Document 3Q8O4nemG6LqyODa5aa4R2yBx

Presented at IAQ *96; Nagoya, Japan; July 18,1996 BASELINE INFORMATION ON INDOOR AIR QUALITY IN LARGE BUILDINGS (BASE `95) *(H H.S. Brightman,1 S.E. Womble,2 E.L. Ronca,2 and J.R. Girman,2 1 Harvard School of Public Health, Boston, MA, USA 2 U.S. Environmental Protection Agency, Office of Radiation and Indoor Air, Washington, DC, USA ABSTRACT A significant data gap exists regarding baseline indoor air quality (IAQ) in public and commercial office buildings in the USA. The U.S. Environmental Protection Agency's (EPA) Office of Radiation and Indoor Air is conducting a major study, entitled the Building Assessment Survey and Evaluation (BASE) Program, to address this gap with the goal of defining the status of the existing building stock. This cross-sectional study has collected baseline data to characterize public and commercial office buildings with respect to key determinants of IAQ and occupant perceptions. For the study, buildings were randomly selected without regard to IAQ complaints. The 'core parameters and methodology specified in an EPA standardized protocol were used to make measurements in a representative space in each building. This paper presents a summary of building descriptions and the results of environmental pollutant measurements and occupant perceptions of IAQ in 16 buildings studied during 1995. The building descriptions include information about building age; location; number of floors; floor area; heating, air-conditioning and ventilation system type; occupancy; and smoking policy. Environmental measurements include concentrations of the sum of targeted volatile organic compounds including formaldehyde, PM|0, fungi and bacteria. Occupant perceptions from a self-administered questionnaire were used to calculate a six-symptom Building Symptom Index (BSI), which is reported as well as the prevalence of selected individual symptoms. The data collected have been coded for confidentiality and are in a soonto-be publicly-accessible data base. INTRODUCTION The Building Assessment Survey and Evaluation (BASE) Program is an on-going, crosssectional study which is designed to address a significant data gap by collecting baseline data to characterize public and commercial office buildings in the USA with respect to key characteristics of IAQ and occupant perceptions. Data from 29 randomly selected buildings currently reside in a soon-to-be publicly available database. The study design, random selection process for buildings and study areas, and selected data from 13 buildings studied during 1994 are contained in two papers presented at the Healthy Buildings `95 Conference.1,2 This paper presents selected data from 16 buildings studied during 1995. It provides a summary of building descriptions including information about building age; size; heating, air-conditioning and ventilation (HVAC) system type; occupant number; and smoking policy. This paper also Disclaimer: Any opinions expressed in this paper are those of the authors and do not necessarily reflect those of Harvard University or the U.S. Environmental Protection Agency nor is any official endorsement to be implied. 794961 0001 summarizes environmental pollutant measurements, and occupant perceptions of IAQ in the 16 buildings, including the sum concentration of volatile organic chemicals (VOCs), formaldehyde,PMt0), and bioaerosols (fungi and bacteria). Other parameters such as temperature, relative humidity, PM2.s, radon, carbon monoxide, and visible fungal growth, were measured in this study but will not be reported in this paper due to limitations of time and space. Occupant perceptions as measured by a self-administered questionnaire were used to calculate a six-symptom Building Symptom Index (BS1), which is reported, as well as the prevalence of selected individual symptoms. MEASUREMENT METHODS A test space was randomly selected within each building with a target population of no less than 50 occupants served by no more than two air handling units. Samplers for VOCs, formaldehyde, PM10, bacteria and fungi were co-located at each of the three indoor and one outdoor sampling sites. Duplicate samples were taken at one indoor and the outdoor site. VOC samples were collected in Summa canisters and analyzed by GC/MS. Formaldehyde samples were collected on DNPH cartridges and analyzed by HPLC. PM,0 samples were collected on filters and analyzed gravimetrically with a microbalance. Bacteria and fungi were collected on six-stage Anderson samplers for two- and five-minute intervals and were cultured on TSA and MEA media respectively. The bacteria Samples were cultured at 30C and 55C. Details on the collection and analysis of these parameters can be found in "A Standardized EPA Protocol for Characterizing Indoor Air Quality in Large Office Buildings."3 QA/QC procedures as described in "The United States Environmental Protection Agency's Large Building Studies Quality Assurance Overview Document"4 were followed. The questionnaire requests information about occupants' symptoms, their perceptions of their buildings' IAQ and work environment, and about other stressors, both at home and at work. The questionnaire was self-administered by occupants of the sampled space on Thursday of the sampling week, with steps taken to maintain confidentiality. The occupants were asked to return the questionnaires by that afternoon, which allowed for any follow-up collection on Friday. RESULTS The database of information which now includes the 13 buildings from BASE `94 and the 16 buildings from BASE `95 is a major step in the study of relationships among building and HVAC features, pollutant concentrations and occupant perceptions, as well as toward establishing a baseline of IAQ information in office buildings nationwide. This paper provides a summary of selected information from BASE `95. Further analyses and hypothesis testing will be possible as the study progresses and more buildings are included. Data summaries are presented in Tables 1 through 4. Buildings are identified with a unique code which identifies the State (with the first two letters), the climatic region by the third letter, and the season (winter (W) or summer (S)), with the fourth letter. The last two digits are a building designation for the study. Table 1 provides summary information regarding the building characteristics. Table 2 contains the results of bioaerosol and PM10 measurements. Bioaerosols, including both fungi and bacteria, were sampled in both the morning and the afternoon. While both mesophyllic (30C) and thermophyllic (55C) bacteria were cultured, only the results for mesophyllic bacteria and fungi collected in the afternoon are reported in Table 2. Indoor PM10 concentrations ranged from 5.3 ug/m3 to 28.6 ug/m3. As was seen in the results from BASE '94 the particulate concentrations were generally -lower indoors than outdoors. The difference 794961 0002 between indoor and outdoor concentrations is more pronounced when outdoor concentration are elevated, buildings seem to attenuate the outdoor concentrations. The variation across sites within a building was low. TABLE 1: Building Characteristics. Data regarding building age, size, study area location, smoking policy, and ventilation type, are shown for the 16 BASE *95 buildings. Building Date Built/ Building Gross No. of Floor(s) No. of Smoking Ventilation ID1 Renovated Envelope Area Floors of Study Occu- policy Type (mJ) Area pants LAGW04 1980 Stone 70,232 27 20 1500 NSC4 VAV/CV* LAGW05 1959 LAGW06 1979 SCDWOI 1900/1985 Glass/ Masonry Glass/ Aluminum Masonry 26,128 74,815 36,752 14 <3 4 5 680 NS5 cv 22 (1700) NSC/S4 1 600 NS/SL5 VAV SCDW02 1965/1970 Masonry 20,686 4 3 900 NS VAV NVAW02 1986 NVAW01 1974 NVAW03 1870/1963 Masonry/ Glass Concrete/ Glass Masonry 31,122 8,191 44,892 6 6 5 2 792 NS 2 259 NS 1 200 NS VAV VAV CV CAEW09 1963 CAEW07 1962 Glass/ Concrete Concrete 6,775 4,134 2 4 1,2` 2,3 197 NS 95 NS/NE7 VAV CV AZHS04 1980 Masonry 1,950 1 l6 165 NS VAV AZHS02 1983/1993 Stucco 17,820 7 1 800 NS VAV FLGS04 1967 Concrete 8,243 7 4,5 200 NS CV FLGS01 PABS04 PABS03 1982 1972 1963 Masonry Concrete/ Glass Concrete 4,538 23,225 6,375 3 3 6 1,2 1 2,3 120 NS 490 NS 350 NS VAV VAV VAV `The buildings are identified with a unique code as follows: the first two letters represent the State abbreviation (e.g., LA represents Louisiana); the third letter represents the climatic region for the BASE study; the fourth letter designates a building studied in winter (W) or summer (S); and the two digits are a building designation for the study. 2 Non-smoking common areas 5 Non-smoking 4 Smoking 5 Smoking lounge, or designated smoking area `Study area included the entire building 7 Non -smoking building but policy not enforced 'Variable Air Volume (VAV)/Constant Volume(CV) In genera], both indoor VOC and formaldehyde concentrations tended to be approximately equal or higher than the outdoor concentrations. In addition, both the indoor and outdoor formaldehyde concentrations tended to be relatively low for this set of buildings, suggesting that formaldehyde sources were not strong. The high sum VOC value for one Nevada building was due overwhelmingly to high dichlorodifluoromethane concentrations. Table 4 presents the results of the self-administered occupant questionnaire. Building occupants were asked to report 794961 0003 juic M;-r Presented at IAQ '96; Nagoya, Japan; July 18,1996 ' (Xrr&^7 BASELINE INFORMATION ON INDOOR AIR QUALITY IN LARGE BUILDINGS (BASE `95) $ H.S. Brightman,1 S.E. Womble,2 E.L. Ronca,2and J.R. Girman,2 1 Harvard School of Public Health, Boston, MA, USA iL&tiU 2 U.S. Environmental Protection Agency, Office of Radiation and Indoor Air, Washington, DC, USA P L A IN T IF F ' S E X H IB IT AL-1083 ABSTRACT A significant data gap exists regarding baseline indoor air quality (IAQ) in public and commercial office buildings in the USA. The U.S. Environmental Protection Agency's (EPA) Office of Radiation and Indoor Air is conducting a major study, entitled the Building Assessment Survey and Evaluation (BASE) Program, to address this gap with the goal of defining the status of the existing building stock. This cross-sectional study has collected baseline data to characterize public and commercial office buildings with respect to key determinants of IAQ and occupant perceptions. For the study, buildings were randomly selected without regard to IAQ complaints. The 'core parameters and methodology specified in an EPA standardized protocol were used to make measurements in a representative space in each building. This paper presents a summary of building descriptions and the results of environmental pollutant measurements and occupant perceptions of IAQ in 16 buildings studied during 1995. The building descriptions include information about building age; location; .:S number of floors; floor area; heating, air-conditioning and ventilation system type; occupancy; and smoking policy. Environmental measurements include concentrations of the sum of targeted volatile organic compounds including formaldehyde, PM,0, fungi and bacteria. Occupant perceptions from a self-administered questionnaire were used to calculate a six-symptom Building Symptom Index (BSI), which is reported as well as the prevalence of selected individual symptoms. The data collected have been coded for confidentiality and are in a soonto-be publicly-accessible data base. INTRODUCTION The Building Assessment Survey and Evaluation (BASE) Program is an on-going, crosssectional study which is designed to address a significant data gap by collecting baseline data to characterize public and commercial office buildings in the USA with respect to key characteristics of IAQ and occupant perceptions. Data from 29 randomly selected buildings currently reside in a soon-to-be publicly available database. The study design, random selection process for buildings and study areas, and selected data from 13 buildings studied during 1994 are contained in two papers presented at the Healthy Buildings `95 Conference.1,2 This paper presents selected data from 16 buildings studied during 1995. It provides a summary of building descriptions including information about building age; size; heating, air-conditioning and ventilation (HVAC) system type; occupant number; and smoking policy. This paper also Disclaimer: Any opinions expressed in this paper are those of the authors and do not necessarily reflect those of Harvard University or the U.S. Environmental Protection Agency nor is any official endorsement to be implied. 794961 0001 summarizes environmental pollutant measurements, and occupant perceptions of IAQ in the 16 buildings, including the sum concentration of volatile organic chemicals (VOCs), formaldehyde,PM10), and bioaerosols (fungi and bacteria). Other parameters such as temperature, relative humidity, PM2.s, radon, carbon monoxide, and visible fungal growth, were measured in this study but will not be reported in this paper due to limitations of time and space. Occupant perceptions as measured by a self-administered questionnaire were used to calculate a six-symptom Building Symptom Index (BSI), which is reported, as well as the prevalence of selected individual symptoms. MEASUREMENT METHODS A test space was randomly selected within each building with a target population of no less than 50 occupants served by no more than two air handling units. Samplers for VOCs, formaldehyde, PM10, bacteria and fungi were co-located at each of the three indoor and one outdoor sampling sites. Duplicate samples were taken at one indoor and the outdoor site. VOC samples were collected in Summa canisters and analyzed by GC/MS. Formaldehyde samples were collected on DNPH cartridges and analyzed by HPLC. PM10 samples were collected on filters and analyzed gravimetrically with a microbalance. Bacteria and fungi were collected on six-stage Anderson samplers for two- and five-minute intervals and were cultured on TSA and MEA media respectively. The bacteria Samples were cultured at 30C and 55C. Details on the collection and analysis of these parameters can be found in "A Standardized EPA Protocol for Characterizing Indoor Air Quality in Large Office Buildings."3 QA/QC procedures as described in "The United States Environmental Protection Agency's Large Building Studies Quality Assurance Overview Document"4 were followed. The questionnaire requests information about occupants' symptoms, their perceptions of their buildings' IAQ and work environment, and about other stressors, both at home and at work. The questionnaire was self-administered by occupants of the sampled space on Thursday of the sampling week, with steps taken to maintain confidentiality. The occupants were asked to return the questionnaires by that afternoon, which allowed for any follow-up collection on Friday. RESULTS The database of information which now includes the 13 buildings from BASE `94 and the 16 buildings from BASE `95 is a major step in the study of relationships among building