does not contain an exposure assessment, because there is no requirement for the company to do so under EU REACH.
AGC Chemicals Europe, Ltd. supplied a range of information to the Environment Agency, including process information, monitoring data and effluent volumes released to the River Wyre. The following exposure scenarios (ES) were modelled based on:
the volume released in 2019 and the associated monitoring data supplied; and changes in environmental temperature and river flows based on climate change
projections ("future scenario").
10.1.3.1 Current scenario
ES 1: Industrial use - polymer manufacture
Volume released: confidential (based on 2019 data as this was the highest value over the last 3 years).
Number of emission days: 330 days/year (CSR). Releases to surface water: The Environment Agency has calculated a theoretical
maximum release of approximately 40 kg/year using 2019 data based on the water solubility of 1H-perfluorohexane and the amount of waste water discharged from the relevant processes. o Effluent flow: The average daily volume of effluent discharged to the River Wyre
was 803 m3/day in 2018 and 893 m3/day in 2019 (company data). The Environment Agency has assumed that the 2019 average daily flow of 893 m3/day is representative of current operations. o River flow: River flows are measured/calculated at an Environment Agency gauging station which lies roughly 16 km upstream of the AGC Chemicals Europe, Ltd. site (St Michael's flow monitoring station at national grid reference SD4633041131). The long-term daily mean flow was 6.67 m3/s, which equates to 576 288 m3/day. The 95th percentile low flow was 0.61 m3/s, which equates to 52 704 m3/day, and this is the figure that is used in this evaluation. This results in an effluent dilution factor of 60. o Marine dilution factor: For sites that discharge direct to the marine environment, a marine dilution factor can be used. The default is 100. Releases to land: As explained in Section 10.1.2.1, there is no release to agricultural land (e.g. via spreading of sewage sludge) from this site. There may be some local deposition from atmospheric releases. Releases to air: The releases to air are 30.9 tonnes/year over a number of release points in the waste water process, based on the mass balance produced by the company.
65 of 86
ES 2: Industrial use - polymer processing
The Environment Agency considers that, as a worst case, all residual 1H-perfluorohexane can be assumed to be completely released during the polymer processing stage to air for all the grades. The Environment Agency has assumed that there is no abatement to remove the 1H-perfluorohexane from these downstream users' sites. The entire tonnage can also be assumed to be released within the UK (which is also a worst case scenario as the products are supplied outside of the UK too). The fraction of main local source is set to the EUSES default of 0.5, in the absence of any additional information to refine this figure. The number of release days is 20 days/year, as defined in the by ECHA R.16 Guidance Document (ECHA, 2016a).
10.1.4 Predicted Environmental Concentrations (PECs)
Based on confidential information PECs were estimated in various types of environmental media using the EUSES model (version 2.0.3) for the various life cycle stages. The tonnage, release rates and physico-chemical properties are input parameters, and the relevant information for polymer manufacture is summarized in Table 10.1 and Table 10.2.
Table 10.1 Substance-specific input parameters for the EUSES model
Parameter
Values assumed by the Environment Agency
Molecular weight
338.04 g/mol
Vapour pressure
15 kPa at 25 C
Water solubility at 20 oC
1.5 mg/L
Octanol-water partition coefficient (log KOW)
4.1
Octanol-carbon partition coefficient (KOC)
3.7
Note: See Sections 2, 5 and 6 for the origins of these values.
Table 10.2 Scenarios used for the polymer manufacture exposure assessment
Parameter
Reasonable worse case
Annual use at site
confidential
Emission days
330 days/year
Daily use at site
confidential
Regional release to surface water
40 kg/year
Regional release to air
30.9 tonnes/year
Percentage of tonnage used at regional scale
100%
Release factor to water
confidential
Receiving surface water flow rate
52 704 m3/day
The PECs calculated by the Environment Agency are presented in Table 10.3 and Table 10.4.
Table 10.3 Local PECs calculated by the Environment Agency
Life cycle stage
Compartment
PEC
Polymer manufacture
Fresh surface water
1.7 x 10-3
Unit mg/L
Commented [MS39]: This is not the MW of AC-2000, should be 320.05 (MW reported is for C6F14).
Model should be updated and data for the following tables corrected if necessary.
66 of 86
Life cycle stage
Compartment
PEC
Unit
Freshwater sediment
0.206
mg/kg ww
Marine surface water
1.02 x 10-3
mg/L
Marine sediment
0.123
mg/kg ww
Air
0.234
mg/m3
Soil
5.81 x 10-5
mg/kg ww
Groundwater*
1.95 x 10-7
mg/L
Polymer processing (dispersion)
Fresh surface water Freshwater sediment
1.26 x 10-6 1.79 x 10-3
mg/L mg/kg ww
Marine surface water
3.57 x 10-7
mg/L
Marine sediment
2.04 x 10-4
mg/kg ww
Air
0.21
mg/m3
Soil
6.54 x 10-5
mg/kg ww
Note: ww - wet weight
Groundwater*
1.67 x 10-7
mg/L
* The porewater concentration for agricultural soil is used to represent groundwater.
Table 10.4 Regional PECs calculated by the Environment Agency
Compartment
PEC
Unit
Fresh surface water
3.89 x 10-7
mg/L
Freshwater sediment
7.54 x 10-5
mg/kg ww
Marine surface water
2.7 x 10-7
mg/L
Marine sediment
4.61 x 10-5
mg/kg ww
Air
0.21
mg/m3
Groundwater*
2.91 x 10-7
mg/L
Note: ww - wet weight
* The porewater concentration for agricultural soil is used to represent groundwater.
10.1.5 Monitoring data
The company does not have any reliable monitoring data for releases of 1H-perfluorohexane to either waste water or the atmosphere, but is undertaking a project to develop an analytical method and monitoring programme.
67 of 86
11 Risk characterisation
The Environment Agency has estimated PECs arising from the use of 1H-perfluorohexane in the manufacture of ETFE and the worst case downstream user scenario for processing of polymers that contain it in residual amounts (see Section 10.1.2). These can be compared to the PNECs derived in Section 9 to calculate deterministic risk characterisation ratios (RCRs). The RCRs derived by the Environment Agency are shown in Table 11.1. An RCR above 1 indicates a potential risk.
Table 11.1 Risk characterisation ratios derived by the Environment Agency
Life cycle stage
Fresh water
Marine water
Secondary poisoning fish
Polymer manufacture
0.125
0.751
8.38 x 10-3
Polymer processing
1.09 x 10-3
1.24 x 10-3
8.11 x 10-6
Regional
2.57 x 10-5
1.8 x 10-4
The releases to atmosphere are significant, at 30.9 tonnes in 2019. Exposure of soil organisms may occur if 1H-perfluorohexane is transferred from the air to land via deposition. An RCR has not been calculated by EUSES for soil organisms due to the lack of a reliable PNEC. 1H-Perfluorohexane has a predicted atmospheric half-life of 31 years and although its atmospheric lifetime is expected to be significantly shorter than PFCs, it could still make a contribution to global warming based on analogy with HFCs.
The modelling indicates RCR below 1 for the fresh water and marine compartments arising from the polymer manufacturing site. There is significant uncertainty about the releases to the River Wyre. The quantity used by the Environment Agency for modelling purposes was estimated based on the water solubility of 1H-perfluorohexane at 20 C. This does not take into account any losses during the heating and distillation stages of the aqueous waste prior to discharge to the main site waste water system. The Environment Agency recommends that AGC Chemicals Europe, Ltd. continues their project to refine the mass balance, with particular emphasis on environmental releases.
The aquatic PNEC used here are screening values based on the solubility of 1Hperfluorohexane as effects were not observed in the acute ecotoxicity studies. The RCR indicate that additional chronic ecotoxicity testing is not required to refine the assessment.
The Registrant has undertaken to develop an analytical method to monitor 1H-perfluorohexane at levels expected in the aqueous effluent and to significantly improve the mass balance to refine the atmospheric emissions. Once this is done, they have committed to implement additional measures to reduce these emissions.
Commented [MS40]: Indeed, this is a high priority project for AGCCE and significant additional effort and resource has been dedicated to this over the past 6 months.
68 of 86
11.1.1 Future climate scenario
The default temperature of the environmental compartments modelled by EUSES is 12 C. The sensitivity of the modelled PECs to potential changes under future climate change scenarios has therefore been considered, to highlight whether controls may be necessary to avoid future risks. An increase of 4 C in annual mean air temperatures is the maximum change considered in climate change projections published by the Met Office (2020). Increasing the environmental compartment temperature to 16 C had no effect on the PEC values. This is because the substance is assumed to be extremely persistent over a range of ambient temperatures and also has a high vapour pressure, so its general environmental behaviour is likely to be unaffected by a change in temperature of 4 C. Climate change is also expected to have an impact on the amount and distribution of rainfall, and consequently the dilution of STP effluent in rivers during prolonged periods of dry weather. The default dilution factor for STP effluent is 10 for generic modelled scenarios, although the Environment Agency (2013) reported that this value is insufficiently protective of a large proportion of surface watercourses in England (a dilution factor of 2 was recommended). As the discharge of effluent from the manufacturing site is tidal it is difficult to predict what changes there will be to the river flow. The current PECs for discharge to the river are very uncertain and therefore it is not possible to model the impact of reduced dilution until more reliable information has been gathered.