and HVAC features, pollutant concentrations and occupant perceptions, as well as toward establishing a baseline of IAQ information in office buildings nationwide. This papier provides a summary of selected information from BASE `95. Further analyses and hypothesis testing will be possible as the study progresses and more buildings are included. Data summaries tire presented in Tables 1 through 4. Buildings are identified with a unique code which identifies the State (with the first two letters), the climatic region by the third letter, and the season (winter (W7) or summer (S)), with the fourth letter. The last two digits are a building designation for the study. Table 1 provides summary information regarding the building characteristics. Table 2 contains the results of bioaerosol and PMI0 measurements. Bioaerosols, including both fungi and bacteria, were sampled in both the morning and the afternoon. While both mesophyllic (30C) and thermophyllic (55C) bacteria were cultured, only the results for mesophyllic bacteria and fungi collected in the afternoon are reported in Table 2. Indoor PM|0 concentrations ranged from 5.3 ug/m3 to 28.6 ug/m3. As was seen in the results from BASE '94 the particulate concentrations were generally -lower indoors than outdoors. The difference 794961 0002 between indoor and outdoor concentrations is more pronounced when outdoor concentratic.. are elevated, buildings seem to attenuate the outdoor concentrations. The variation across sites within a building was low. TABLE 1: Building Characteristics. Data regarding building age, size, study area location, smoking policy, and ventilation type, are shown for the 16 BASE `95 buildings. Building Date Built/ Building Gross No. of Floods) No. of Smoking Ventilation ID* Renovated Envelope Area Floors of Study Occu- policy Type (m2) Area pants LAGW04 1980 Stone 70,232 27 20 1500 NSC1 VAV/CV* LAGW05 1959 LAGW06 1979 SCDWOI 1900/1985 Glass/ Masonry Glass/ Aluminum Masonry 26,128 74,815 36,752 14 4 5 680 NS3 CV 22 (f700) NSC/S4 1 600 NS/SL5 VAV SCDW02 1965/1970 Masonry 20,686 4 3 900 NS VAV NVAW02 1986 NVAW01 1974 NVAW03 1870/1963 Masonry/ Glass Concrete/ Glass Masonry 31,122 8,191 44,892 6 6 5 2 792 NS 2 259 NS 1 200 NS VAV VAV CV CAEW09 1963 CAEW07 1962 Glass/ Concrete Concrete 6,775 4,134 2 4 1,26 2,3 197 NS 95 NS/NE7 VAV CV AZHS04 1980 Masonry 1,950 1 l6 165 NS VAV AZHS02 1983/1993 Stucco 17,820 7 1 800 NS VAV FLGS04 1967 Concrete 8,243 7 4,5 200 NS CV FLGS01 1982 Masonry 4,538 3 1,2 120 NS VAV PABS04 PABS03 1972 1963 Concrete/ Glass Concrete 23,225 6,375 3 6 1 2,3 490 NS 350 NS VAV VAV 'The buildings are identified with a unique code as follows: the first two letters represent the State abbreviation (e.g., LA represents Louisiana); the third letter represents die climatic region for the BASE study; the fourth letter designates a building studied in winter (W) or summer (S); and the two digits are a building designation for the study. 2 Non-smoking common areas 3 Non-smoking 4 Smoking 5 Smoking lounge, or designated smoking area `Study area included the entire building 7 Non -smoking building but policy not enforced 'Variable Air Volume (VAV)/Constant VoIume(CV) In genera], both indoor VOC and formaldehyde concentrations tended to be approximately equal or higher than the outdoor concentrations. In addition, both the indoor and outdoor formaldehyde concentrations tended to be relatively low for this set of buildings, suggesting that formaldehyde sources were not strong. The high sum VOC value for one Nevada building was due overwhelmingly to high dichlorodifluoromethane concentrations. Table 4 presents the results of the self-administered occupant questionnaire. Building occupants were asked to report i 794961 0003 symptoms for the last week and questionnaires was high, 83%. the last month. The occupant response rate for completing Table 2. Fungi, Bacteria, and PMI0. The range for the sum of 36 genus/species of fungi and 7 classifications of bacteria for three indoor sites, two-minute, afternoon samples and the arithmetic mean (AM) and standard deviation (ASD) for duplicates at the outdoor site, afternoon, two minute samples taken for the 16 `95 BASE buildings. PM,0 measurements at each of the indoor sites and the AM and ASD for the outside measurements. PM2j measurements were made at one indoor site and outdoor but are not reported due to space limitations. Building Fungi' - cfii/mJ Bacteria - cfu/mJ PM,0-pg/mJ ID Indoor Outdoor Indoor Outdoor Indoor Outdoor Range AM (ASD) Range AM (ASD) Site 1 Site 2 Site 3 P2 dm LAGW04 35-371 575(112) 18-203 292(37) 13.4 4.7 6.2 15.8 14.7 LAGW05 0-88 300(0) 18-124 362(87) 11.3 _5 12.0 51.4 48.8 LAGW06 159(50) <j8jl2^' 159(25) 6 12.1 6.7 SCDW01 35-194 159(26) 88-194 106(25) 15 2 17.6 11.0 9.1 8.4 SCDW02 ' 0-18 NC7 35-124 NC 10.6 12.0 8.5 18.6 15.6 NVAW02 0-106 NC 71-124 NC 12.4 9.6 12.3 5.8 7.1 NVAW01 0-53 115(38) 132-230 283(175) 12.5 12.9 12.6 51.2 48.0 NVAW03 18-88 115(13) 124-159 168(62) 11.3 16.8 12.3 10.6 12.1 CAEW09 265-530 1281(16?) 230-389 1387(13) 10.7 11.8 6.0 19.9 22.7 CAEW07 0-88 247(0) 106-212 327(237) 6.9 7.1 9.1 13.6 14.1 AZHS04 53-3462 221(38) 71-247 265(150) 6.7 7.4 8.0 31.5 35.3 AZHS02 35-141 168(13) 97-336 141(50) 9.0 12.1 31.1 34.0 33.6 FLGS04 0-177 813(150) 106-813 10257 5.3 7.4 9.3 7.6 8.4 FLGS01 0-106 353(150) 159-177 62(13) 12.6 23.9 28.6 102.8 98.6 PABS04 53-194 1405(112) 27-495 327(187) 16.1 14.3 16.0 38.1 38.1 PABS03 0-53 865(175) tt:------ :-----------1 .------:--"tttt; 133-177 53(0) 15.0 14.8 11.7 25.4 26.4 Primary Sample duplicate Sample Average relative standard deviation for duplicates was 8.5%. PM, j was measured instead of PM ,0 6Sample voided by lab Sample not collected due to very heavy rain. 'Duplicate below detection limit The symptom prevalences reported in Table 4 are unadjusted for gender, job classification or age, although this information was collected for future analysis. The symptoms for each individual were used to calculate a Personal Symptoms Index (PSI) by summing the number of the six symptoms reported by each occupant. Symptoms were counted in the PSI only if that symptom "got better" when the respondent was away from work. These PSI values were then averaged for each building to create a Building Symptom Index (BSI), which can range from 0 to 6. 794961 0004 SUMMARY This data set represents the first step toward obtaining baseline data to characterize public and commercial office buildings in the U.S. with respect to IAQ and occupant perceptions toward it. This is a rich data set which allows examination of possible relationships among building and HV.AC features, pollutant concentrations and occupant symptoms. In addition, the data will provide a sound basis for hypothesis development in subsequent studies. As more buildings are studied (five additional buildings have already been studied during the 1995-6 winter season), data will become more representative of the current status of the U.S. building stock and occupant perceptions. Table 3. VOCs and Formaldehyde. Sum of volatile organic chemicals in ug/m3 measured using the EPA TO-14 standard test method and the concentrations of formaldehyde also in ug/m3. Building VOCs ug/m3 Formaldehyde ug/mJ ID Indoor Outdoor Indoor Outdoor Site 1 Site 2 Site 3 P' D13 Site 1 Site 2 Site 3 P D4 LAGW04 462 424 515 28 32 9 1 BQLk BQL 1 LAGW05 206 178 199 113 112 6 8 7 AQL7 BQL V/? is^LAGW06 C (Oir ( ( kMAu' 14 58 <& 2 1 SCDW01 144 140 313 38 39 7 9 8 AQL AQL SCDW02 101 199 149 32 33 12 15 17 BQL BQL NVAW02 1935s 13585 21085 204 248 9 6 8 1 I NVAW01 69 64 160 47 38 4 4 5 BQL 1 NVAW03 58 70 119 38 26 3 3 4 1 1 CAEW09 63 83 103 35 97 8 9 10 3 1 CAEW07 47 33 53 23 23 5 6 5 4 2 AZHS04 174 159 191 297 24 17 21 21 2 2 AZHS02 69 126 94 49 33 8 12 9 2 3 FLGS04 441 394 440 72 - 45 21 29 27 BQL AQL FLGS01 - 119 146 81 53 9 11 11 8 7 PABS04 260 174 165 29 130 13 13 14 5 4 PABS03 388 371 460 44 57 15 16 15 5 5 Primary Sample duplicate Sample 3The average relative standard deviation for duplicates was 25%. *The average relative standard deviation for duplicates was 20%. 5The reported concentration is mostly due to the contribution of dichlorodifloromethane. ^elow the quantitation limit of 0.4 ug/m3. 7At the quantitation limit. 794961 0005 Table 4. Building Symptom Index (BSI), based on six self-reported symptoms that got better when occupants were away from work. BSI This Month is for the past four weeks preceding the study and BSI This Week is for the week of the study. The questionnaire was administered on Thursday. Also shown are the symptom prevalence for the six symptoms used to calculate the BSI for tire sixteen BASE `95 buildings._____________________________ Building BSI BSI Dry, Itching Head Sore or Unusual Stuffy or Dry or ID This This or Irritated ache Dry Tiredness, Runny Nose, Itchy Month Week Eyes This This Throat Fatigue or or Sinus Skin This Week Week This Drowsiness Congestion Week Week This Week This Week LAGW04 0.89 0.56 0.06 0.27 0.03 0.11 0.08 0.02 LAGW05 2.02 1.52 0.46 0.22 0.11 0.28 0.37 0.07 LAGW06 (OT) (055) Coff (0.^ <TT04^ COUP ("0.04 SCDW01 1.18 0.96 0.18 0.19 0.13 0.18 021 0.07 SCDW02 0.78 0.74 0.26 0.26 0.04 0.13 0.04 0.00 NVAW02 1.49 1.06 0.27 0.31 0.08 024 0.08 0.08 NVAW01 1.23 0.98 0.20 023 0.10 025 020 0.00 NVAW03 2.22 1.67 0.42 0.40 0.16 0.33 0.31 0.04 CAEW09 1.84 1.39 0.39 0.29 0.16 0.30 0.20 0.05 CAEW07 . 0.81 0.47 0.06 0.25 0.03 0.06 0.06 0.00 AZHS04 1.46 1.08 0.22 0.27 0.19 0.19 0.16 0.05 AZHS02 1.22 0.83 0.14 ' 022 0.11 0.19 0.11 0.06 FLGS04 1.44 0.74 0.22 0.16 0.10 0.16 0.06 0.04 FLGS01 1.26 1.02 0.28 0.20 0.08 0.20 0.18 0.08 PABS04 1.98 1.44 0.35 0.31 021 0.27 020 0.08 PABS03 .1.58 1.24 0.29 0.29 0.13 0.31 0.18 0.04 ACKNOWLEDGMENT We would like to acknowledge the efforts and care taken by the staff of Environmental Health & Engineering in conducting the field work and by the staff of ManTech in assuring the quality of the data. REFERENCES 1. Womble, S.E.;Girman, J.R.; Ronca, E.L.; et al. 1995. "Developing Baseline Information on Buildings and Indoor Air Quality (BASE '94): Part I-Study Design, Building Selection, and Building Descriptions." Proceedings ofHealthy Buildings `95, Milan, Italy, Vol. 3, pp. 1305-1310. 2. Girman, J.R.; Womble, S.E.; and Ronca, E.L. 1995. "Developing Baseline Information on Buildings and Indoor Air Quality (BASE'94): Part II - Environmental Pollutant Measurements and Occupant Perceptions." Proceedings ofHealthy Buildings `95, Milan, Italy, Vol. 3, pp. 1311-1316. 3. U.S. Environmental Protection Agency. 1994. "A Standardized EPA Protocol for Characterizing Indoor Air Quality in Large Office Building," Office of Research and Development and Office of Air and Radiation, U.S. Environmental Protection Agency, Washington, DC, USA. 4. U.S. Environmental Protection Agency. 1994. "The United States Environmental Protection Agency's Large Building Studies Quality Assurance Overview Document," Office of Research and Development and Office of Air and Radiation! 794961 0006 Author: John B. Cunningham at -PITCCN4 Date: 7/10/96 5:39 PM Priority: Normal TO: Donald J. Moeslein at -AMPCCN3 Subject: air quality at 2AC ------------------------------------------------------------------------------------- Message Contents -------- Don, How should we test for air quality? John Subject: air quality at 2AC From: Kathleen M. Hovanec at -PITCCN8 Date: 7/10/96 3:25 PM John, I'm still having a problem with the air quality here in 2AC. Persistent headaches and a general feeling of fatigue or sleepiness appear within an hour of arriving at the building, persist while I'm here and then just disappear after I'm out of here for about 20-30 minutes. One thing I did notice is that when I was here after 6PM (when the air circulation is off) on Monday, the headache went away by 6:30. I know I've mentioned this before, but other people here on the 4th floor have experienced the same symptoms which generally disappear after they are out of the building for a short while. This surely presents a health/safety concern, not only from the standpoint of possible errors of judgment occurring, but also the regular consumption of aspirin, Tylenol, etc. and high levels or caffeine in the effort to overcome these symptoms isn't good for anyone's health. In doing some reading, these symptoms have been linked to insufficient levels of oxygen, excessive levels of carbon dioxide or carbon monoxide; airborne pollutants (with all the construction going on in the building, this wouldn't surprise me); and mold/mildew from insufficiently/improperly cleaned air conditioning equipment (this can be particularly bad, as it can cause a severe form of pneumonia generally know as Legionnaire's disease). I think it has been dubbed "sick building syndrome." Could we please have the air quality for these things (you're probably more aware than I am of things they test for) to see just what we are breathing every day? Thanks! 