69 of 86
12 Conclusions and recommendations
12.1 Conclusion
1H-Perfluorohexane is a PFAS that belongs to the group of hydrofluorocarbons. It is imported to the UK and used as a non-reactive processing aid at a single site. A large level of release occurs to air during the manufacture of fluoropolymers at this site, and there is also likely to be release of smaller quantities to the River Wyre. Small releases may also occur at polymer processing sites.
Based on the available hazard data the following conclusions can be reached:
1H-Perfluorohexane meets the criteria to be classified as Aquatic Chronic 4 for aquatic environmental hazard under the CLP Regulation.
1H-Perfluorohexane is not readily biodegradable, and is not expected to degrade abiotically. 1H-Perfluorohexane therefore screens as potentially persistent or very persistent.
An experimental bioconcentration study and the log KOW and log KOA indicate that bioconcentration in fish and bioaccumulation in air-breathing organisms are unlikely to be high.
1H-Perfluorohexane does not meet the toxicity criterion of REACH Annex XIII. In summary, 1H-perfluorohexane screens as potentially P/vP, but is unlikely to be B or
T. 1H-Perfluorohexane does not meet the draft PMT criteria. 1H-Perfluorohexane is volatile and is expected to partition significantly to the
atmosphere. It has a long atmospheric half-life and has the potential to be transported to remote regions. It is also likely to be a source of perfluorohexan-1-ol (and potentially other transformation products) for a very long time. Transformation products are likely to be more water soluble than the parent substance, and could therefore be removed from the atmosphere by wet deposition in precipitation and/or more mobile in water. The hazards and risks of these substances need further consideration.
The exposure assessment produced by the Environment Agency has identified RCRs below 1 for fresh and marine surface waters based on a screening PNEC. However, 1Hperfluorohexane has an atmospheric half-life of 31 years and although its atmospheric lifetime is expected to be significantly shorter than PFCs, it could still make a contribution to global warming based on analogy with HFCs.
12.2 Recommendations
Although this evaluation is not a formal assessment under UK REACH, the Environment Agency proposes several recommendations to improve the data package to allow a more robust assessment of the hazards and risks posed by 1H-perfluorohexane. The Environment Agency recommends that the REACH registration dossier is updated with:
70 of 86
a further consideration of the pH variability and potential for colloid formation on the water solubility;
the details of the experimental OECD TG 111 hydrolysis study; additional predicted aquatic ecotoxicity values, to support the conclusions for these
endpoints; a self-classification of Aquatic Chronic 4 for aquatic environmental hazard under the
CLP Regulation; an evaluation of the properties of possible transformation products as part of the risk
assessment.
AGC Chemicals Europe, Ltd. has undertaken to develop an analytical method to monitor 1H-perfluorohexane at levels expected in the aqueous effluent and to significantly improve the mass balance to identify the atmospheric emissions. Once this is done, the exposure assessment could be updated, and if necessary further refined to demonstrate that the RCR is below 1 for all relevant compartments.
1H-Perfluorohexane has an atmospheric half-life of 31 years. Although its atmospheric lifetime is expected to be significantly shorter than PFCs, it could still make a contribution to global warming based on analogy with HFCs. The Environment Agency recommends that this should be considered as part of any emission controls.
The Environment Agency is currently conducting a Regulatory Management Options Analysis (RMOA) for PFAS, and the information summarised in this evaluation will feed into that analysis to identify the most appropriate risk management measures for PFAS in a UK context.
Commented [MS41]: What is the benefit of this? pH dependence not found/expected. More interesting/relevant would be solubility in the presence of MeOH, iso-dodecane.
Commented [MS42]: Disagree, due to the high volatility of 1H-perfluorohexane.
71 of 86
13 References
Arp, H.P. and Hale, S.E., 2019. REACH: Improvement of guidance and methods for the identification and assessment of PMT/vPvM substances. Wrlitzer: Umweltbundesamt.
Chen, L., Tokuhashi, K., Kutsuna, S. and Sekiya, A., 2004. Rate constants for the gas-phase reaction of CF3CF2CF2CF2CF2CHF2 with OH radicals at 250-430 K. Int. J. Chem. Kinet.,
36: 26-33. https://doi.org/10.1002/kin.10170
Chernysheva, V.S. and Skliar, M., 2014. Surface tension of water in the presence of perfluorocarbon vapours. Soft Matter, 10, 1937-1943.
EC, 2000. Guidance for generating and reporting methods of analysis in support of preregistration data requirements for Annex II (part A, Section 4) and Annex III (part A, section 5) of directive 91/414; SANCO/3029/99 rev. 4, 11/07/2000.
ECHA, 2008. Guidance on information requirements and chemical safety assessment:
Chapter R.10: Characterisation of dose [concentration]-response for environment [online].
Helsinki:
European
Chemicals
Agency.
Available
from:
https://echa.europa.eu/documents/10162/13632/information_requirements_r10_en.pdf/bb
902be7-a503-4ab7-9036-d866b8ddce69 [Accessed 01/06/2020].
ECHA, 2011. Guidance on Information Requirements and Chemical Safety Assessment.
Chapter R.4: Evaluation of Available Information. Versions 1.1. December 2011. European
Chemicals
Agency,
Helsinki,
Finland.
https://echa.europa.eu/documents/10162/13643/information_requirements_r4_en.pdf/d63
95ad2-1596-4708-ba86-0136686d205e (accessed July, 2020)
ECHA, 2016a. Guidance on Information Requirements and Chemical Safety Assessment.
Chapter R.16: Environmental Exposure Assessment. Versions 3.0. February 2016.
European
Chemicals
Agency,
Helsinki,
Finland.
https://echa.europa.eu/documents/10162/13632/information_requirements_r16_en.pdf
(accessed July, 2020)
ECHA, 2017a. Guidance on Information Requirements and Chemical Safety Assessment.
Chapter R.7a: Endpoint Specific Guidance. Versions 6.0. July 2017. European Chemicals
Agency,
Helsinki,
Finland.
https://www.echa.europa.eu/documents/10162/13632/information_requirements_r7a_en.p
df (accessed July, 2020)
ECHA, 2017b. Guidance on Information Requirements and Chemical Safety Assessment.
Chapter R.7b: Endpoint Specific Guidance. Versions 4.0. June 2017. European Chemicals
Agency,
Helsinki,
Finland.
https://echa.europa.eu/documents/10162/13632/information_requirements_r7b_en.pdf
ECHA, 2017c. Guidance on Information Requirements and Chemical Safety Assessment. Chapter R.7c: Endpoint Specific Guidance. Versions 3.0. June 2017. European Chemicals
72 of 86
Agency,
Helsinki,
Finland.
https://echa.europa.eu/documents/10162/13632/information_requirements_r7c_en.pdf
ECHA, 2017d. Read-Across Assessment Framework (RAAF). European Chemicals
Agency,
Helsinki,
Finland.
https://echa.europa.eu/documents/10162/13628/raaf_en.pdf/614e5d61-891d-4154-8a47-
87efebd1851a
ECHA, 2019. EUSES - European Union System for the Evaluation of Substances. Version 2.2.0. Available at: https://echa.europa.eu/support/dossier-submission-tools/euses.
ECHA, 2020a. European Chemicals Agency, Helsinki, Finland. [ONLINE]. https://echa.europa.eu/registration-dossier/-/registered-dossier/24103 (Accessed July 2020)
ECHA, 2020b. Summary of Classification and Labelling for Trideca1,1,1,2,2,3,3,4,4,5,5,6,6-fluorohexane [online]. Helsinki: European Chemicals Agency. Available from: https://echa.europa.eu/information-on-chemicals/cl-inventory-database//discli/details/13251. [Accessed July 2020].
ECHA, 2020c. European Chemicals Agency, Helsinki, Finland. [ONLINE]. https://echa.europa.eu/registration-dossier/-/registered-dossier/28093 (Accessed July 2020)
ECHA, 2021. Regulatory Management Option Analysis Conclusion Document Per- and polyfluoroalkyl substances, PFAS. European Chemicals Agency, Helsinki, Finland. [online]. Available from: https://echa.europa.eu/rmoa/-/dislist/details/0b0236e184db2d36
Environment Canada, 2012. Ecological Screening Assessment Report. Long-Chain (C9C20) Perfluorocarboxylic Acids, their Salts and their Precursors.
Gomis, M.I., Wang, Z., Scheringer, M. and Cousins, I.T., 2015. A modeling assessment of the physicochemical properties and environmental fate of emerging and novel per- and polyfluoroalkyl substances. Science of the Total Environment 505, 981-991.
IPCC, 2013. Myhre, G., D. Shindell, F.-M. Bron, W. Collins, J. Fuglestvedt, J. Huang, D.
Koch, J.-F. Lamarque, D. Lee, B. Mendoza, T. Nakajima, A. Robock, G. Stephens, T.
Takemura and H. Zhang, 2013: Anthropogenic and Natural Radiative Forcing. In: Climate
Change 2013: The Physical Science Basis. Contribution of Working Group I to the Fifth
Assessment Report of the Intergovernmental Panel on Climate Change [Stocker, T.F., D.
Qin, G.-K. Plattner, M. Tignor, S.K. Allen, J. Boschung, A. Nauels, Y. Xia, V. Bex and P.M.