794961 0007 2 and other airborne substances which nay cause material impairment to employees working within the nonindustrial environment. Assistant Secretary means the Assistant Secretary of Labor for Occupational Safety and Health, U.S. Department of Labor, or designee. Building-related illness describes specific medical conditions of known etiology which can be documented by physical signs and laboratory findings. Such illnesses include sensory irritation when caused by known agents, respiratory allergies, asthma, nosocomial infections, humidifier fever, hypersensitivity pneumonitis, Legionnaires' disease, and the signs and symptoms characteristic of exposure to chemical or biologic substances such as carbon monoxide, formaldehyde, pesticides, endotoxins, or mycotoxins. Comment: Support inclusion only of illness documented by physical signs and laboratory findings. Building systems include but are not limited to the heating, ventilation and air-conditioning (HVAC) system, the potable water systems, the energy management system and all other systems in a facility which may impact indoor air quality. Comment: Add "are systems that may have an impact on indoor air quality and" after "Building systems" above. Delete "potable water systems" and substitute "systems that could result in aerosolized microbial contaminants that could cause BRI." Designated person means a person who has been given the responsibility by the employer to take necessary measures to assure compliance with this section and who is knowledgeable in the requirements of this standard and the specific building systems servicing the affected building or office. Designated smoking area means a room, in a non-work area, in which smoking of tobacco products is permitted. Director means the Director, National Institute for Occupational Safety and Health (NIOSH) U.S. Department of Health and Human Services or designee. Employer means all persons defined as employers by Sec. 3(5) of the Occupational Safety and Health Act of 1970 including employers (such as building owners or lessees) who control the ventilation or maintenance of premises where employees of other employers work. 794961 0010 i j=l Organization Resources is] Counselors, inc. 1910 Sunderland Place, N.W. Washington, D.C. 20036 Tel: 202-293-2980 Fax: 202-293-2915 Memorandum May 26, 1994 To: ORC Indoor Air Quality Task Force From: Ann Brockhau Subject: Draft ORC Comments Attached is a very preliminary draft of ORC comments on the OSHA IAQ proposal. I will send a more polished draft within the next two weeks. I look forward to getting your reactions. OSHA has not yet made a decision on extending the comment period. A 60 day extension is likely. I will let you know when a decision is made. If the comment period is not extended, I will need your comments by June 23, 1994. AB/ab 794961 0008 3 HVAC system means the collective components of the heating, ventilation and air-conditioning system including, but not limited to, filters and frames, cooling coil condensate drip pans and drainage piping, outside air dampers and actuators, humidifiers, air distribution ductwork, automatic temperature controls, and cooling towers. Nonindustrial work environment means an indoor or enclosed work space such as, but not limited to, offices, educational facilities, commercial establishments, and healthcare facilities, and office areas, cafeterias, and break rooms located in manufacturing or.production facilities used by employees. Nonindustrial work environments do not include manufacturing and production facilities, residences, vehicles, and agricultural operations. Comment: D.O. to send additional comment. Add "warehouses" to list of exemptions. Renovation and remodeling means building modification involving activities that include but are not limited to: removal or replacement of walls, ceilings, floors, carpet, and components such as moldings, cabinets, doors, and windows; painting, decorating, demolition, surface refinishing, and removal or cleaning of ventilation ducts. (c) Indoor air quality (IAQ) compliance program. (1) All employers with workplaces covered by paragraph (a)(1) of this section shall establish a written IAQ compliance program. '(2) The employer shall identify a designated person who is given the responsibility to assure implementation of the IAQ compliance program. Comment: Support (c)(1) and (2). (3) Written plans for compliance programs shall include at least the following: (i) A written narrative description of the facility building systems; (ii) Single-line schematics or as-built construction documents which locate major building system equipment and the areas that they serve; (iii) Information for the daily operation and management of the building systems, which shall include at least a description of normal operating procedures, special procedures such as seasonal start-ups and shutdowns, and a list of 794961 0011 4 operating performance criteria including, but not limited to minimum outside air ventilation rates, potable hot water storage and delivery temperatures, range of space relative humidities, and any space pressurization requirements; (iv) A general description of the building and its function including but not limited to, work activity, number of employees and visitors, hours of operation, weekend use, tenant requirements and known air contaminants released in the space; Comment: Delete (c)(3)(i)-(iii) and include in a non mandatory appendix "Model Indoor Air Quality Management Plan." (v) A written maintenance program for the maintenance of building systems which shall be preventive in scope and reflect equipment manufacturer's recommendations and recommended-good-practice as determined by the building systems maintenance industry. At a minimum, the maintenance program shall describe the equipment to be maintained, and establish maintenance procedures and frequency of performance; (vi) A checklist for the visual inspection of building systems. Comment: Support (c)(3)(v) and (vi). (4) The following additional information, if available, shall be retained by the employer to assist in potential indoor air quality evaluations: (i) As-built construction documents; (ii) HVAC system commissioning reports; (iii) HVAC systems testing, adjusting and balancing reports; (iv) Operations and maintenance manuals; (v) Water treatment logs; and (vi) Operator training materials. (5) The employer shall establish a written record of employee complaints of signs or symptoms that may be related to building-related illness to include at least information on the nature of the illness reported, number of employees affected, date of employee complaint, and remedial action, if any, taken to correct the source of the problem. 794961 0012 5 Comment: Oppose this requirement. BRI as defined by OSHA is recordable on the OSHA 200 Log. Complaints investigated and readily resolved, and not found to be consistent with BRI, should not have to be recorded. This section could instead require a written procedure for receiving and responding to IAQ complaints. (d) Compliance program implementation. Employers shall assure compliance with this section by implementing at least the following actions: (1) Maintain and operate the HVAC system to assure that it operates up to original design specifications and continues to provide at least the minimum outside air ventilation rate, based on actual occupancy, required by the building code, mechanical code, or ventilation code applicable at the time the facility was constructed, renovated, or remodeled, whichever is most recent; Comment: Change wording to the following: (1) Maintain and operate the HVAC system to assure that it operates up to original design specifications and continues to provide at least the minimum outside air ventilation rate, based on actual occupancy, required by the applicable building code, mechanical code, or ventilation code; (2) Conduct building systems inspections and maintenance in accordance with paragraph (c) of this section; (3) Assure that the HVAC system is operating during all work shifts, except during emergency HVAC repairs and during scheduled HVAC maintenance; Comment: Employers must have the flexibility to adjust the HVAC system appropriately during periods of reduced demand. P.O. to provide additional comment on this. Wording?? (4) Implement the use of general or local exhaust ventilation where housekeeping and maintenance activities involve use of equipment or products that could reasonably be expected to result in hazardous chemical or particulate exposures to employees working in other areas of the building or facility; Comment: Needs clarification. D.E. and J.B. to provide additional comment. It has been suggested that this section and other similar sections [sections (e)(2)(ii), (f)(1), (f)(2), and (f)(3)] be deleted and placed in a non-mandatory appendix. Another approach is as follows: 794961 0013 6 (4) Implement: the use appropriate controls such as local exhaust ventilation where housekeeping and maintenance activities involve use of equipment or products that could reasonably be expected to result in chemical or particulate exposures at levels that could cause BRI to employees working in other areas of the building or facility? (5) Maintain relative humidity below 60% in buildings with mechanical cooling systems; Comment: Delete; not defensible or always feasible. Meed volunteer to write argument for this. (6) The employer shall monitor carbon dioxide levels when routine maintenance under paragraph (d)(1) of this section is done. When the carbon dioxide level exceeds 800 ppm, the employer shall check to make sure the HVAC system is operating as it should. If it is not, the employer shall take necessary steps to correct deficiencies if they exist. Comment: Recommend this be placed in a non-mandatory appendix Model Indoor Air Quality Management Plan." (7) Assure that buildings without mechanical ventilation are maintained so that windows, doors, vents, stacks and other portals designed or used for natural ventilation are in operable condition; (8) Assure that mechanical equipment rooms and any non-ducted air plenums or chases that transport air are maintained in a clean condition, hazardous substances are properly stored to prevent spillage, and asbestos, if friable, is encapsulated or removed so that it does not enter the air distribution system; Comment: Delete reference to asbestos, as this duplicates requirements likely to be soon to be published asbestos rule. New wording: (8) Assure that mechanical equipment rooms and any non--ducted air plenums or chases that transport air are maintained in a clean condition, and hazardous substances are properly stored to prevent spillage. (9) Assure that inspections and maintenance of building systems are performed by or under the supervision of the designated person; (10) Establish a written record of building system inspections and maintenance required to be performed under this section; 794961 0014 7 (11) Assure that employees performing work on building systems are provided with and use appropriate personal protective equipment as prescribed in 29 CFR part 1926, subpart E, Personal Protective and Life Saving Equipment? 29 CFR part 1926.52, Occupational Noise Exposure; 29 CFR part 1910, subpart I, Personal Protective Equipment? and 29 CFR part 1910.95, Occupational Noise Exposure? Comment: Delete; not necessary to refer to other standards. May be provided as information to employers in a non-mandatory appendix "Model Indoor Air Quality Management Plan." (12) Evaluate the need to perform alterations of the building systems to meet the minimum requirements specified in paragraph (d) of this section in response to employee complaints of building-related illnesses; and (13) Take such remedial measures as the evaluation shows to be necessary. (e) Controls for specific contaminant sources. (1) Tobacco smoke. (i) In workplaces where the smoking of tobacco products is not prohibited, the employer shall establish designated smoking areas and permit smoking only in such areas; (ii) The employer shall assure that designated smoking areas are enclosed and exhausted directly to the outside, and are maintained under negative pressure (with respect to surrounding spaces) sufficient to contain tobacco smoke within the designated area; (iii) The employer shall assure that cleaning and maintenance work in designated smoking areas is conducted only when no smoking is taking place; (iv) The employer shall assure that employees are not required to enter designated smoking areas in the performance of normal work activities; (v) The employer shall post signs clearly indicating areas that are designated smoking areas; (vi) The employer shall post signs that will clearly inform anyone entering the workplace that smoking is restricted to designated areas; and (vii) The employer shall prohibit smoking within designated smoking areas during any period that the exhaust ventilation system servicing that area is not properly operating. 794961 0015 8 Comment: Support as written (1)(i)-(vii), consistent with ORC comments in response to the RFI. (2) Other indoor air contaminants. (i) The employer shall implement measures such as the relocation of air intakes and other pathways of building entry, where necessary, to restrict the entry of outdoor air contaminants such as vehicle exhaust fumes, into the building; Comment: F.G. to improve wording. (ii) When general ventilation is inadequate to control air contaminants emitted from point sources within workspaces the employer shall implement other control measures such as local source capture exhaust ventilation or substitution. Comment: Reword to be consistent with (d)(4). Suggest the following wording: "Implement the use of other control measures such as local source capture exhaust ventilation or substitution when necessary to prevent accumulation of air contaminants emitted from point sources within workspaces at levels that could reasonably be expected to result in building related illness." (3) Microbial contamination. (i) The employer shall control microbial contamination in the building by routinely inspecting for, and promptly repairing, water leaks that can promote growth of biologic agents; (ii) The employer shall control microbial contamination in the building by promptly drying, replacing, removing, or cleaning damp or wet materials; and Comment: Improve wording as follows: "The employer shall control microbial contamination in the building by promptly using effective means such as drying, replacing, removing, or cleaning damp or wet materials; and" (iii) The employer shall take measures to remove visible microbial contamination in ductwork, humidifiers, other HVAC and building system components, or on building surfaces when found during regular or emergency maintenance activities or during visual inspection. (4) Use of cleaning and maintenance chemicals, pesticides, and other hazardous chemicals in the workplace. (i) The employer shall assure that these chemicals are used and applied according to manufacturers' recommendations; and 794961 0016 9 (ii) The employer shall inform employees working in areas to be treated with potentially hazardous chemicals, at least within 24 hours prior to application, of the type of chemicals intended to be applied. Comment: Help!!! We considered recommending that this be deleted because we thought HazCom might take care of this, but now I'm not so sure. It may be defensible to leave this in. What do you think? (f) Air quality during renovation and remodeling. (1) General. During renovation or remodeling, the employer shall assure that work procedures and appropriate controls are utilized to minimize degradation of the indoor air quality of employees performing such activities and employees in other areas of the building. Comment: Vague wording about "degradation" needs to be improved. Sections (d)(4), (e)(2)(ii), (f)(1), (f)(2), and (f)(3), should all be consistent. Suggest the following wording: (1) General. During renovation or remodeling, the employer shall assure that work procedures and appropriate controls are utilized where equipment or products are used that could reasonably be expected to result in chemical or particulate exposures at levels that could cause BRI to employees working in other areas of the building or facility; (2) Work plan development. (i) Before remodeling, renovation, or similar activities are begun the employer shall meet with the contractor or individual(s) performing the work and shall develop and implement a work plan designed to minimize entry of air contaminants to other areas of the building during and after performance of the work; and Comment: Change to be consistent with Sections (d)(4), (e)(2)(ii), and (f)(1), as follows: (i) Before remodeling, renovation, or similar activities are begun the employer shall meet with the contractor or individual(s) performing the work and shall develop and implement a work plan designed to assure that work procedures and appropriate controls are utilized where equipment or products are used that could reasonably be expected to result in chemical or particulate exposures at levels that could 794961 0017 10 cause BRI to employees working in other areas of the building or facility; (ii) The work plan shall consider all of the following where appropriate; (A) Requirements of this standard. (B) Implementation of means to assure that HVAC systems continue to function effectively during remodeling and renovation activities. (C) Isolation or containment of work areas and appropriate negative pressure containment. (D) Air contaminant suppression controls or auxiliary air filtration/cleaning. (E) Controls to prevent air contaminant entry into the HVAC air distribution system. Comment: (E) Should be reworded to be consistent with Sections (d)(4), (e)(2)(ii), and (f)(1), and (f)(2) as follows: (E) Other work procedures and appropriate controls as necessary where equipment or products are used that could reasonably be expected to result in chemical or particulate exposures at levels that could cause BRI to employees working in other areas of the building or facility; (3) Prior notification of employees who work in the building. (i) The employer shall notify employees at least 24 hours in advance, or promptly in emergency situations, of work to be performed on the building that may introduce air contaminants into their work area; Comment: Revise wording as follows: (i) The employer shall notify employees at least 24 hours in advance, or promptly in emergency situations, of work to be performed on the building that may result in potentially hazardous exposures in their work area; (ii) Notification shall include anticipated adverse impacts on indoor air quality or workplace conditions. (g) Employee information and training. 