Midgley (eds.)]. Cambridge University Press, Cambridge, United Kingdom and New York,
NY,
USA.
https://www.ipcc.ch/pdf/assessmentreport/ar5/wg1/WG1AR5_Chapter08_FINAL.pdf
(accessed 07 December 2020)
73 of 86
IPCC, 2014. Climate Change 2014: Synthesis report. Contribution of Working Groups I, II and III to the Fifth Assessment Report of the Intergovernmental Panel on Climate Change [Core writing team, R.K. Pachauri and L.A. Meyer (eds)]. IPCC, Geneva, Switzerland.
Mansouri, K., Grulke, C.M., Richard, A.M., Judson, R.S. and Williams, A.J. 2016. An automated curation procedure for addressing chemical errors and inconsistencies in public datasets used in QSAR modelling. SAR and QSAR in Environmental Research 27(11) 911937.
Mansouri, K. Grulke, C., Judson, R., and Williams, A. 2018. OPERA: A free and open source QSAR tool for predicting physicochemical properties and environmental fate endpoints. Abst. Papers Am. Chem. Soc. p. 255.
OECD, 1981. Test No. 305C: Degree of bioconcentration in fish, Section 3, OECD Publishing Paris.
OECD, 1992. Environment Monograph No. 61. The Rate of Photochemical Transformation of Gaseous Organic Compounds in Air under Tropospheric Conditions. OCDE/GD(92)172. https://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?doclanguage=en&cote =ocde/gd(92)172
OECD, 1995a. Test No. 105: Water Solubility, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris. https://doi.org/10.1787/9789264069589-en (accessed July, 2020)
OECD, 1995b. Test No. 107: Partition Coefficient (n-octanol/water): Shake Flask Method, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https://doi.org/10.1787/9789264069626-en (accessed July, 2020)
OECD, 2004. Test No. 117: Partition Coefficient (n-octanol/water), HPLC Method, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https://doi.org/10.1787/20745753 (accessed July, 2020)
OECD, 2006a. Test No. 104: Vapour Pressure, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https://doi.org/10.1787/20745753
OECD, 2006b. Test No. 123: Partition Coefficient (1-Octanol/Water): Slow-Stirring Method, OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, https://doi.org/10.1787/9789264015845-en (accessed July, 2020)
OECD, 2012. Test No. 305: Bioaccumulation in Fish: Aqueous and Dietary Exposure. OECD Guidelines for the Testing of Chemicals, Section 3, OECD Publishing, Paris https://www.oecd-ilibrary.org/environment/test-no-305-bioaccumulation-in-fish-aqueousand-dietary-exposure_9789264185296-en (accessed July, 2020)
OECD, 2019. Guidance Document on Aquatic Toxicity Testing of Difficult Substances and Mixtures, OECD Series on Testing and Assessment, OECD Publishing, Paris, https://doi.org/10.1787/0ed2f88e-en.
74 of 86
RSC, 2020a. Royal Society of Chemistry. ChemSpider. [ONLINE]. Version 2020.0.18.0. http://www.chemspider.com/Chemical-Structure.61049.html. (Accessed July 2020)
Stiles, V. E. and Cady, G. H. 1952. Physical Properties of Perfluoro-n-hexane and Perfluoro2-methylpentane. Journal of the American Chemical Society, 74, 3771-3773.
Unpublished, 1994a. Kurume Laboratory. Biodegradation Test of C6H by Microorganisms. June 1994. Unpublished. Cited in ECHA, 2020a.
Unpublished, 1994b. Kurume Laboratory. Bioaccumulation Test of C6H in Carp (study report). March 1994. Unpublished. Cited in ECHA, 2020a.
Unpublished, 1994c. Unpublished. Cited in ECHA, 2020a.
Unpublished, 1994d. Unpublished. Cited in ECHA, 2020a.
Unpublished, 1994e. Unpublished. Cited in ECHA, 2020a.
Unpublished, 2016. Unpublished. Cited in ECHA, 2020a.
Unpublished, 2017a. Determination of the Physicochemical Properties of AsahiklinTM AC2000. Unpublished. Cited in ECHA, 2020a.
Unpublished, 2017b. Charles River Laboratories. Acute Toxicity Study in Daphnia Magna with Asahiklin TM AC-2000 (Static). April 2017. Unpublished. Cited in ECHA, 2020.
Unpublished, 2017c. Charles River Laboratories. Fresh Water Algal Growth Inhibition Test with Asahiklin TM AC-2000. April 2017. Unpublished. Cited in ECHA, 2020.
Unpublished, 2017d. Charles River Laboratories. Activated Sludge Respiration Inhibition Test (Carbon and Ammonium Oxidation) with Asahiklin TM AC-2000. March 2017. Unpublished. Cited in ECHA, 2020.
Unpublished, 2017e. Charles River Laboratories Den Bosch BV. Unpublished. Cited in ECHA, 2020.
Unpublished, 2017f. Unpublished. Cited in ECHA, 2020.
Unpublished, 2020. Covance. ASAHIKLIN AC-2000: Determination of Hydrolysis as a Function of pH. October 2020. Unpublished.
US EPA, 2012. EPISuite v4.11. United States Environmental Protection Agency Office of Pollution Prevention Toxics and Syracuse Research Corporation.
US EPA, 2016. User's Guide for T.E.S.T. (Toxicity Estimation Software Tool), EPA/600/R-
16/058, United States Environmental Protection Agency, Washington, DC, USA [online].
Available
from:
https://www.epa.gov/sites/production/files/2016-
05/documents/600r16058.pdf [Accessed July 2020].
75 of 86
US EPA, 2020. Assessing and Managing Chemicals Under TSCA. Low-priority Substances Under TSCA [online]. United States Environmental Protection Agency, Washington DC, USA. Available from: https://www.epa.gov/assessing-and-managing-chemicals-undertsca/low-priority-substances-under-tsca [Accessed July 2020] US EPA, 2020a. U.S. Environmental Protection Agency. CompTox Chemicals Dashboard. [ONLINE]. https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID20188995 (accessed July 2020) US EPA, 2020b. U.S. Environmental Protection Agency. CompTox Chemicals Dashboard. [ONLINE]. https://comptox.epa.gov/dashboard/DTXSID4042048 (accessed July 27, 2021). US EPA, 2020c. U.S. Environmental Protection Agency. CompTox Chemicals Dashboard. [ONLINE]. https://comptox.epa.gov/dashboard/DTXSID2026949 (accessed July 27, 2021). US EPA, 2020d. U.S. Environmental Protection Agency. Product Properties Test Guidelines: OPPTS 830.7840 Water Solubility: Column Elution Method; Shake Flask Method [EPA 712-C-98-041], March 1998 US EPA, 2020e. U.S. Environmental Protection Agency. Product Properties Test Guidelines: OPPTS 830.7550 Partition Coefficient (n-Octanol/Water), Shake Flask Method [EPA 712-C-96-038], August 1996 US EPA, 2020f. Greenhouse Gas Emissions [ONLINE] U.S. Environmental Protection Agency, Washington, DC. https://www.epa.gov/ghgemissions/overview-greenhousegases#f-gases (Accessed December 2020).
US EPA, 2021. PFAS Analytical Methods Development and Sampling Research. https://www.epa.gov/water-research/pfas-analytical-methods-development-and-samplingresearch (Accessed September 2021). Wegmann, Cavin, MacLeod, Scheringer and Hungerbhler, 2009. The OECD software tool for screening chemicals for persistence and long-range transport potential. Environmental Modeling and Software, 24, 228-237 Williams, A.J., Grulke, C.M., Edwards, J. 2017. The CompTox Chemistry Dashboard: a community data resource for environmental chemistry. J Cheminform 9, 61. https://doi.org/10.1186/s13321-017-0247-6 (accessed July, 2020)
76 of 86
14 List of abbreviations
%
Percentage
B
Bioaccumulative
BAF
Bioaccumulation factor
BCF
Bioconcentration factor
BMF
Biomagnification factor
CAS
Chemical Abstracts Service
CLP
Classification, labelling and packaging (of substances and
mixtures)
cm
Centimetre
CoRAP
Community Rolling Action Plan
CSR
Chemical Safety Report
d
Day
DegT50
Degradation half-life or transformation half-life (days)
DMEL
Derived Minimal Effect Level
DNEL
Derived No Effect Level
DSD
Dangerous Substances Directive
DT50
Dissipation half-life (days)
dw
Dry weight
EC10
10% effect concentration
EC50
50% effect concentration
ELR50
50% effect loading rate
ECETOC TRA
European Centre for Ecotoxicology and Toxicology of Chemicals Targeted Risk Assessment
ECHA
European Chemicals Agency
EPA
Environmental Protection Agency
EPM
Equilibrium Partitioning Method
77 of 86
EQS ERC ES EU EUSES FSDT g GC GC/FID GC/MS GLP H HLC hPa HPLC HSE ISO IUCLID IUPAC kg kJ km KAW KOA KOC KOW
Environmental Quality Standard Environmental release category Exposure Scenario European Union European Union System for the Evaluation of Substances Fish Sexual Development Test Gramme Gas chromatography Gas chromatography - Flame Ionisation Detection Gas chromatography - mass spectrometry Good laboratory practice Hours Henry's Law Constant Hectopascal High performance liquid chromatography Health and Safety Executive International Organisation for Standardisation International Uniform Chemical Information Database International Union of Pure and Applied Chemistry Kilogram Kilojoule Kilometre Air-water partition coefficient Octanol-air partition coefficient Organic carbon-water partition coefficient Octanol-water partition coefficient