794961 0018 11 (1) The employer shall provide training for maintenance workers and workers involved in building system operation and maintenance which shall include at least the following: (1) Training in the use of personal protective equipment (PPE) needed in operating and maintaining building systems; Comment: Delete; covered by PPE standard. (ii) Training on how to maintain adequate ventilation of air contaminants generated during building cleaning and maintenance; and (iii) Training of maintenance personnel on how to minimize adverse effects on indoor air quality during the use and disposal of chemicals and other agents. (2) All employees shall be informed of: (i) The contents of the standard in this section and its appendices; and (ii) Signs and symptoms associated with building-related illness and the requirement under paragraphs (d)(12) and (d)(i3) of this section directing the employer to evaluate the effectiveness of the HVAC system and to take remedial measures to the HVAC system if necessary, upon receipt of complaints from employees of building-related illness. Comment: Delete. Change wording to "Employees should be informed of the employer's procedures for receiving employee indoor air quality concerns." This procedure should be included in the employer's written compliance program. (3) Availability of training material. The employer shall make training materials developed in response to paragraph (g), including the standard in this section and its appendices, available for inspection and copying by employees, designated employee representatives, the Director, and the Assistant Secretary. (h) Recordkeeping. (1) Maintenance records. The employer shall maintain inspection and maintenance records required to be established under paragraph (d) of this section, which shall include the specific remedial or maintenance actions taken, the name and affiliation of the individual performing the work, and the date of the inspection or maintenance activity. 794961 0019 12 (2) Written IAQ compliance program. The employer shall maintain the written compliance program and plan required to be established under paragraph (c) of this section. (3) Employee complaints. The employer shall maintain a record of employee complaints of signs or symptoms that may be associated with building-related illness required to be established under paragraph (c)(5) of this section. These complaints shall be promptly transmitted to the designated person for resolution. Comment: Delete and include in non-mandatory appendix to be consistent with (c)(5). (4) Retention of records. The employer shall retain records required to be maintained under this section for at least the previous three years, except that records required to be maintained under paragraphs (h)(1) and (h)(2) of this section need not be retained for three years if rendered obsolete by the establishment and replacement of more recent records, or rendered irrelevant due to HVAC system replacement or redesign. (5) Availability. The records required to be maintained by this paragraph shall be available on request to employees and their designated representative and the Assistant Secretary for examination and copying. (6) Transfer of records. Whenever the employer ceases to do business, records that are required to be maintained by paragraph (h) of this section shall be provided to and retained by the successor employer. (1) Dates. (1) Effective date. This section is effective [DATE 60 DAYS FROM PUBLICATION OF THE FINAL RULE] (2) Start-up dates. Employers shall have implemented all provisions of this standard no later than one year from [THE EFFECTIVE DATE OF THE FINAL RULE]. 794961 0020 VI. Factors influencing the dose for aerosols a. Factors influencing total dose (total deposition) b. Factors influencing regional deposition i) sedimentation ii) impaction iii) diffusion iv) electrostatic forces v) interception vi) quick summary VII. Retention - Clearance a. Model b. Input c. Absorption - translocation processes d. implication of the model e. Man vs. laboratory animals VIII. Factors influencing the dose for gases, vapors 1. High water solubility and reactivity o Importance in toxicological studies, man vs. mouse 2. High reactivity, low water solubility 3. Low reactivity, no metabolism a. Physical parameters b. Physiological parameters c. Influence of metabolism 4. Quick summary o Application in toxicology 5. Practical use, alveolar air o Example of industrial exposure o Breath analysis 371 794961 0021 IX. Effects on the respiratory tract A. Sensory irritants B. Pulmonary irritants C. Bronchoconstrictors D. Respiratory irritants E. Pulmonary sensitizers F. Tissue reactions 1. Obstructive pulmonary disease, chronic bronchities 2. Centrilobular emphysema 3. Asthma 4. Oxidant injury 5. Pulmonary edema G. Specific Occupational Pulmonary Disease 1. Cadmium and Beryllium 2. Silicosis 3. Silicotuberculosis 4. Asbestosis 5. Coal Worker's pneumoconiosis 6. Kaolin 7. Siderosis, Nickel 8. Metal fume fever, zinc, cadmium 9. Teflon fume fever H. Lung Carcinoma 1. Classification 2. Human Carcinogens 3. Mesothelioma X. Standards for Airborne Contaminants A. Definitions, Promylgating Agencies i) TLV-TWA 372. 794961 0022 ii) TLV (C) ill) STEL iv) PEL v) EEL vi) AQS B. OSHA Health Hazard Categories i) System ii) Examples C. NIOSH/OSHA i) Pocket guide to chemical hazards D. Air Quality Standards E. Establishing TLVs a) Type of data b) Type of effects c) TLV are not toxic indices XI. Federal Hazardous Substances Act a) Toxic b) Highly toxic 794961 0023 373 1 I. DESCRIPTION OF CONTAMINANTS, TERMS USED A. GAS: A STATE OF MATTER IN WHICH THE MOLECULES ARE PRACTICALLY UNRESTRICTED BY COHESIVE FORCES. A GAS HAS NEITHER SHAPE NOR VOLUME FOR OUR USE, IT IS A SUBSTANCE WHICH HAS A CRITICAL TEMPERATURE BELOW 20 C AND THUS CANNOT BE CONDENSED AT ANY PRESSURE AT THIS TEMPERATURE. EXAMPLES: METHANE (-82), FLOURINE (-129) HELIUM (-268). SUBSTANCE DISPERSED IN AIR AS INDIVIDUAL MOLECULES, BELOW ITS CRITICAL TEMPERATURE AND THUS COULD BE CONDENSED TO A LIQUID AT 20 C BY INCREASING THE PRESSURE. THE WORDS VAPOR AND GAS ARE OFTEN USED INTER CHANGEABLY. VAPOR IS MORE FREQUENTLY USED FOR A SUBSTANCE WHICH, THOUGH PRESENT IN THE GASEOUS PHASE AT 20 C, GENERALLY EXISTS AS A LIQUID OR SOLID AT THIS TEMPERATURE AND NORMAL ATMOSPHERIC PRESSURE. EXAMPLES: IODINE (512), BENZENE (289), CARBON DISULFIDE (279). WE CAN ALSO SAY THAT S02 (157), CL2 (.144) NOj (158) AND C02 (289) CAN BE OBTAINED AS ''VAPOR" SINCE AT 20 C THEY CAN BE CONDENSED IN THE LIQUID PHASE BY INCREASING THE PRESSURE. THE DIFFERENCE BETWEEN THE TWO SETS OF EXAMPLES IS SIMPLY THAT FOR THE FIRST SET THEY ARE SOLID OR LIQUID AT ATMOSPHERIC PRESSURE AND 20 C WHILE FOR THE SECOND SET THEY ARE NOT. 374 794961 0024 CJtorAJ tsX n'^rrS MAN. IMPORTANT FOR LARGE PARTICLES. 0 THE LARGER THE PARTICLES ARE ABOVE lum THE MORE CHANCE OF DIFFERENCE IN REGIONAL DEPOSITION WITH MAN. TOTAL NET DOSE MAY BE THE SAME BUT BIOLOGICAL EFFECTS WILL BE DIFFERENT. 0 TO HAVE THE SAME RELATION WITH MAN BETWEEN ATMOSPHERIC PARTICULATE CONCENTRATION AND RATE OF DEPOSITION OF PAR TICLES IN THE LUNGS, FAIRLY UNIFORM PARTICLES AROUND 1-3 um (MMAD) SEEMS TO BE HIGHEST TO USE WITH SMALL RODENTS. Figure 11-11. Deposition of inhaled monodisperse aerosols of fused aluminosilicate spheres in small rodents showing the deposition in the extrathoracic (ET) region, the tracheobronchial (TB) region, the pulmonary (P) region, and in the total respiratory tract based upon Raabe et al. (1977). Compare this figure with the nrevious one given for man. 409 794961 0025 36 MAN VS. LABORATORY ANIMALS IN AEROSOL EXPOSURE WITH LABORATORY ANIMALS IT IS IMPORTANT TO RECOGNIZE THAT ALTHOUGH THE SAME PARTICLE SIZE IS USED, DEPOSI TION AND RETENTION IS LIKELY TO BE DIFFERENT. FEW STUDIES HAVE BEEN MADE (SEE. PALM ET. AL. ARCH. IND. HLTH. _13, 355, 1956, MCMAHON ET AL. INHALED PARTICLES, VOL. TV , 23, 1977). SOME GENERAL CONCLUSIONS: 0 THE MAJOR FACTOR CONTROLLING NET DOSE RECEIVED SEEMS TO BE MINUTE VENTILATION AND THEREFORE THE SMALL ANIMALS WILL RECEIVE A HIGHER TOTAL DOSE BECAUSE OF THEIR HIGHER VENTILATION TO BODY WEIGHT RATIO. HOWEVER THERE IS A LARGE VARIATION BETWEEN ANIMALS OF SAME SPECIES. 408 794361 0026 IMPLICATIONS OF THE MODEL 35 o i z 3 is u 7 9 ? io n a /3 n is Tfeie, Days (HIGH TRANSLOCATION TO BLOOD) c OAfcetfTftftTieAJ, UfiJtTS 407 794961 0027 34 </ 406 794961 0028 VII. RETENTION - CLEARANCE A. MODEL A MODEL PROPOSED BY THE TASK GROUP ON LUNG DYNAMICS IS USED. THIS MODEL INCLUDES THE FOLLOWING AS PRESENTED in THE NEXT FIGURE AND TABLE. B. INPUTS D : TOTAL DUST CONCENTRATION IS INHALED AIR D2: TOTAL DUST CONCENTRATION IN EXHALED AIR D3: TOTAL DUST DEPOSITED IN N-P COMPARTMENT D^: TOTAL DUST DEPOSITED IN T-B COMPARTMENT D$: TOTAL DUST DEPOSITED IN P COMPARTMENT C. ABSORPTION - TRANSLOCATION PROCESSES a: UPTAKE INTO SYSTEMIC BLOOD b: UPTAKE FROM CILIARY MUCUS TRANSPORT c: UPTAKE INTO SYSTEMIC BLOOD d: UPTAKE FROM CILIARY MUCUS TRANSPORT e: UPTAKE FROM DIRECT TRANSLOCATION TO SYSTEMIC BLOOD f: UPTAKE FROM RELATIVELY RAPID CLEARANCE DEPENDENT ON RECRUITABLE MACROPHAGES AND COUPLED TO CILIARY MUCUS TRANSPORT g: UPTAKE MUCH SLOWER THAN f, STILL DEPEND ON ENDOCYTOSIS AND CILIARY - MUCUS FOR CLEARANCE h: UPTAKE BY SLOW REMOVAL VIA LYMPHATIC SYSTEM i: UPTAKE FROM LYMPH TO LYMPH MODES TO BLOOD j: UPTAKE FROM g . i . TRACT TO BLOOD 33 405 794961 0029 32 F /Z flC T /O A J /ty /< C O A i T . / i/ l)i ri.'i'C / L'f\ /;1 lC_.C; l\!z,~T's 404 t 794961 0030 31 VI. CHARACTERISTICS OF THE AEROSOL, INFLUENCING ON TOXICITY WE NEED TO KNOW: 3 1. MASS CONCENTRATION: mg/m , DIRECT SAMPLING, GRAVIMETRIC OR OTHER ANALYSIS 2. SIZE AND DISTRIBUTION SIZE OR MASS ARE GIVEN AS COUNT MEDIAN DIAMETER (CMD) AND MASS MEDIAN DIAMETER (MMD) WITH THE GEOMETRIC STAN DARD DEVIATION (gsd). SINCE TOXICITY IS MORE LIKELY TO BE RELATED TO MASS THE MMD IS THE EXPRESSION OF CHOICE. WE ALSO LIKE TO DEFINE IT AS AN "AERODYNAMIC DIAMETER" WHICH TAKES INTO ACCOUNT SHAPE AND DENSITY OF THE PAR TICLES WHICH INFLUENCE THEIR BEHAVIOR (SEE ABOVE) AND THIS IS OBTAINED EXPERIMENTALLY, 3. SOLUBILITY IN BODY FLUID WILL AFFECT RETENTION, SYSTEMIC EFFECT. STRICTLY SPEAKING IT IS NOT THE SOLUBILITY IN WATER, UNLESS MATERIAL IS HIGHLY WATER SOLUBLE AND NON REACTIVE, BUT INCLUDES OTHER PARAMETERS SUCH AS REACTION WITH BIOLOGICAL MOLECULES WHICH MAY INCREASE TRANSPORT (CARRIERS ETC.) AND WILL ALSO VARY WITH PARTICLE SIZE. THEREFORE THE TERM "TRANSLOCATION" IS MORE APPROPRIATE. 403 794961 0031 c. aerosol: STABLE OR QUASI-STABLE SUSPENSION OF SOLID OR LIQUID PARTICLES IN A GAS. VARIOUS TERMS ARE USED TO BETTER DEFINE AN AEROSOL DEPENDING ON ITS ORIGIN OR STATE. THESE ARE: 2 0 FUMES: SOLID PARTICLES FORMED BY CONDEN SATION GENERALLY USED FOR METALS SUCH AS Cd, Pb, ETC., BUT CAN BE USED FOR ANY SOLID AFTER HEAT TREATMENT SUCH AS TEFLON OR PVC FUMES. USUALLY BELOW lum AND FAIRLY HOMOGENOUS. O DUSTS: SOLID PARTICLES, FORMED FROM DIS INTEGRATION PROCESSES OF A MECHANI CAL NATURE, MINING, GRINDING, ETC. USUALLY ABOVE lum, HETEROGENOUS, UN STABLE, POLYDISPERSED. 0 MISTS: REFER TO LIQUID PARTICLES, FORMED BY CONDENSATION OF A VAPOR (SMALL PAR TICLE HOMOGENEOUS AND STABLE) OR BY ATOMIZATION OF A LIQUID (LARGE PAR TICLE HETEROGENOUS AND LESS STABLE). 0 FOG: A MIST WHICH APPRECIABLY REDUCES VISIBILITY. 0 SMOKE: PARTICLES IN SUSPENSION IN AIR RE SULTING FROM COMBUSTION OR PYROLYSIS OF ORGANIC MATERIALS. COMBINATION OF VAPOR, DUST, FUME, MIST. COMBINATION OF SMOKE AND FOG BUT MORE COMMONLY USED TO DESCRIBE THE RESULTING COMBINATION OF GASES AND AEROSOLS FORMED DURING U-V IRRADIATION OF HYDROCARBONS AND OXIDES OF NITROGEN, OZONE, ETC., L. A . SMOG . 375 794961 0033 0 HOMOGENOUS: 0 HETEROGENOUS: 3 REFERS TO CHEMICAL CONSTITUTION, I.E. SULFURIC ACID. REFERS TO CHEMICAL CONSTITUTION, I.E. COAL DUST. REFERS TO DISTRIBUTION OF PARTICLES AROUND THE GEOMETRIC MEAN OR MEDIAN USUALLY WHEN GEOMETRIC STANDARD DE VIATION ^TT^or LESS AEROSOL IS SAID TO BE MONODISPERSED. AS ABOVE, GEOMETRIC STANDARD DE VIATION LARGER THAN 1.2, HETERODISPERSED ALSO USED. NOTE: AEROSOLS CAN BE HOMOGENOUS AND POLYD ISPERSED, HOMOGENOUS AND HETERODISPERSED, ETC. SOME AUTHORS ALSO USE HOMOGENOUS FOR MONODISPERSED, BE CAREFUL. 376 794961 0034 4 II. CONCENTRATION UNITS A. mg/m3: MILLIGRAMS OF POLLUTANT PER CUBIC METER OF AIR, CAN BE USED FOR GAS, VAPOR, AEROSOL. B. ppm: PARTS PER MILLION = VOLUME OF GAS/VOLUME OF AIR RELATIONSHIP. VOLUME OF VAPOR OR GAS POLLUTANT X TOTAL VOLUME OF CONTAINER OR TOTAL VOLUME OF AIR SAMPLE IQ6 C. VOLUME PERCENT: D. mg/m 3 to ppm= E . ppm to mg/m3 = SAME VOLUME/VOLUME RELATIONSHIP AS ppm, USED FOR HIGH CONCENTRATION, I.E, 1% OR 0.1% INSTEAD OF 10,000 OR 1,000 ppm RESPECTIVELY. mq/m3 x 24.5 = ppm (AT 25C, 760 mmHq ) (22.4 AT 0C, 760 mmHg M.W. ppm - molecular weiqht = mg/m3 (AT 25C, 760 mmHq)(22.4 AT 24.5 0C, 760 mmHg) F. FIBERS/CC NUMBER OF FIBERS/CUBIC CENTIMETER OF AIR, ASBESTOS G. 1 ft3 = 28.32 LITERS 377 794961 0035 H. INDUSTRIAL AND TOXICOLOGICAL APPLICATIONS 0 DILUTION TO TLV ASSUME 1 GRAM OF TOLUENE DIISOCYANATE (TDI), (SPECIFIC GRAVITY % 1.2) EVAPORATES COMPLETELY THRESHOLD LIMIT VALUE (TLV), 1979 IS 0.02ppm, 0.14 mg/m3 FOR DILUTION TO 1 ppm: NEED 141 m3 FOR DILUTION TO 0.02 ppm: NEED 7,000 m3 EQUIVALENT TO A BUILDING OF 30 X 15 X 420 FEET O A LITTLE GOES A LONG WAY ASSUME TDI IS STORED AT ABOUT 100F. WHEN A 55 GALLON DRUM IS FILLED, 55 GALLONS OF "SATURATED" TDI VAPOR ARE LIBERATED. 55 GALLONS 2001 OR 200,000 ml DILUTION TO 1 ppm: NEED 200,000 ml DILUTION 0.02 ppm: NEED107m3, A HUGE BUILDING! 5 378 794961 0036 0 SATURATION CONCENTRATION Ccs:> MW 273 22.4 10 760 mg/m 3 MW: MOLECULAR WEIGHT P : VAPOR PRESSURE (TORR ORmmHg) T: TEMPERATURE K 22.4: VOLUME OCCUPIED BY 1 MOLE OF GAS a 0C,1. FOR TDI, AT 2 5C, = 2 X 10"2 6 r ,rr - 174.2 275 2X10~2 106 ^S^5 ^ 24.5 298 760 171 mg/m3 OR 24.5 ppm. 379 794961 0037 7 III. OTHER CONCENTRATION UNITS A PARTIAL PRESSURE: FRACTION (VOLUME/VOLUME COMPOSITION) OF THE TOTAL PRESSURE OF A MIXTURE EXERTED BY A COMPONENT OF THE MIXTURE. FOR EXAMPLE, AT SEA LEVEL, 1 ATMOSPHERE (760 mmHg, 760 TORRS, 1,013 BAR, 1.03 o kg/cm OR 14.7 p.s.i.a.). IF WE KNOW THE VOLUME COMPOSITION OF EACH COMPONENT IN THE MIXTURE WE CAN CALCULATE THE PAR TIAL PRESSURE OF EACH. ASSUMING THE FOL LOWING COMPOSITION: N2 = 78.6% = 597 mm Hg PARTIAL PRESSURE 2 = 20.8% = 159 mm Hg PARTIAL PRESSURE C02 = 0.04% = 0.3 mm Hg PARTIAL PRESSURE h2o = 0.5% = 3-7 mm Hg PARTIAL PRESSURE TOTAL 100% = 760 mm Hg TOTAL PRESSURE THE VOLUME COMPOSITION CAN BE IN % OR ppm. SEE ABOVE, SINCE BOTH .ARE VOLUME/VOLUME UNIT. THEREFORE, 0.1% OR l,000ppm = 0.76mmHg AT SEA LEVEL. 380 794961 0038 8 B. pV = n RT IF THE CONCENTRATION IS GIVEN AS MOLES/LITER (n/V), THE PARTIAL PRESSURE p(in mm Hg) CAN BE OBTAINED USING THE VALUE OF THE GAS CONSTANT R AS 62 AND THE TEMPERATURE T IN DEGREE KELVIN. HENRY'S LAW THE AMOUNT (MOLES) OF A GAS DISSOLVED IN A LIQUID OSTWALD CO EFFICIENT IS DIRECTLY PROPORTIONAL TO THE PARTIAL PRESSURE 381 794961 0039 IV. ACUTE INHALATION TOXICOLOGY A. LC5Q: ATMOSPHERIC CONCENTRATION, STATISTICALLY ESTIMATED, TO KILL 50% OF THE ANIMALS EX POSED FOR A FIXED TIME, WITHIN A SPECIFIED POST-EXPOSURE PERIOD. || M M I^ 5/10 EXPOSURE RECOVERY 4- 4 I_____ 4 4________________ RECOVERY 5/10 HOUR, RECOVERY 14 DAYS HOUR, RECOVERY 14 DAYS TIME : CONCENTRATIONS FIXED VARIABLE 3 mg/m OR ppm 9 382 794961 0040 B. LT50: TIME FOR 50% OF THE ANIMALS TO DIE AT A PARTICULAR CONCENTRATION. OFTEN USED FOR SATURATED VAPORS, NOT A MEASURE OF TOXICITY. 44444 1 EXPOSURE 1----------------------------------------RECOVERY ^ EXPOSURE , 1 444+4 RECOVERY 5/9 4 + 4- 44 |1 l1 EXPOSURE RECOVERY 5/9 TIME : VARIABLE CONCENTRATION: FIXED FAST ACTING, SLOW ACTING, HAZARD CONCEPT- RESEMBLES ANESTHETIC GASES COMPARISONS ON THEIR POTENCY (mg/ml OF BLOOD) AND SPEED OF INDUCTION (TIME FOR A PARTICULAR LEVEL OF ANESTHESIA). 383 * 794961 0041 11 3 c CONCENTRATION X TIME: LCT50: mg min/m or ppm min USE TO COMPARE APPLES AND ORANGES D. HABER'S RULE, WORKS WITHIN LIMITED RANGE RESPONSE: C T C OR T WITHIN 2 OR 3, WILL NOT WORK WHEN WITH SUBSTANCED HAVING OBVIOUS TRESHOLD (CO) UNLESS QUITE ABOVE TRESHOLD, WORKS BETTER WITH PROGRES SIVE, CUMMULATIVE EFFECT. E. EXPRESSION OF: TOXICITY DOSE :^: NONE OF THE ABOVE, RATHER, INTENSITY OF EXPOSURE IS INVOLVED. HABER' S RULE 5 0% MORTALITY AT 10 mg/m 5 0% MORTALITY AT 5 mg/m 5 0% MORTALITY AT 1 mg/m 10 min. 20 min. 100 min, C T = 100 C T = 100 C T = 100: INCORRECT Further reading on concept of dose in inhalation toxicology: MacFarland, H.N., Respiratory Toxicology, Chapter 5 in Essays in Toxicology, Vol. 7 pp. 121-154, 1976, Academic Press. 384 794961 0042 12 F. BEST: FIX DURATION OF EXPOSURE, ACCORDING TO SITUATIONS (i.e. SPILLS, WORKDAY ETC.) VARIOUS CONCENTRATIONS, TRY TO GET DEATHS TOWARD END OF EXPOSURE OR BEGINNING OF A SHORT POST-EXPOSURE PERIOD (NO MORE THAN 1/3 OF DURATION OF EXPOSURE), CALCULATE LC5Q AND ALSO OBSERVE ANIMALS FOR 14 DAYS AND CALCULATE LC5Q INCLUDING THIS POST-EXPOSURE PERIOD. RATIO OF THE TWO GIVES INDICA TION OF DELAYED TOXICITY. G. SECOND: BEST WHEN IT IS MECHANICALLY IMPOSSIBLE TO GENERATE CONCENTRATIONS HIGH ENOUGH FOR ACUTE TOXICITY DURATION OF EXPOSURE CAN BE INCREASED. HOWEVER COMPARISON OF LC50 FOR TWO MATERIALS WHEN THE DURATION OF EX POSURE IS DIFFERENT BY MORE THAN A FACTOR OF 2 IS RISKY (SEE ABOVE). COMPARING: i) REGARDLESS OF STATISTICAL SIGNIFICANCE, LC5Q FOR LC, TWO MATERIALS ARE COMPARABLE IF WITHIN A FACTOR OF 3. ii) IF ABOVE A FACTOR OF 3: START TO THINK ABOUT IT. iii) IF ABOVE A FACTOR OF 10: WILL DEFINITIVELY MAKE A DIFFERENCE IN REAL LIFE SITUATIONS. J. COMPARING: NO GOOD GENERAL RULE, A FACTOR OF MAYBE 0.5 OF THE LT50 ABOVE. USE LT^ Q TO COMPARE RAPIDITY OF EFFECT OF TWO MATERIALS AT SIMILAR CONCENTRATION OR FOR TWO MATERIALS FOR THE SAME SITUATION, i.e. SATURATED VAPOR, IDEA OF TENABILITY LIMITS. WHEN COMPARING LT50, MAKE SURE THAT YOU ARE COMPARING THE SAME LEVEL OF EFFECT. FOR EXAMPLE, 9g RATS ARE EXPOSED FOR 4 HOURS TO A SATURATED VAPOR ATMOSPHERE OF MATERIAL A AND MATERIAL B. FOR MATERIAL A THE 50th DEATH OCCURRED AT 2 HOURS AND 66 DEATHS OCCURRED BY 4 HOURS. FOR MATERIAL B THE 50th DEATH OCCURRED AT 2 HOURS AND ALL THE ANIMALS WERE DEAD BY 3 HOURS. COM PARING LT50 IS A TRICKY BUSINESS. 385 794961 0043 13 K. COMPARING BOTH LC5Q AND LT^ Q: THIS CAN BE DONE BUT REQUIRES THAT A "STANDARD" BE USED AND THEN COMPARISONS ARE MADE TO THE STANDARD. ANYTHING CAN BE USED AS THE STANDARD OR REFERENCE MATERIAL. FIRST A PERIOD OF TIME MUST BE SELECTED, RELEVANT TO THE SITUATION TO BE INVESTIGATED. IN THE EXAMPLE BELOW 30 MINUTES WAS SELECTED. THEN THE LC50 IS DETERMINED, ARRANGING SO THAT 50% OF THE ANIMALS DIE CLOSE TO THE END OF THAT PERIOD, THE TIME WILL BE THE LT50 (2 2 MINUTES IN THE EXAMPLE GIVEN BELOW FOR WOOD SMOKE AS THE REFERENCE MATERIAL). THEN THE OTHER MATERIALS ARE TESTED. IN THIS PROTOCOL, THE LEVEL OF EFFECT IS FIXED, I.E. 50% LETHALITY AND WE ASK WHAT WILL BE THE CONCENTRATION TO KILL 50% CLC50) AND THE TIME TO DO THIS (LT50). HOWEVER, REMEMBER THAT A FIXED MAXIMUM TIME WAS SELECTED AND THAT RANKING CAN CHANGE IF ANOTHER TIME PERIOD IS SELECTED. THIS CONCEPT OF CONCENTRATION AND TIME DOES NOT BELONG ONLY TO INHALATION EXPERIMENTS. IT IS ALSO OF IMPORTANCE IN CHRONIC STUDIES WHEN CONSIDERING THE DOSE TO PRODUCE 50% EFFECT (ANY EFFECT SUCH AS TUMORS ETC) AND THE TIME REQUIRED FOR THIS GIVEN LEVEL OF EFFECT TO OCCUR. THE SAME APPLIES IN AQUATIC TOXICOLOGY. CONCENTRATION - RESPONSE MUCH MOC; MOtt TOXIC : AS TOXIC 1 ! toxic i WOOO than; than wooo; as wood i 1 1.0 IOO 100.0 1 mimi; 1 111 ii!i|--1 "I'lTniri--1 1000.0 1 11 m:|-- I......... I ' ' "ini___1111 mil Fie. I Each point represents the amount of material (gram on the X a\is) which produced sufficient smo!;e to k*ll of the animals (LC50) and the time (minutes on the Y aaisl required to kill 50% of the animals (LT50) using that amount of maienal. Reading the graph vertically each nta- tenal is classified in terms of potency while each material ts classified ia terms of onset of action by reading horizontally. To combine both, parallel currants separate class A. B. C. and D. For clarity some materials listed in Table 1 have been omitted. However. Table 2 contains tnc results for all materials. From Toxicol. Appl. Pharmacol. 51, 181-188, 1981. 386 794961 0044 14 V. CHAMBER / ^ If V ALL THERE IS TO KNOW ABOUT INHALATION CHAMBERS WAS WRITTEN BY SILVERS IN 1964 (SILVER, S.D. - CONSTANT GASSING CHAMBERS: PRINCIPLES INFLUENCING DESIGN AND OPERATION. J. LAB. CLIN. MED. 31, 1153-1161, 1946). ANYONE STARTING AN INHALATION STUDY WITHOUT READING IT IS MAKING A BIG MISTAKE. A. BEST DESIGN THERE IS NO SUCH THING AS "BEST DESIGN" CHAMBER TO ANSWER ALL THE NEEDS OF INHALATION TOXICOLOGY STUDIES. THE "BEST DESIGN" IS A CHAMBER THAT WORKS ACCORDING TO THE FOLLOWING CRITERIA: 0 FAIRLY UNIFORM DISTRIBUTION OF CONTAMINANTS, VARIATION OF 10-15% BETWEEN SAMPLING PORTS ARE QUITE ACCEPTABLE. 0 AIRFLOW (LITERS/MINUTE) EQUAL TO THE TOTAL VOLUME (LITER) OF CHAMBER IS A GOOD BET TO RUN A CHAMBER, THIS IS GENERALLY SUFFICIENT TO PREVENT TEMPERATURE RISE IF CHAMBER IS CON STRUCTED WITH METAL, KEEP C02 AND AMMONIA LEVEL LOW. AMMONIA LEVEL SHOULD BE VERIFIED WITH HIGH ANIMAL LOAD PARTICULARLY WHEN REACTION WITH POLLUTANTS IS POSSIBLE, Cl2, S02, N02, ETC. IF THIS AIRFLOW PRESENTS A PROBLEM (HIGH COST OF POLLUTANT, AVAILBILITY OF POLLUTANT, CLEANING, ETC) IT CAN BE REDUCED BUT PROBABLY NOT BELOW 0.2 THE TOTAL VOLUME OF THE CHAMBER WITHOUT CREATING PROBLEMS WITH TEMPERATURE, AMMONIA, ETC. MacFarland has reviewed Sliver's article and expanded it, see previous page for reference. 387 794961 0045 15 0 ANIMAL LOAD SHOULD BE LOWER THAN 1% TO 5% OF CHAMBER VOLUME. CALCULATE AS FOLLOWS: TAKE BODY WEIGHT OF EACH ANIMAL TO BE SAME AS ITS VOLUME (l.e. 200 GRAMS RAT = .2 LITER) AND MULTIPLY BY NUMBER OF ANIMALS. THUS TO EXPOSE 100 RATS OF 200 GRAMS (20 LITERS OF RATS) YOU NEED A CHAMBER VOLUME OF MINIMUM 2,000 LITERS AND PREFERABLY THERE, WILL BE ONLY ONE LAYER.OF ANIMALS. THIS CAN BE REDUCED TO A 400 LITER CHAMBER (5%) BUT LIKELY TO NEED 2 LAYERS. THIS ONE LAYER IS PRE FERABLE IF-WORKING WITH HIGHLY REACTIVE GASES WHICH WILL REACT WITH FUR OF ANIMALS OR WITH LARGE PARTICLES BUT IS NOT NECESSARY WITH AREOSOL AROUND lum AND WITH NON REACTIVE GASES SUCH AS CO ETC. OR VAPORS SUCH AS BENZENE, CARBON TET RACHLORIDE ETC. O DO NOT USE THE CHAMBER FOR MIXING. THE ADDED POLUTANT SHOULD BE MIXED WITH THE INCOMING DILUTING AIR IN A MIXING DEVICE PRIOR TO ENTERING THE CHAMBER OR MIXED AT THE TOP OR ENTRANCE OF THE CHAMBER. THE IDEA OF PLACING BAFFLES ETC. IN A CHAMBER FOR BETTER MIXING IS ABSURD. THE GOLDEN RULE: MIX YOUR MARTINI BEFORE YOU DRINK IT, NOT AFTER. O DO NOT USE FAN IN A CHAMBER FOR MIXING A FAN WILL CREASE TURBULANCE WHICH WILL INCREASE AEROSOL COAGULATION AND STRATIFI CATION. 387a 794961 0046 16 0 WITH REACTIVE GASES "CONDITIONING" OF THE CHAMBER SHOULD BE DONE PRIOR TO LOADING ANIMALS IN THE CHAMBER. ONCE THIS IS DONE ADDITION OF ANIMALS WILL DROP THE CONCENTRA TION BY AT LEAST 50% AND SOMETIMES BY AS MUCHAS 95%. THIS IS NOT SERIOUS FOR A LONG-TERM CHRONIC STUDY. INDEED DURING THE FIRST WEEK OF SUCH STUDY ADJUSTMENT CAN BE MADE TO THE DELIVERY SYSTEM TO BRING THE CONCENTRATION UPWARD TO THE DESIRED LEVEL. IN CASES OF ACUTE' STUDIES, IF YOU WANT TO KNOW WHAT THE ANIMALS ARE LIKELY TO "SOAK" COLLECT DEAD ANIMALS, KEEP THEM REFRIGERATED AND THEN PLACE IN YOUR CHAMBER. THERE WILL BE NO DIFFERENCE BETWEEN LIVE AND DEAD ANIMALS SINCE THE AMOUNT OF POLLUTANT INHALED BY THE LIVING ANIMALS IS EXTREMELY SMALL, THE MAJOR CONTRIBUTION COMES FROM REACTION WITH THE FUR. PROBABLY THE BEST DESIGN IS HEAD ONLY EXPOSURE. 0 PERMITTED DAILY VARIATION REACTIVE GASES NON-REACTIVE GASES AEROSOL < 1 um AEROSOL 1-5 um % 20% OF DESIRED % 15% OF DESIRED % 20% OF DESIRED % 20% OF DESIRED DON'T USE THEM IN LARGE CHAMBER, HEAD ONLY EXPOSURE, RELEVANCE IS IN QUESTION. RATS DO NOT INHALE ROCKS! CONSUMER SPRAY CAN PRODUCTS. SPRAY PAINTS. POSSIBLY: REDUCE TO SMALLER SIZE SET-UP ELUTRIAT I ON SYSTEMS. 388 794961 0047 17 B. DESIGN FOR VERY HIGH LEVEL OF AEROSOL EXPOSURE THE DECISION TO USE A CHAMBER OR HEAD ONLY EXPOSURE IS IM POSSIBLE TO MAKE WITHOUT SOME PRELIMINARY WORK WITH MATERIAL. THIS WORK CAN BE DONE USING A SMALL CHAMBER AND A FEW ANIMALS. 3 IN GENERAL CONCENTRATION OF > THAN 50 mg/m ARE DIFFICULT TO WORK WITH UNLESS THE PARTICLE SIZE IS SMALL, HEAD ONLY EXPOSURE IS INDICATED. THIS PRESENTS SOME PROBLEMS, CAGE CONTROL AND HEAD ONLY EXPOSURE CONTROL MUST BE USED, HIGH LABOR, BUT IT CAN BE DONE WELL AND HAS BEEN DONE WELL. THERE HAS BEEN SOME TALK ABOUT AN EPA RECOMMENDED LEVEL OF 5 GRAM/ LITER OF AEROSOL. THIS IS IMPOSSIBLE TO ACHIEVE FOR MOST SOLID OR LIQUID AND KEEPING THE PARTICLE SIZE REASONABLY SMALL FOR RATS TO INHALE AND AT THE SAME TIME USING AN INHALATION CHAMBER. DON'T WASTE YOUR TIME TRYING THIS. 794961 0048 389 18 C. CHEAP CHAMBER, GOOD RESULTS FOR ACUTE OR SUB-ACUTE WORK USING 10-20 RATS OR 20-50 MICE AN ALL-GLASS 100-LITER AQUARIUM IS JUST PERFECT. A COVER CAN BE MADE OUT OF PLYWOOD OR PLEXIGLASS WITH THE INSIDE OF THE COVER LINED WITH TEFLON. SUCH A CHAMBER COST ABOUT $100 WITH ALL FITTINGS. OPERATED AT 100 LITERS/MIN EQUILIBRIUM CONCENTRATION WILL BE REACHED IN ABOUT 5 MINUTES WITH UNIFORM DISTRIBUTION OF CONTAMINANTS, GASES OR AEROSOLS. CSEE TAP, 49, 89-95, 1979) J------------ 1 794961 0049 390 19 D. VERY SHORT EXPOSURE ClO-15 MINUTES) FOR VERY SHORT-EXPOSURE A CHAMBER OPERATED AS ABOVE WOULD BE INAPPROPRIATE UNLESS THE AIRFLOW WAS RAISED TO ABOUT 500 LITERS/ MINUTE TO REDUCE EQUILIBRATION TIME. THIS MAY PRESENT SOME PRO BLEMS. INSTEAD A CHAMBER HAVING A VOLUME OF 10 LITERS CAN BE MADE OUT OF A GLASS CYLINDER AND USE FOR HEAD ONLY EXPOSURE WITH AN AIRFLOW OF 50 LITERS/MINUTE. 1977). CSEE ARCH. ENV. HLTH. 32., 68-76, c- C 794961 0050 391 20 E. DON'T EXPOSE ANIMALS UNLESS YOU ARE SURE PRIOR TO EXPOSING ANIMALS YOU SHOULD HAVE GOOD EXPERIENCE WITH AN EMPTY CHAMBER, INCLUDING THE HOUSING CAGES,. YOU SHOULD KNOW HOW LARGE A DIFFERENCE THERE IS BETWEEN THE NOMINAL CONCENTRA TION AND ACTUAL CONCENTRATION. NOMINAL CONCENTRATION = AGENT FLOW IN MILLIGRAMS/MINUTE AIRFLOW IN LITERS/MINUTE ACTUAL CONCENTRATION = OBTAINED FROM SAMPLING AND ANALYSIS 392 . 794961 0051 RAPID GUIDE FOR EQUILIBRATION TIME AND ITS USE AS A GAS OR AEROSOL IS INTRODUCED AT A UNIFORM RATE IN THE CHAMBER MAINTAINED AT A CONTINUOUS FLOW THE CONCENTRATION WITHIN THE CHAMBER INCREASES UNTIL IT IS PRACTICALLY CON STANT. ASSUMING PERFECT MIXING -bt C = j (1-e 3 ) (1) 21 C = CONCENTRATION IN mg/1 iter AT TIME t W = MILLIGRAMS OF AGENT INTRODUCE/MINUTE a = VOLUME OF THE CHAMBER IN LITER b = VOLUME OF AIR THROUGH THE CHAMBER IN LITERS/MIN. e = THE BASE OF NATURAL LOG, 2.7182 THUS THE % OF THE DESIRED CONCENTRATION OBTAINED IN TIME t IS: -bt t = 100 (1-e a ) (2) THE TIME REQUIRED FOR EQUILIBRATION OF THE CHAMBER TO 99% CAN BE CALCULATED BY SETTING EQUATION 2 EQUAL TO 99 -bt -bt 99 = 100 (1 -e 3 ) OR e a = 1-Q--1~Q" = .01 TRANSFORMED INTO LOGARITHM FORM - = In 0.01 = -4.6052 (3) tgg SHOULD BE CALCULATED FOR EACH SITUATION SO THAT THE TIME TO REACH EQUILIBRATION I`S VERY SHORT COMPARED TO THE DURATION OF EXPOSURE. I'-* ;U---------------Y--------------------y THUS WHEN a AND b ARE EQUAL X IS ABOUT 5 MINUTE. 393 794961 0052 22 G. AIR CHANGES AN AIR CHANGE IS SAID TO OCCUR WHEN A VOLUME OF AIR EQUAL TO THE VOLUME OF THE CHAMBER HAS PASSED THROUGH THE CHAMBER. THIS IS A CONVENIENT TERM FOR VENTILATION ENGINEERS BUT IS NOT STRICTLY SPEAKING CORRECT. WHEN SUCH OCCURS, FROM EQUATION 2, ONLY 63% OF THE AIR HAS BEEN "CHANGED". FROM EQUATION 3, THE TIME FOR ONE "AIR CHANGED" MUST BE MULTIPLIED BY A FACTOR OF 4.6 BEFORE EVEN 99% OF THE EXPECTED CHANGE CAN BE DONE. THEREFORE IF a AND b ARE EQUAL THERE IS ONE "AIR CHANGE" EVERY 4.6 MINUTES OR 12/ HOUR. THE BEST THING TO DO IS TO FORGET ABOUT "AIR CHANGE" AND GIVE a AND b. THEN WE KNOW. 394 794961 0053 VI. -FACTORS INFLUENCING THE DOSE FOR AEROSOLS 0 A. FACTORS INFLUENCING TOTAL DOSE 3 i) CONCENTRATION IN AIR, C, mg/m OR mg/1 ii) PARTICLE SIZE, a, WHICH WILL DETERMINE THE FRACTION OF AEROSOL DEPOSITED" lii) MINUTE VENTILATION, MV, WHICH IS DETERMINED BY TIDAL VOLUME (VT) AND NUMBER OF BREATH PER MINUTE (f) iv) DURATION OF EXPOSURE IN MINUTES (t) V) BODY WEIGHT,kg USEFUL VALUES AT REST SPECIES MAN (70kg) MOUSE (.02 kg) RAT (.2 kg) GUINEA-PIGS (.2 kg) MONKEYS (3 kg) MAN (MODERATE EXERCISE) VT (ml) 800 0.1 - 0.2 2 2 40 1,450 f 15 250 120 . 