78 of 86
kPa KSUSP-WATER kX L LC50 LEV LOD Log LOQ M m/z mg min mL mol MS nm NOAEL NOEC NOEL NONS OC OECD OSPAR
NICNAS
Kilopascal Suspended matter-water partitioning coefficient Rate constants (days-1) Litre 50% lethal effect concentration Local Exhaust Ventilation Limit of detection Logarithmic value Limit of quantitation Molar Mass to charge ratio Milligram Minute Millilitre Mole Mass spectrometry Nanometre No observed adverse effect level No-observed effect concentration No observed effect level Notification of New Substances Regulations 1993 Operational condition Organisation for Economic Co-operation and Development Oslo and Paris Convention for the Protection of the Marine Environment of the North-East Atlantic National Industrial Chemicals Notification and Assessment Scheme
79 of 86
p Pa PACT PBT PC PEC pg PFAS PFOS PFOA pKa PNEC POP ppb PPE ppm PROC QSAR OPERA r2 RCR REACH
RMM RPE rpm SMILES
Statistical probability Pascal Public Activities Co-ordination Tool Persistent, Bioaccumulative and Toxic Product category Predicted environmental concentration Picogramme Per- and polyfluorinated alkyl substances Perfluorooctanesulfonate Perfluorooctanoic acid Acid dissociation constant Predicted no effect concentration Persistent organic pollutant Parts per billion Personal Protective Equipment Parts per million Process Category Quantitative structure-activity relationship OPEn structure-activity/property Relationship App Correlation coefficient Risk characterisation ratio Registration, Evaluation, Authorisation and Restriction of Chemicals (EU Regulation No. 1907/2006) Risk Management Measures Respiratory protective equipment Revolutions per minute Simplified Molecular Input Line Entry System
80 of 86
SVHC t T.E.S.T TG TMF TSCA UNEP UK US EPA UV vB vP VP vPvB WAF WSF wt ww WWTP g
Substance of Very High Concern Tonne Toxicity Estimation Software Tool Test Guideline Trophic Magnification Factor Toxic Substances Control Act United Nations Environment Programme United Kingdom United Stated Environmental Protection Agency Ultraviolet Very bioaccumulative Very persistent Vapour pressure Very persistent and very bioaccumulative Water Accommodated Fraction Water Soluble Fraction Weight Wet weight Wastewater Treatment Plant Microgram
81 of 86
Appendix A: Literature search
A literature search was undertaken by the Environment Agency on the 20th April 2020 to identify published information relevant to the assessment of 1H-perfluorohexane. The keywords listed in Table A.1 were searched for in PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Science Direct (https://www.sciencedirect.com/). In order to maximise the number of records identified keywords were based on the substance name only, and not on the endpoints of interest or year of publication.
Table A. 1 Literature search terms and number of hits
Search terms
PubMed
Science Direct
355-37-3
0
4
Trideca-
0
0
1,1,1,2,2,3,3,4,4,5,5,6,6-
fluorohexane
1H-Perfluorohexane
3
3
1H-Tridecafluorohexane
0
1
Tridecafluorohexane
0
22
Total unique records
3
28
The identified records were screened manually for relevance to this assessment based on the title and abstract. Articles identified as of potential interest were obtained and reviewed for relevance. Those that were found to be relevant are discussed in the appropriate sections of this report.
82 of 86
Appendix B: QSAR models
Two main databases were used to source in silico data for this evaluation when required. These were the United States Environmental Protection Agency (US EPA) CompTox Dashboard (US EPA, 2020a) and the Royal Society of Chemistry (RSC) ChemSpider portal (RSC, 2020a). Both integrate diverse types of relevant domain data through a cheminformatics platform, and are built upon a database of curated substance properties linked to chemical structures (Williams et al., 2017).
The QSAR models available from these two platforms are presented in Table b.1 (data from other open access models are available in the CompTox dashboard, but for the sake of brevity, these have not been used for the purposes of this evaluation).
Table B.1 QSAR model outline
Name
Brief description
ACD/Labs
Predicts physicochemical properties via the Percepta Platform1.