120 35 15 :: DEPOSITION: ALL FACTORS WHICH DETERMINE WHAT FRACTION OF THE INSPIRED AEROSOL WILL BE CAUGHT IN THE RESPIRATORY TRACT (NOSE TO ALVEOLI) AND FAIL TO EXIT WITH THE EXPIRED AIR. 0 REQUIRED READING FOR ANYONE PLANNING TO WORK WITH AEROSOLS: DEPOSITION AND RETENTION MODELS FOR INTERNAL DOSIMETRY OF THE HUMAN RESPIRATORY TRACT. TASK GROUP ON LUNG DYNAMICS HEALTH PHYSICS _1_2, 173-207, 1966. RECENT REVIEW: J.D. BRAIN AND P.A. VALBERG, AMER. REV. RESP. DISEASE .120., 132 51373, 1979. 23 395 794961 0054 REMEMBER: THIS GIVES ONLY TOTAL DEPOSITED. DOES NOT GIVE REGIONAL DEPOSITION WHICH IS HIGHLY IMPORTANT. THIS DOES NOT TAKE CLEARANCE INTO ACCOUNT. TO GET A "BALL PARK" FIGURE, ASSUME 50% CO.5) FOR a THUS: AS CAN 0.5 X 8 00ml BE SEEN, WE X J_5_ X 1 mg X 60 min min 1,000 ml 70 kg ------------- = mg/kg NOW HAVE THE PROPER UNITS FOR TOXICITY INSTEAD OF JUST HAVING AN EXPOSURE CONCENTRATION IN mg/1 OR mg/m3. COMPARISONS OF TOTAL DOSE RECEIVED CAN BE MADE BETWEEN VARIOUS ANIMALS, EXPOSED AT THE SAME CONCENTRATION, ON THE BASIS OF mg/kg OF BODY WEIGHT OR mg/m2 OF BODY SURFACE AREA. 396 794961 0055 25 B. FACTORS AFFECTING REGIONAL DEPOSITION: SIZE, SHAPE, DENSITY i) SEDIMENTATION (GRAVITY), SETTLING ALL PARTICLES WITH DENSITY GREATER THAN AIR EXPERIENCE A DOWN WARD FORCE DUE TO GRAVITY F grav = V part (D part - D air) g V part = VOLUME OF THE PARTICLE D = DENSITY g = GRAVITATIONAL ACCELERATION THUS THE PARTICLE ACCELERATES DOWNWARD UNTIL ITS VELOCITY IN CREASES TO THE POINT WHERE THE RETARDING FORCE DUE TO ITS MOTION THROUGH AIR JUST BALANCES ITS WEIGHT. IF PARTICLE IS SPHERIC AND SMALL ENOUGH SO THAT VISCOUS FORCES ARE THE PRIMARY RESISTIVE FORCES STOKE'S LAW APPLIES TO PREDICT RETARDING FORCES. F resist = 3 ir d n v d = DIAMETER OF PARTICLE n = VISCOSITY OF AIR V = VELOCITY OF THE PARTICLE THE VELOCITY AT WHICH THIS RESISTIVE FORCE EQUALS THE GRAVITA TIONAL FORCE IS THE TERMINAL VELOCITY, VT VT = (D part - D air) qd^ 18n EXAMPLE: 1 urn PARTICLE, D = 1 , VT = 33 um/s AND WOULD BE ESTABLISHED IN 10 US FOR PARTICLE STARTED FROM REST. APPLIES TO PARTICLES 1-40 um, CORRECTION CAN BE MADE FOR 0.001 um TO 200 um BUT NOT RELEVANT FOR OUR USE. FOR NON-SPHERICAL PARTICLES THIS CANNOT BE CALCULATED BUT MEASURED EXPERIMENTALLY AND CHARACTERIZED AS "AERODYNAMIC DIAMETER", IT HAS THE SAME SETTING VELOCITY OF A UNIT-DENSITY SPHERE. 397 794961 0056 26 11 ) IMPACTION, INERTIA WHEN AN OBSTACLE IS PLACED IN THE PATH OF THE AIRFLOW OR BIFURCATIONS OR TORTUOUS PATHS SUCH AS IN THE NOSE OR TRACHEO-BRONCHIAL TREE ARE PRESENT SMALL PARTICLES WILL FOLLOW THE GAS FLOW LINES BUT LARGE PARTICLES, BECAUSE OF GREATER INERTIA ARE UNABLE TO CHANGE DIRECTION AND WILL IM PACT ON THE SIDE. IMPACTION WILL DEPEND ON 4 FACTORS 0 AIR VELOCITY 0 DENSITY OF THE PARTICLE 0 SQUARE OF THE PARTICLE DIAMETER 0 ANGLE OF AIRSTREAM DEFLECTION IMPORTANT: > 3 um, NASOPHARYNGEAL AREA, CENTRAL AIRWAYS 398 794961 0057 27 i) DIFFUSION, BROWNIAN MOVEMENT MOTION CAUSED BY RANDOM MOLECULAR COLLISION THIS PROCESS CAN BE DESCRIBED AS FOLLOWS: A = /FEft A: ROOT-MEAN SQUARE DISPLACEMENT AFTER A TIME, t D: DIFFUSION COEFFICIENT COEFFICIENT OF PARTICLES WHICH IS EXPRESSED AS FOLLOWS: 3n nd T: TEMPERATURE, KELVIN k: BOLTZMANN CONSTANT Cl.38 X 10~16 ergs/K) n: GAS VISCOSITY d: DIAMETER OF PARTICLE IT IS IMPORTANT FOR PARTICLES < 1 Util. IMPORTANT TO REMEMBER THAT PARTICLE DIAMETER IS THE PRIMARY FACTOR. 399 794961 0058 28 ABOUT THE EFFECT OF CHARGE. ----------------- v) INTERCEPTION OF IMPORTANCE FOR FIBERS AS THE INSPIRED AIR COMES IN CLOSE CONTACT WITH A SURFACE. FIBER DEPOSITION MODELS ARE MUCH LESS WELL DEVELOPED THAN FOR PARTICLES. 400 794961 0059 VI. QUICK SUMMARY " DIRECTIONAL CHANGES VERY ABRUPT REGIONS AND MECHANISMS OF DEPOSITION LESS ABRUPT MILD :: FROM CASSARETT 29 AIR VELOCITY ++++ +++ ++ + 0 401 794961 0060 45 l / / WATER: FAT : 40 LITERS 15 LITERS 417 794961 0061 416 794961 0062 43 3. LOW REACTIVITY WITH SURFACE OF RESPIRATORY SYSTEM, ASSUME INERT GAS AND NO METABOLISM, USE THE FOLLOWING SYSTEM: " A: PHYSICAL PARAMETERS i) CONCENTRATION IN AIR (mmHg) DETERMINES MAXIMUM CONCENTRATION (mmHg) IN BLOOD SINCE EQUILIBRIUM WILL BE ESTABLISHED AT THE . SOME TIME. ii) KNOWING S GIVES THE MAXIMUM CONCENTRATION IN MOLES OR MILLIGRAMS/LITER OF BLOOD WHICH CAN BE ACHIEVED, i.e. AT EQUILIBRIUM. i i i) SUBSTANCES WITH HIGH S WILL TAKE A LONG TIME TO REACH EQUILIBRIUM (METHANOL, ETHANOL, ACETONE, ETHER, ETC.). SUBSTANCES WITH LOW S (METHANE, ETC.) WILL REACH EQUILIBRIUM VERY QUICKLY. BE TAKEN FOR WATER AT 37C. S VALUE CAN B: PHYSIOLOGICAL PARAMETERS i) MINUTE VENTILATION: IMPORTANT FOR HIGH S SUBSTANCES ii) CARDIAC OUTPUT: IMPORTANT FOR LOW S SUBSTANCES i i i) AMOUNT OF BLOOD TO BE SATURATED, 5 LITERS AND TOTAL BODY WATER,40 LITERS. iv) OIL/WATER PARTITION COEFFICIENT: FROM BLOOD TO TISSUES Source: Goldstein et. al., Principles of drug action. 415 794861 0063 Dose (M g/crrr/breath) 0 5 10 15 20 25 Model Segments Firjure 4. Reprinted from McJilto.n, C., ThielRc, J., and FranR, R., 1972. 414 79496A 0064 41 Mass Uptake (ug) during first breath Model Segmenrs Figure 3. Reprinted frou /IcJi1 ton. C., Thielkc, J.. and Frank, P... 1972. 413 794961 0065 2. HIGH REACTIVITY, LOW WATER SOLUBILITY. THESE WILL PENETRATE DEEPER INTO THE LUNG, N02, 0 COCl2, TDI, REACT WITH PULMONARY TISSUES, GENERALLY PRODUCE EDEMA. CALCULATE LIKE AEROSOL, ASSUME 100% FOR a . 40 412 794961 0066 H. Lucia, C. S. Barrow, M. F. Stock and Y. Alarie a messing Damage Sustained by Upper Respiratory Tract of Laboratory Mouse 39 SECTION 2 - RESPIRATORY rOlfoctory Mucosa Figure t. Pertsegitel view of the note, showing the sections used in proceasing and for microscopic examination. SECTION I EXTERNAL NARES Figure 3. Coronal section *2, normal anatomy. SECTION 3 Cartiloge-- Notoi 0on Pstudostrofified Columnar Epithet Antcriormost Ethmoid Turbinate /Olfoctory Mgcoio Nosoturbmote Mojullory bone Figure 2. Corona/ section * 1, norma/ anatomy. H. Lucia, C. S. Barrow, M. F. Stock and Y. Alarie SECTION 4 Venous Sinus Poiote Figure 4. Coronal section ^-SQuomous Epithelium normal anatomy. Figure 5. Corona/ section =4, normal anatomy. 411 Table 1. Rating System for Evaluation of the Damage Due to Exposure to Airborne Chemicals in the Upper Respiratory Tract of Mice. 0 no damage seen at 24 hours I* 1-50* of the mucosa is damaged, but underlying tissues are intact 2* 25-75? of the mucosa is destroyed, and some damage to the submucosa is noted 3* 50-99? of the mucosa is destroyed, and mere is damage to the submucosa and underlying Support structures 4* 100? of tne mucosa is destroyed and there is extensive destruction of all underlying tissues 794961 0067 38 VIII FACTORS INFLUENCING THE DOSE FOR GASES, VAPORS :: 1. HIGH WATER SOLUBILITY AND REACTIVITY. FOR THESE GASES, S02, HCl, HF, HCHO, CALCULATE LIKE AEROSOL ASSUME 100% FOR a. ESSENTIALLY COMPLETELY REMOVED BY SOLUTION AND REACTION AT THE SURFACES OF THE RESPIRATORY TRACT AND VERY EFFICIENTLY SCRUBBED BY THE UPPER RESPIRATORY TRACT, VERY LITTLE PENETRA TION TO THE ALVEOLAR REGION UNTIL HIGH CONCENTRATIONS ARE REACHED. FEW GASES HAVE BEEN INVESTIGATED FOR RE GIONAL PENETRATION, S02, Oj, SEVERAL ALDEHYDES. HIGH WATER SOLUBILITY DOES NOT SEEM TO BE SUFFICIENT SINCE ACETONE IS NOT ENTIRELY REMOVED BY THE NOSE WHILE S02 IS. WITH S02 THE REACTION WITH WATER AT pH 7.4 WILL YIELD S02 + H20 Z H2S03 Z H+ + HSO3'" HSO3- t H+ + S03= THEN REACTION OF HSO3- AND S03= WITH PROTEIN DISULFIDE BONDS TO YIELD SULFONATES. SIMILAR SCHEMES CAN BE PRESENTED FOR SEVERAL WATER SOLUBLE AND REACTIVE CHEMICALS. 0 IMPORTANCE IN TOXICOLOGICAL STUDIES: SINCE MICE, RATS, GUINEA-PIGS, HAMSTERS ARE OBLIGATORY NOSE BREATHERS, THE FIRST AREA AFFECTED BY THESE GASES WILL BE THE NOSE. NASAL CARCINOMA IN RATS AND MICE DUE TO FORMALDEHYDE IS A GOOD EXAMPLE. 794961 0068 410 5. 'PRACTICAL USE OF THE CONCEPT (ADAPTED FROM R.D. STEWART) 0 BLOOD CONCENTRATION = ALVEOLAR AIR CONCENTRATION X S HUMAN EXPOSURE TO TRICHLORETHYLENE, 200 ppm, 7 HRS/DAY FOR FOR 5 DAYS 47 PRE-EXPOSURE (MORNING) 3 HOURS 30 MIN AFTER LUNCH 7 HOURS 1 HR. POST EXPOSURE 3 HR. POST EXPOSURE 6 HR. POST EXPOSURE ALVEOLAR AIR CONCENTRATION (ppm) 1ST DAY 2ND DAY 3RD DAY 4TH DAY 5TH DAY 0.01 76 10.3 76 8.3 5.1 3.3 1.2 75 10.9 75 9.4 4.4 2.8 1.6 76 11.5 76 9.0 3.5 2.4 1.6 79 8.4 79 7.7 3.5 2.9 1.6 76 8.5 76 8.7 3.6 2.9 90 HRS. POST-5 DAY EXPOSURE: 0.2 DOES NOT REACH EQUILIBRIUM WITH INSPIRED AIR NO CUMMULATI ON INCOMPLETE RELEASE 0 ALCOHOL BREATH TEST ANALYSIS TO DETERMINE THE BLOOD CONCENTRATION FROM A SAMPLE OF ALVEOLAR AIR. SINCE ALVEOLAR AIR IS AT EQUILIBRIUM WITH CAPILLARY BLOOD, BY KNOWING THE AMOUNT IN ALVEOLAR AIR AND THE SOLUBILITY COEFFICIENT ONE KNOWS THE CONCENTRATION IN THE BLOOD. 419 794961 0069 46 4. QUICK SUMMARY CADAPTED FROM A. GOLDSTEIN ET AL.) AGENT S ETHYL ETHER 15 CHLOROFORM 7.3 HALOTHANE 2.5 X 1.0 NITROUS OXIDE 0.5 EHTYLENE 0.15 TIME TO EQUILIBRIUM SLOW \l' FAST QUANTITY IN MOLES LARGE \V SMALL PHYSIOLOGICAL FACTOR LIMITING UPTAKE VENTILATION / 50/50 ' CARDIAC OUTPUT o A^ *v>~ ; 4/*- V5. Mou^C 794961 0070 418 48 EFFECTS ON THE RESPIRATORY TRACT " A - SENSORY IRRITANT i) DEFINITION CHEMICAL WHICH WHEN INHALED VIA THE NOSE WILL STIMULATE TRIGEMINAL NERVE ENDINGS, EVOKE A BURNING SENSAT I ON OF THE NASAL PASSAGES AND INHIBIT RESPIRATION. ALSO MOST WILL INDUCE COUGHING FROM LARYNGEAL STIMULATION. il) OTHER CHARACTERISTICS: THESE CHEMICALS ARE ALSO CAPABLE OF STIMULATING TRIGEMINAL NERVE ENDINGS OF THE CORNEA AND INDUCE TEARING. AT HIGH CONCENTRATION, PARTICULARLY ON MOIST FACIAL SKIN, THEY ARE CAPABLE; OF INDUCING A BURN ING SENSATION. SOME HAVE ODORANT AND/OR GUSTATORY QUALITIES. MOST WILL INDUCE BRONCHOCONSTRICTION, USUALLY AT CONCENTRA TIONS IN THE AIR HIGHER THAN REQUIRED FOR STIMULATION OF NERVE ENDINGS IN THE NASAL PASSAGES. iii) EQUIVALENT TERMS TO DESCRIBE THEIR ACTION: UPPER RESPIRATORY TRACT IRRITANT, NASAL OR CORNEAL TRIGEMINAL STIMULANT, COMMON CHEMICAL SENSE STIMULANT, CHEMOGENIC PAIN STIMULANT, SUFFOCANT, LACHRYMATOR, STERNUTATOR. iv) TYPICAL EXAMPLES: CHLORACETOPHENONE, 0-CHLOROBENZYLI DENE MALONONITRILE, B-NITROSTYRENE, DIPHENYLAMINOCHLOROARSINE, SULFUR DIOXIDE, AMMONIA, ACROLEIN, FORMALDEHYDE. Practical, Industrial Classification for A,B,C,D. - From Alarie, CRC, Crit. Rev. Toxicol.., 2, 2 99, 1 973. 420 794961 0071 49 B - PULMONARY IRRITANT i) DEFINITION: CHEMICAL WHICH WHEN INHALED WILL STIMULATE SENSORY RECEPTORS WITHIN THE LUNG AND INCREASE RESPIRATORY RATE WITH A DECREASE IN TIDAL VOLUME RESULTING IN RAPID SHALLOW BREATHING. THEIR ACTION, AS OPPOSED TO THAT OF SENSORY IRRITANTS, OR BRONCHOCONSTRICTORS EVOKE A SENSATION OF DYSPNEA AND BREATHLESNESS RATHER THAN A CONSCIOUS PAINFUL SENSATION. ii) OTHER CHARACTERISTICS: THESE CHEMICALS ARE CAPABLE OF INDUCING PULMONARY EDEMA WHICH IS THEN ACCOMPANIED BY PAINFUL BREATHING. THEY HAVE NO OR LITTLE ACTION AS SENSORY IRRITANTS OF THE EYE OR NASAL PASSAGES AT CONCENTRATION SUFFICIENT FOR PULMONARY IRRITATION AND, THEREFORE THEY PROVIDE LITTLE WARNING OF THEIR PRESENCE. SOME HAVE ODORANT OR GUSTATORY QUALITIES AND SOME EXERT A BRONCHOCONSTRICTING ACTION. iii) EQUIVALENT TERMS TO DESCRIBE THEIR ACTION: LOWER RESPIRATORY IRRITANT, LUNG IRRITANT, DEEP LUNG IRRITANT. iv) TYPICAL EXAMPLES: PHOSGENE, NITROGEN DIOXIDE, SULFURIC ACID MIST, OZONE, SULFUR AND NITROGEN MUSTARD, SULFUR PENTAFLUORIDE, CADMIUM FUMES. 421 794961 0072 50 C - BRONCHOCONSTRICTORS i) DEFINITION: CHEMICAL WHICH WHEN INHALED WILL INDUCE AN INCREASE IN RESISTANCE TO AIRFLOW WITHIN THE CONDUCTING AIRWAYS OF THE LUNG. THE ACTION CAN BE VIA DIRECT EFFECT ON SMOOTH MUSCLES OF THE CONDUCTING AIRWAYS, BY AXONAL REFLEX, BY VAGO-VAGAL OR TRIGEMINAL-VAGAL REFLEXES FOLLOWING STIMULATION OF NERVE ENDINGS BELONGING TO THESE SYSTEMS OR BY LIBERATION OF HISTAMINE. ii) OTHER CHARACTERISTICS: MOST OF THESE CHEMICALS ARE ALSO SENSORY IRRITANTS. THEIR ACTION ON THE BRONCHIAL,MUSCOSA PRODUCES A PAINFUL SENSATION. iii) TYPICAL EXAMPLES: SULFUR DIOXIDE, AMMONIA, INERT PARTICLES, SEN SITIZATION BY ALLERGENS SUCH AS FOREIGN PROTEINS OR CHEMICALS ACTING AS HAPTEN SUCH AS TOLUENE DI ISOCYANATE, AEROSOLS OF HISTAMINE OR CHOLINERGIC AGONISTS. 422 794961 0073 51 D - RESPIRATORY IRRITANTS i) DEFINITION: CHEMICAL WHICH WHEN INHALED CAN ACT AS SENSORY IRRITANT, BRONCHOCONSTRICTOR AND PULMONARY IRRITANT. THESE CHEMICALS ARE CAPABLE OF ALL THREE ACTIONS AND THERE IS LITTLE DIFFERENCE BETWEEN THE CONCENTRATION AT WHICH THEY ARE SENSORY IRRITANT AND PULMONARY IRRITANTS. ii) OTHER CHARACTERISTICS: IRRITANTS. SIMILAR TO SENSORY IRRITANTS AND LUNG iii) EQUIVALENT TERM TO DESCRIBE THEIR ACTION: ANY OF THE TERMS MEN TIONED IN THIS TABLE, DEPENDING ON THE EXPOSURE CONDITIONS IN VOLVED. iv) TYPICAL EXAMPLES: CHLORINE, KETENE, CHLOROPICRIN, DICHLOROMETHYL ETHER, CHLORINE PENTAFLUORIDE, DI EPOXYBUTANE. 423 794961 0074 52 E. PULMONARY SENSITIZERS (HYPERSENSITIVITY, DIFFERENT FROM HYPERSUSCEPTIBILITY) i) definition: chemicals which when inhaled stimulate immuno logic SYSTEM SUCH THAT UPON RE-EXPOSURE TO A VERY LOW CON CENTRATION A PULMONARY REACTION OCCURS. a) FOREIGN PROTEINS: DEPENDENT ON MOLECULAR WEIGHT EXAMPLE: SUBTI LISINS (PROTEOLYTIC ENZYMES) TLV = 6 x 10"5 mg/m3 - jUfllW b) SIMPLE CHEMICALS WHICH ACT AS HAPTENS." HAPTEN: ANY SMALL MOLECULE WHICH WHEN ATTACHED TO A MACROMOLECULE INDUCES FORMATION OF ANTIBODIES TO THE CHEMICAL AND WHICH CAN REACT WITH SPECIFIC ANTIBODIES. EXAMPLE: TOLUENE DIISOCYANATE (TDI), TRIMELLITIC ANHY DRIDE, POTASSIUM CHLOROPLATINATE, PHTALLIC ANHY DRIDE. -I i ) TYPE OF PULMONARY REACTIONS a) IMMEDIATE HYPERSENSITIVITY: ASTHMA ATTACK, OCCURS WITHIN 1 HR OF EXPOSURE, CLASS OF ANTIBODY RESPONSIBLE MAINLY lgE ALSO 1 gG4 POSSIBLY OTHERS. b) LATE REACTION: STARTS AFTER 1 HR., LAST 2-3 HRS. OR START AFTER 3-4 HRS. LAST 24-36 HRS. MAINLY lgG PRECIPITATING ANTIBODIES. BIRD FANCIERS DISEASE, FARMER'S LUNG DISEASE (THERMOPHYLLIC ACTINOMYCETES) ALLERGIC ALVEOLITIS. C) GRANULOMA FORMATION: CELL-MEDIATED MECHANISM INSTEAD OF ANTIBODIES. TUBERCULOSIS, BERYLLIUM. 424 794361 0075 / < >*< 4 53 Table I. Respiratory Hypersensitivity from Industrial Chemicals Industrial Compound Symptoms Reference Amprolium hydro chloride -- Beryllium Asthma ` fT Rhinitis, cough, -- -dyspnea, cyano sis ! Greene and Freedman, 1976 Hardy and Tabershaw, - 1946 !Cement dust i [Chloramine _ _ ! Diphenylme thane . . _ diisocyanate 02)1) Asthma ' I Asthma ( iEnflurane i Asthma Kobayashi, 1974 Boupie e_t al., 1979 _Zeiss et_ al., 1980: Konzen e_t al^., 1966 Schwettmann and Casterline, 1976 Ethylenediamine Asthma Lam and Chan-Yeung, 1980 .Formalin Asthma Hendrick and Lane, 1975 Haphthylene diisoj cyanate As thma Harries et al., 1979 . Hickel sulfate Persulfate salts Phenvlglycine acid chloride Phenylmercuric proprionate 'Phthalic anhydride Asthma I i Asthma, derma titis ! As thma i i Asthma, urticaria l Asthma, rhinitis McConnell et_ al., 1973 Pepys j2t_ al. , 1976 Baur et al., 1979 Kammermeyer and Mathews, 1973 Koszewski and Hub bard, 1956; Mathews, 1968: Morris, 1960 Kern, 1939; Maccia et a^., 1976 2 425 794961 0076 54 Table I. (cont'd.) Industrial Compound Symptoms Reference .Platinum salts i Asthma, dermatitis Freedman and Krupey, 1968; Cleare et al., 1976 Sodium bichromate Asthma Kobayashi, 1974 .Spiramycin ! i [Tannic acid i Asthma, dermatitis i _ Asthma, urticaria, rhinitis Davies and Pepys, 1975 Johnston et al., 1951 Tetracycline Asthma Menon and Das, 1977 Toluene diisocyanate Asthma, urticaria (TDI) i Avery et al.*, 1969; Pepyst al., 1972 ; Karol ea^., 1979b Trimellitic anhyd ride As thma Zeiss e_t al., 1977 426 794961 0077 Etiologic Agents in Hypersensitivity Pneumonitis Disease Farmer's lung Bagassosis Mushroom picker's disease Humidifier, air-conditioner or heating system disease Fog fever (cattle) Maple bark stripper's disease Sequoiosis Suberosis Paper mill worker's disease Pulpwood handler's disease Brewer's or malt worker's lung Cheese washer's lung Paprika slicer's disease Wheat thresher's iung or grain measurer's lung Pigeon breeder's disease Budgerigar fancier's disease Chicken handler's or feather plucker > disease Turkey handler's disease Pituitary snuff disease Smallpox handler's lung Thatched roof disease (Papuan or New Guinea iung) Tobacco grower's disease joiner's disease Tea grower's disease Bible printer's disease Coptic or mummy disease Detergent disease (asthmalike symptoms--true pneumonitis not identified) Furrier's lung Coffee worker's lung Doghouse disease Lycoperdunosis Exposure Moldy hay or grain Stored sugar cane fiber (bagasse) Moldy vegetable compost Contaminated forced air system Moldy hay Maple tree logs or bark Redwood sawdust Moldy cork dust Moldy wood pulp Moldy wood pulp Malt or barley dust Cheese mold Moldy paprika pods Wheat flour containing weevils Pigeon serum and droppings Contact with parakeets Contact with chickens Contact with turkeys Porcine. bovine pituitary gland (Pitressin snuff) Smallpox scabs Dried grass and leaves Tobacco plants Sawdust lea plants Moldy typesetting water Cloth wrappings of mummies Enzyme detergents Antigen Micropolyspora iacni. Thermoactinomyces vulgaris T saccharii and possibly other organisms M. faeni, T. vulgaris Thermophilic actinomycetes and other organisms Same as farmer's lung OyptDStroma corticate Craphium, Pullularia, Aureobasidium pullulans and other fungi Penicillium species Altemaria Same as above Aspergillus clavatus. A. iumigatus P. casei Mucor stoloniter Sitopbilus granarius Avian proteins Parakeet proteins Chicken proteins Turkey proteins Porcine, bovine proteins Unknown Unknown Unknown Unknown Unknown Unknown Unknown Bacillus subtilii Animal hairs Coffee beans Moldy straw Puffball >pores tivcnpcnh^ pxnhvrv ( ... . water Unknown Coffee bean dust AspergiV/us \ersicnlo' Unknown 55 4 -TOXICOLOGIST'S DISEASE -NOT official: / n / tin i j'n i i t'f : i,, \ i < i' \i r ~ AN I N <\L ROOM CLEANING 427 PROTEINS FROM ANIMALS URINE OR DANDER 794961 0073 F. TISSUE REACTIONS 1) CHRONIC BRON CHITIS (SOURCE: CIBA COLLECTION, VOL.7) 428 Airways cartially or completely Socked or "one-way ` vaive effect by mucoid or muco purulent secretions, with impaired or nonuniform distribution of ventilation 1 'c C.SA 2 . CENTRILOBULAR EMPHYSEMA: SOURCE, CI BA COLLECTION, VOLUME 7. 57 C^rsti ir.cin.-r (Centrilobular) Emphysema Magnified section. Distended, inter communicating, saclike spaces in central area of acini Microscopic section. Distention of airspaces with rupture of alveolar walls Gross specimen. Involvement tends to be most marked in upper part of lung 429 c CIBA 794961 0080 3. ASTHMA: SOURCE, CI BA COLLECTION, VOLUME 7 58 Pathology of Status Asthmaticus > \ ,/ ?* -i..V-5 : if: Tenacious, viscid mucous plugs in airways Mucous plug Polymorphonuclear . neutrophils & (Yli'/ I' Eosinophils - Charcot-Leyden crystals------------- Curschmann's spirals-------------- Cluster of epithelial cells (creola body)- Bacteria and/or viruses J. V V '~\v ^ Qr/J': I % ' Mr - - -1* .J '?! --*--` :>* -V K> * V^c- Epithelial denudation Hyaline thickening of basement membrane Hypertrophy of smooth muscle, mucous glands, and goblet cells Intlammatory exudate with eosinophils and edema Engorged blood vessels J2-0 794961 0081 4 OXIDANT INJURY: SOURCE CIBA COLLECTION, VOLUME 7 Pulmonary Defenses Against Oxidant and Other Noxious Injuries Inhaled High O2 Ozone (O3) NOj Bloodborne Busulfan Thiourea 59 431 794961 0082 COLLECTION, VOLUME 7 pulmonary edema: source, CI8A 60 432 794961 0083 G. SPECIFIC OCCUPATIONAL PULMONARY DISEASE SOURCE, CIBA CLINICAL SYMPOSIUM, VOLUME 30, L978 1. CADMIUM AND BERYLLIUM Plate 2 61 Chronic Beryllium Disease - * z e -\ - ; ^* $ Diffuse emphysema with consolidation at base possibly attributable to chronic cadmium inhalation -- Cf ( D * ... v** *.v ; '9 a ^ ` U* i i .Si j'j- ?* V *. . ' <. -. ; - * *. *. t *. . . * -.` j . ,* " ..-r V ti ' I ' ,* '* I . . * * ^ o 1 * %* ' ' * * ^ % * v91 v of giant cells containing Schaumann bodies Granuloma with interstitial fibrosis resembling sarcoidosis: central deposition of endotheJioid cells. some multinucteated. with surrounding cuff of lymphocytes and fibrous tissue. Skin and other tissues may show similar lesions 433 794961 0084 2. SILICOSIS 62 Plate 5 <-3 Complicated silicosis: massive fibrosis and conglomerate nodulation. Pleura thickened, nodulated, and adhesive VOLUME 30, NUMBER 4 Complicated silicosis: extensive (ibrotic opacification with hyperlucency at bases 11 434 794861 0085 3 . SILICOTUBERCULOS I S Plate 7 63 Tuberculosis with cavitation superimposed on silicosis Rheumatoid Pneumoconiosis (Caplan's Syndrome) CIBA Section through margin of Caplan's nodule: (A) necrotic central area, (B) clefts, (C) zone of fibroblasts and inflammatory cells, (0) collagen VOLUME 30, NUMBER 4 435 Caplan's nodules of various sizes, silicotic nodules, and deposits of coal dust in lung Caplan's nodules in both lungs, with some evidence of dilluse fibrosis 15 794961 0086 ASBESTOSIS Plate 8 64 </' /i'vyvy o*v.-f;-r tr pulmonary asbestosis Moderately advanced asbestosis with extensive fibrosis and distorted alveoli. Asbestos bodies (some fragmented) and a few asbestos fibers in airspaces and interstitium VOLUME 30, NUMBER 4 436 Asbestos bodies in sputum 17 794961 0087 5. COAL WORKER'S PNEUMOCONIOSIS Plate 9 Coal Worker's Pneumoconiosis Thin section of whole lung showing massive black deposits, smaller nodules, necrotic areas, and emphysematous changes Microscopic section through a coal macule demonstrating large amounts of coal dust, both intracellular and extracellular, with fibrosis near artery dIF ' m CIBA i j Chest x-ray film of retired coal miner showing massive upper lobe lesions (sometimes called "angel wings") and nodular disease 18 CLINICAL SYMPOSIA 437 794961 0088 6, KAOLIN' S PNEUMOCONIOSIS Other Mineral Pneumoconioses 66 Plate 10 Kaolin pneumoconiosis transverse cross lung showing whorled masses and smaller that are less hard than silicotic nodules. Microscopic section shows kaolin particles within phagocytes, which are densely packed in alveoli and lying between collagen and reticulin libers in thickened stroma K. f< fc A. <mh Fuller's earth pneumoconiosis: masses of brown pigment within macrophages, chiefly perivascular. Scant tissue reaction VOLUME 30, NUMBER 4 Graphite pneumoconiosis: black deposits and extensive fibrosis. High-power inset shows graphite in alveolar macrophages 21 438 794961 0089 7. PULMONARY SIDEROSIS 67 Platell Reactions to Metals and Mixed Dusts * m&sse mm. t wkf f i* Mixed-dust fibrosis: fibrosis surrounding deposits of iron oxide, carbon, and silica. Found in sandblasters, steel dressers, oxyacetylene cutters, and welders having long-term exposure to mixed dusts Pulmonary siderosis: iron dust inhalation produces little change in lungs other than brick-red coloration, unless iron is mixed with other dusts, chiefly silica, silicates, and/or carbon. The mild fibrosis. ii Tungsten inhalation effects: cellular infiltration and increased collagen in lung interstitium. Alveoli show epithelial metaplasia and contain cellular exudate with some multinucleated cells Nickel inhalation effects: squamous cell carcinoma with overlying metaplastic bronchial mucosa believed attributable this metal r i i 439 . CUNICAI SIMTOStA 794961 0090 68 l 11i \l i i i i 794961 0091 2. HUMAN CARCINOGENS55 69 NOTICE OF INTENDED CHANGES MINERAL DUSTS Substance t Asbestos Amosite...................... Chrysotile.................... Crocidolite................... Tremolite.................... Other forms................ Diatomaceous earth, natural........................ Silica, amorphous......... t Talc (fibrous)................... TLV 0.5 (iber/cc, Ala 2 fibers/cc, Ala 0.2 fiber/cc, A1 a 0.5 fiber/cc, Ala 2 fibers/cc, Ala 1.5 mg/m3, Respirable dust 5 mg/m3, Total dust (all sampled sizes) 2 mg/m3. Respirable dust (< 5/un) 0.5 fiber/cc APPENDIX A CARCINOGENS The Committee lists below those substances in in dustrial use that have proven carcinogenic in man, or have induced cancer in animals under appropriate exper imental conditions. Present listing of those substances carcinogenic for man takes three forms: Those for which a TLV has been assigned (la), those for which environ mental conditions have not been sufficiently defined to assign a TLV (1b), and (1c), those whose reassignment of a TLV is awaiting more definitive data, and hence should be treated as a 1b carcinogen. Ala. Human Carcinogens. Substances, or substances associated with industrial processes, recognized to have carcinogenic or cocarcinogenic potential, with an assigned TLV: TLV " Arsenic trioxide production (AsaOa, 0.05 mg/m3 as As) (SOi. C 5.0 ppm) "See Notice ol Intaided Changes 1978 Addition. 36 Asbestos, all forms* is (Chloromethyl) ether Chromite ore processing (chromate) Nickel sulfide roasting. fume dust Particulate Polycyclic Aromatic Hydrocarbons (PPAH) Vinyl Chloride (SbxQs, 0.5 mg/m3 (as Sb)) (5 fibers/cc. > 5 #im in length) 0.00.1 ppm 0.05 mg/m3 (as Cr) 1.0 mg/m3 (as Ni) 0.2 mg/m3, as benzene solubles 5 ppm Alb. Human Carcinogens. Substances, or substances associated with industrial processes, recognized to have carcinogenic potential without an assigned TLV: Chloromethyl methyl ether 4-Aminodiphenyl (p-Xenylamine) Benzidine production beta-Naphthylamine 4-Nitrodiphenyl Ale. Human Carcinogens. Substances with recognized carcinogenic potential awaiting reassignment of TLV pending further data acquisition: Acrylonitrile 1, 2-Dibromoethane (Ethylene dibromide) For the substances in 1b or 1c, no exposure or contact by any route--respiratory, skin or oral, as detected by the most sensitive methods -- shall be permitted. "No exposure or contact" means hermifemg the process or operation by the best practicable engi neering methods. The worker should be propefly equipped to insure virtually no contact with the . carcinogen. "CigareBe smoking on enhance the incidence ol respiratory caners Iretn this and others of these substances or processes. 37* !i! i;,` :i II ;i *From: American. Conference of J3overnmenta 1 Industrial Hygienists: P.0. Box 197.3, Cincinnati, Ohio 441 794961 0092 70 A2. Industrial Substances Suspect of Carcinogenic Po tential for MAN. Chemical substances or sub stances associated with industrial processes, which are suspect of inducing cancer, based on either (1) limited epidemiologic evidence, exclusive of clinical reports of single cases, or (2) demon i; stration of carcinogenesis in one or more animal species by appropriate methods. 3-Amino 1, 2, 4-triazole ri;!i '* Antimony trioxide production* (0.5 mg/m3) ! Benzene 10 ppm Benz(a)pyrene -- Beryllium 2.0/tg/m3 '* Cadmium oxide production (0.05 mg/m3) Chloroform 10 ppm Chromates of lead and zinc (as Cr) 0.05 mg/m3 3, 3'-Dichlorobenzidine -- Dimethylcarbamyl chloride -- 1,1-Dimethyl hydrazine . 0.5 ppm Dimethyl sulfate -- Skin 0.1 ppm Epichlorhydrin 5 ppm Kexachlorobutadiene -- Hexamethyl phosphoramide -- Skin Hydrazine 0.1 ppm Lead chromate 0.05 mg/m3 4. 4'-Methylene bis (2-chloroaniline) -- Skin 0.02 ppm Monomethyl hydrazine 0.2 ppm C2-Nitropropane 25 ppm Nitrosamines -- Phenyl-beta-naphthylamine -- Propane sultone -- beta-Propiolactone -- Vinyl cyclohexene dioxide 10 ppm Zinc chromate (as Cr) 0.05 mg/m3 For the above, worker exposure by all routes should be carefully controlled to levels consistent with the animal and human experience data (see Documentation), including those substances with a listed TLV. I; Cigarene smoking can enhance the incidence of respiratory cancers from this or others of these substances or processes. 38 A3. Guidelines for the Classification of Experimental ANIMAL Carcinogens. The following guidelines are offered in the present state of knowledge as an aid in classifying substances in the occupational envi ronment found to be carcinogenic in experimental animals. A need was felt by the Threshold Limits Committee for such a classification in order to take the first step in developing an appropriate TLV for occupational exposure. Determination of Approximate Threshold of Re sponse Requirement. In order to determine in which category to classify an experimental carcin ogen for the purpose of assigning an industrial air limit (TLV), an approximate threshold of neoplastic response must be determined. Because of practi cal experimental difficulties, a precisely defined threshold cannot be attained. For the purposes of standard-setting, this is of little moment, as an ap propriate risk, or safety, factor can be applied to the approximate threshold, the magnitude of which is dependent on the degree of potency of the car cinogenic response. To obtain the best 'practical' threshold of neoplas tic response, dosage decrements should be less than logarithmic. This becomes particularly impor tant at levels greater than 10 ppm (or correspond' ing mg/m3). Accordingly, after a range-finding de termination has been made by logarithmic decreases, two additional dosage levels are re quired within the levels of "effect" and "no effect" to approximate the true threshold of neoplastic re sponse. The second step should attempt to establish a me tabolic relationship between animal and man for the particular substance found carcinogenic in an imals. If the metabolic pathways are found compa rable, the substance should be classed highly sus pect as a carcinogen for man. If no such relation is found, the substance should remain listed as an experimental animal carcinogen until evidence to the contrary is found. Proposed Classification of Experimental Animal Carcinogens. Substances occurring in the occupa tional environment found carcinogenic for animals 39 442 794961 0093 71 may be grouped into three classes, those of high, intermediate and low potency. In evaluating the in cidence of animal cancers, significant incidence of cancer is defined as a neoplastic response which represents, in the judgment of the Committee, a significant excess of cancers above that occurring in negative controls. EXCEPTIONS: No substance is to be considered an occupational carcinogen of any practical signifi cance which reacts