EPISuiteTM
Estimation Programs Interface SuiteTM for Microsoft Windows
A Windows-based suite of physical/chemical, environmental fate and
ecotoxicity property estimation programs developed by the US EPA and
Syracuse Research Corp. It uses a single input (typically a SMILES string) to run the following estimation programs: AOPWINTM, AEROWINTM, BCFBAFTM, BioHCwin, BIOWINTM, ECOSARTM, HENRYWINTM, HYDROWINTM, KOAWINTM, KOCWINTM, KOWWINTM, LEV3EPITM, MPBPWINTM, STPWINTM, WATERNTTM, WSKOWWINTM and WVOLWINTM.
OPEn structure- activity/property Relationship App (OPERA)
Open source suite of QSAR models providing predictions and additional
information including applicability domain and accuracy assessment, as described in Williams et al. (2017). All models were built on curated data and standardized chemical structures as described in Williams et al.
(2016). All OPERA properties are predicted under ambient conditions of
760 mmHg (103 kPa) at 25 C.
T.E.S.T. Toxicity Estimation Software Tool
US EPA software application for estimating the toxicity of chemicals using QSAR methods. EPISuiteTM is the model used to generate some physicochemical data, although T.E.S.T. does not report KOW values and uses a different database for surface tension. (US EPA, 2016).
1 http://www.acdlabs.com/products/percepta/
83 of 86
EPISuiteTM
Table B.2 summarises the PFCs identified in the training/validation sets for EPISuiteTM. Applicability domain (US EPA, 2020c).
Table B.2 EPISuiteTM PFCs included in training and validation sets
EPISuite model
MPBPVP v 1.42
WSKOWWIN v 1.41 Water solubility estimate from fragments (WATERNT v 1.01 est) KOAWIN v 1.1 KOCWIN v 1.66 KOWWIN v 1.67 HENRYWIN v 3.1
Training set
Validation set
tetrafluoromethane
hexafluoroethane
tetrafluoroethylene
octafluoropropane
hexafluoropropene
decafluorobutane
not available
perfluorocyclobutane
perfluoro-n-hexane
perfluorocyclohexane
perfluoroheptane
perfluoromethylcyclohexane
none identified
octafluoropropane octafluorocyclobutane
tetrafluoromethane
hexafluoroethane
trifluoromethane
octafluoropropane
perfluorocyclobutane
tetrafluoroethylene
Uses KOWWIN and HENRYWIN databases
none identified
none identified
tetrafluoromethane hexafluoroethane
perfluorocyclohexane
tetrafluoromethane hexafluoroethane tetrafluoroethene
octafluoropropane perfluorocyclobutane
Open Structure-activity/property Relationship App (OPERA)
OPERA is a free and open-source/open-data suite of QSAR models providing predictions for physicochemical properties, environmental fate parameters, and toxicity endpoints.
Applicability domain (AD) (Williams et al., 2017):
If a chemical is considered outside the global AD and has a low local AD index (< 0.4), the prediction can be unreliable.
If a chemical is considered outside the global AD but the local AD index is average (0.4- 0.6), the query chemical is on the boundary of the training set but has quite similar neighbours (average reliability). If the local AD index is high (> 0.6), the prediction can be trusted.
If a chemical is considered inside the global AD but the local AD index is average (0.4- 0.6), the query chemical falls in a "gap" of the chemical space of the model but still falls
84 of 86
within the boundaries of the training set and is surrounded with training chemicals. The prediction therefore should be considered with caution. If a chemical is considered inside the global AD and has a high local AD index (> 0.6), the prediction can be considered reliable. T.E.S.T. (Toxicity Estimation Software Tool) Data sets used in T.E.S.T. (US EPA, 2016) for parameters reported at 25 C: Surface tension: Dataset for 1 416 chemicals obtained from the data compilation of
Jasper 1972; Water solubility: Dataset of 5 020 chemicals was compiled from the database in EPI
SuiteTM. Chemicals with water solubilities exceeding 1,000,000 mg/L were omitted from the overall dataset; Vapour pressure: Dataset of 2 511 chemicals was compiled from the database in EPI SuiteTM. T.E.S.T. displays structures for substances from the test and training sets that are closest to the substance where a predicted value is required. A comparison between the experimental and predicted value for the substances in the test and training sets provides a similarity coefficient. If the predicted values match the experimental values for similar chemicals in the test and training set (and the similar chemicals were predicted well), there is greater confidence in the predicted value for the substance under evaluation
85 of 86
Would you like to find out more about us or your environment?
Then call us on
03708 506 506 (Monday to Friday, 8am to 6pm)
Email:
genvironment-aciency.ciov.uk
Or visit our website
www.gov.uk/environment-agency
incident hotline
0800 807060 (24 hours)
floodline
0345 988 1188 (24 hours)
Find out about call charges (https://www.ciov.uk/call-charges)
Environment first
Are you viewing this onscreen? Please consider the environment and only print if absolutely necessary. If you are reading a paper copy, please don't forget to reuse and recycle.
86 of 86