by the respiratory route at or above 1000 mg/m3 for the mouse, 2000 mg/m3 for the rat; by the dermal route, at or above 1500 mg/kg for the mouse, 3000 mg/kg for the rat; by the gastrointestinal route at or above 500 mg/kg/d for a lifetime, equivalent to about 100 g T.D. for the rat, lOg T.D. for the mouse. These dosage limitations exclude such substances as dioxane and trichlorethylene from consideration as carcinogens. Examples: Dioxane -- rats, hepatocellular and nasal tumors from 1015 mg/kg/d, oral Trichloroethylene--female mice, tumors (30/98 @ 900 mg/kg/d), .oral A3a. INDUSTRIAL SUBSTANCES OF HIGH CARCINO GENIC POTENCY IN EXPERIMENTAL ANIMALS 1. A substance to qualify as a carcinogen of high potency must fulfill one of the three following conditions in two animal species: la. Respiratory. Elicit cancer from (1) dosages below 1 mg/m3 (or equivalent ppm) via the respiratory tract in 6~ 7-hour daily repeated inhalation exposures throughout lifetime; or (2) from a single intratracheally admin istered dose not exceeding 1 mg of parti culate, or liquid, per 100 ml or less of an imal minute respiratory volume; Examples: bis-Chloromethyl ether, malign ant tumors, rats, @ 0.47 mg/m3 (0.1 ppm) in 2 years; 40 Hexamethyl phosphoramide, nasal squamous cell carcir.ox ma. rats, @ 0.05 ppm, in 13 months OR lb. Dermal. Elicit cancer within 20 weeks by skin-painting, twice weekly at 2 mg/kg body weight or less per application for a total dose equal to or less than 1.5 mg. in a biologically inert vehicle; Examples: 7, 12-Dimethy!benz(a)anthracene -- skin tumors @ 0.120.8 mg T.D. in four weeks Bsnz(a)pyrene, mice 12 ftg. 3X/wk tor 18 mos. T.D. 2.6 mg. S0.9% skin tumors OR lc. Gastrointestinal. Elicit cancer by daSy intake via the gastrointestinal tract, within six months, with a six-month holding period, at a dosage below 1 mg/kg body weight per day; total dose, rat, = 50 mg; mouse, ^ 3.5 mg; Examples: 7, 12-Dimethylbenz(a)anihracene -- mammary tumors from 10 mg IX 3-Methylcholanthrene -- Tumors @ 3 sites from 8 mg in 89 weeks Benz(a)pyrene, mice, 3.5% leukemias, from 30 mg T.D. 198 days 2. Elicit cancer by all three routes in at feast two animal species at dose levels prescribed for high or intermediate potency. A3b. INDUSTRIAL SUBSTANCES OF INTERMEDIATE CARCINOGENIC POTENCY IN EXPERIMENTAL ANIMALS To qualify as a carcinogen of intermediate potency, a substance should elicit cancer in two animal spa- 41' .3 : 5 :.j -] j ;i i j, 1 J < :!1 ' < j i s ! i 443 794961 0094 72 .... a.. cies at dosages intermediate between those de scribed in A3a and A3c by two routes of adminis tration. Example: Carbamic acid ethyl ester Dermal, mammary tumors, mice, ' 100%. 63 weeks, 500-1400 mg T.D. Gastrointestinal, various type tumors, mice 42 weeks, 320 mg T.D. Gastrointestinal, various type tumors, rats, 60 weeks, 110-930 mg T.D. A3c. INDUSTRIAL SUBSTANCES OF LOW CARCINO GENIC POTENCY IN EXPERIMENTAL ANIMALS To qualify as a carcinogen of low potency, a sub stance should elicit cancer in one animal species by any one of three routes of administration at the following prescribed dosages and conditions: la. Respiratory. Elicit cancer from (1) dosages greater than 10 mg/m1 (or equivalent ppm) via the respiratory tract in 6- 7-hour, daily re peated inhalation exposures, for 12 months' exposure and 12 months' observation period; or (2) from intratracheally administered dos ages totaling more than 10 mg of particulate or liquid per 100 ml or more of animal minute respiratory volume; Examples: Beryl (beryllium aluminum silicate) malig. lung tumors, rats, @ 15 mg/m1 @ 17 months Benzidine, var. tumors, rats, ` 10-20 mg/m1 @ > 13 mos. OR lb. Dermal. Elicit cancer by skin-painting of mice in twice weekly dosages of > 10 mg/kg body weight in a biologically inert vehicle for at least 75 weeks, i.e., 1.5g T.D. . Examples: Shale tar, mouse, 0.1 ml x 50 -- g T.D. 59/50 skin tumors Arsenic trioxide, man, dose un known, but estimated to be high lc. Gastrointestinal. Elicit cancer from daily oral 42 dosages of 50 mg/kg/day or greater during the lifetime of the animal. APPENDIX B SUSSTANCES OF VARIABLE COMPOSITION B1 Polytetralluoroethylene* decomposition products. Thermal decomposition of the fluorocarbon chain in air leads to the formation of oxidized products con taining carbon, fluorine' and oxygen. Because these products decompose in part by hydrolysis in alkaline solution, they can be quantitatively determined in air as fluoride to provide an index of exposure. No TLV is recommended pending determination of the toxi city of the products, but air concentrations should be minimal. B2 Gasoline. The composition of gasoline varies greatly and thus a single TLV for all types of these materials is no longer applicable. In general, the aromatic hy drocarbon content will determine what TLV applies. Consequently the content of benzene, other aromat ics and additives should be determined to arrive at the appropriate TLV (Elkins, et at. A.I.H.A.J. 24:99, 1953); Runion, ibid. JS. 338,1975). B3 Welding Fumes --Total Particulate (NOCj" TLV. 5mg/m1 Welding fumes cannot be classified simply. The com position and quantity of both are dependent on the alloy being welded and the process and electrodes used. Reli able analysis of fumes cannot be made without consider ing the nature of the welding process and system being examined; reactive metals and alloys such as aluminum and titanium are arc-welded in a protective, inert atmo sphere such as argon! These arcs create relatively little fume, but an intense radiation which can produce ozone. Similar processes are used to arc-weld steels, also creating a relatively low level of fumes. Ferrous alleys also are arc-welded in oxidizing environments, which generate considerable fume, and can produce carbon monoxide instead of ozone. Such fumes generally are composed of discreet particles of amorphous slags con- Trade Names: Aljjoflon. Fluon, Halcn. Teflon. Tetran. ""Hot otherwise classified (NOC). 43 444 794961 0095 MESOTHELIOMA Mesothelioma of Pleura Neoplastic growth associated with asbestosis encasing right lung, infiltrating interlobar fissure, and invading parietal pleura and pericardium. Hemorrhagic fluid In remainder of pleural cavity 73 Fibrosarcomatous type of tumor VOLUME 30, NUMBER 4 Epithelial cell type of lumor Mottled shadow over right lung, with effusion. 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X LU i __1 >LU O LU C -----c cn+-> X-- *-- CD E E -rLU 4-> id JZ 3 4-* O 3 +-> a oo CJ o 4-* X 4-c CJ CJ CJ 4-JZ O +J to o r-- Z CJ >3 CJ.-- *-- 3 O X- JZ o to---- CO to to*--4 CJ CJ U Cs 3 C/7 E ox- CL.GJ id XP CJ CJ CJ X- 3 id +> tz C O fJO-r 4-> t-- JZ dp a r~ O id r--*r- X03 CD o. to o V- CJ CJ X- CD JZ 3 t-T O S-- *-- O *-- 4-- to id t-- CJ O O X-- *r- CJ CL+4 CL *r- tO >!<-- o o id JZ CL *- c = id #-- c o r-- +-> O CJ L> O X. a. r-- id 4- C CJ E c: o >, S- o -r- C > CJ C CD LU < -----tn O' < +-> -- r-- 3 id z 3O 03 C Z Id r- 4-> < CO 74 CO a_ id 4C~> 3 <ac O >> JZ to 3 Xte3cid to CO 3 c<(OD CO OU to id 3+CJJ d c CD too 3 <cD CJ JZ C>J 3c <d 3 JZ o cl --E <o S C_> x3. >o o *- JZ CD CO >c> tCoJ id -- X- o to 4- Hj *3 l-- a JZ CO 0*3 O -s-- CO r-- r- O _+3Q> h- t3o Jt -c cr> CD CD CM CM I r-. o CM rd C S_ 3 O 3 zc c o S- Uu 794961 0097 ifr Copyright 1978 by American Conference of Govern mental Industrial Hygienists. The American Conference of Governmental Industrial Hygienists will welcome requests for permission to re publish or reprint these Threshold limit Values. Re quests for such permission should be directed to the Executive Secretary, P.O. Box 1937, Cincinnati, Ohio 45201. PRICE EACH 1-49................................................................SI .50 50-199............................................................. 1.25 200-999........................................................... 1.10 1000-4999............................................................ 75 5000 or more.........................................................65 Documentation of the Threshold limit Values for Sub stances in Workroom Air. A separate companion piece to the Chemical TLVs is issued by ACGIH under this title. This publication gives the pertinent scientific information and data with reference to literature sources that were used to base each limit. Each documentation also con tains a statement defining the type of response against which the limit is safeguarding the worker. For a better understanding of the TLVs it is essential that the Docu mentation be consulted when the TLVs are being used. Information concerning the availability of copies of the Documentation of the Threshold Limit Values for Substances in Workroom Air should be directed to the Executive Secretary, ACGIH (third edition, fourth print ing. 1978, $20.00). TLVs Threshold Limit Values for Chemical Substances in Workroom Air Adopted by ACGIH for1978 sw 794961 0098 Asbestos Management Plan Review Asbestos Surveys Sampling & Testing Abatement Design common material used in many commercial, residential. A institutional and industrial facilities built before the late 1970s, asbestos is often found in the form of fireproofing. HVAC insulation, decorative plaster, pipe/boiler insulation, ceiling and floor tiles, and various wallboards. Asbestos has been determined to be a potential health hazard, and many states now have regulations restricting asbestos use and requiring inspections of all structures that are being renovated or demolished to determine the presence of asbestos and ensure that adequate abatement measures are taken. Main government agencies are now completing surveys of publiclv owned buildings; and most banks, financial and investment institutions, and insurance companies require similar inspections prior to property transactions. As a service to our clients. Dewberry & Davis has adopted a technically sound, rational engineering approach to asbestos problems. While the presence of asbestos is cause for reasoned concern, it is not generally cause for panic. In many cases, it is but another technical issue to be addressed and managed in the engineering design, renovation, or operation of a building. Our building systems engineering expertise; appreciation of the complex dynamics and economics of building development, ownership, and management; and years of experience in asbestos management services enable us to provide compre hensive, cost-effective solutions to our clients' needs in this critical area. Our services include: Plan and document review to determine the probable locations and quantities ofasbestos that may be present Inspections and surveys to verify existing conditions Sampling and testing programs to define the type, condition, and quantity of asbestos material Preparation ofasbestos management plans, abatement strategies, and abatement cost estimates based on site characteristics and testing results Design of abatement plans and specifications to remove, enclose, or encapsulate asbestos to reduce potential hazards Abatement contract monitoring and construction management fl Dewberry & Davis 794961 0099 Hazardous Waste Management Site Hislor\ Review Waste Characterization ublic concern about environmental damage caused In Phazardous wastes continues to grow. Many wastes, including solvents, heavy metals, asbestos, industrial chemicals, radioactive materials, pesticides, herbicides, and waste oil. are commonplace; yet, disposal and clean-up can be complicated and pose a significant operating, economic, and liability concern to facility owners and managers. In addition, the number and complexity of environmental laws facing developers, builders, and facility owners and operators are increasing, as is public awareness of potential environmental problems and demands for proper handling and disposal. Dewberry & Davis has a long history of responding professionally to the environmental and industrial waste treatment concerns of our clients. Our experience in site development engineering, industrial waste treatment management, and hazard remediation; our EPA-certified laboratory operations; and traditional skills in mapping and ground control provide a unique capability to assist clients in analyzing hazardous waste problems and developing controlled, safe, and economical management programs. Our services include: Record reviews to determine probable locations and quantities of wastes Sampling and testing procedures to identify, map, and measure wastes IFaste management plans, designs, and estimates Contract plans and specificationsfor clean-up or remediation action Clean-up or remediation contract monitoring and management Remediation Design Dewberry & Davis 794961 0100 'I Conrad A. Carter, Jr., P.E. Manager - Environmental Protection Aluminum Company of America Badin. North Carolina 26009 (704) 422-3621 "l Q ALCOA 0X>Wp\. p 794960 0161 4 V HIGH RISK OCCUPATIONAL DISEASE NOTIFICATION AND PREVENTION ACT OF 1987 (H.R. 162 & S.79) I. REQUIREMENTS II. IMPACT ON ALCOA III. COSTS TO ALCOA IV. POSITION ON BILL / STATUS 794960 0162 I. requirements - Identification, Notification, and Prevention of Occupational Disease A. Identification 1. Risk Chemicals a. Occupational Health Hazard b. List Undefined c. Exposure, Duration * d. OSHA Substances (e.g.. Carcinogens) 2. Risk Assessment Board (9) a. HHS (NIOSH) b. 4 Government; 4 non-Government c. Political 3. Rule-making Process a. Public Comment b. Hearing c. Variance Procedures 794960 0163 RISK CHEMICALS A. Dioxin, AIDS - Legislated B. Anticipated Risk Chemicals (36 substances) Hazardous Substance Workers Exposed Asbestos Coal tar pitch volatiles 4-nitrobiphenyl Alpha-napnthylamine 4,4-methylenebis Methyl chloromethyl ether 3,3-dichlorobenzidine Bischloromethyl ether Beta-naphthylamine Benzidine 4-aminodiphenyl Ethyleneimine Beta-propiolactone 2-acetylamino-fluorene 4-bimethyaminoazo-benzene N-nitrosodime-thylamine Inorganic arsenic Lead Coke oven emissions Cotton dust l,2-dibromo-3-chloro-propane Acrylonitrile Ethylene oxide Vinyl chloride Carbon monoxide Benzene Beryllium Cadmium Chloroprene Talc Fibrous glass Methyl butyl ketone Polychlorinated biphenyls Radon daughters Silica, silica flour Formaldehyde 4.000.000 78,764 NA 2,132 2,094 NA 879 11,400 5,816 1,650 NA 1,712 38 896 4,453 7,815 660,000 800,000 59.000 559,700 3,231 55,698 107,450 29,836 1,997,559 2.000.000 30.000 1.500.000 43,712 527,523 200,000 220,000 12.000 23,000 4,993,655 1.600.000 Total Workers Exposed 19,537,013 R.R. Nathan, Associates, Inc. 794960 0164 I. REQUIREMENTS (cont) B. Notification 1. Conducted by NIOSH 2. Current Employees at "Risk" 3. Retroactive Employees at Risk (30 years) 4. Contents of Notification a. Hazard b. Disease c. Latency d. Counseling on Medical Surveillance e. Plant Postings 794960 0165 I. REQUIREMENTS (cont) C. Prevention 1. Medical Monitoring and Counseling a. Current Employees - Employer Cost b. Retroactive - Employee Cost 2. Medical Transfer / Removal Protection a. Same Salary b. 1-Year Severance Pay 3. Occupational Health Centers (10 --> 50) a. Training, Research b. Medical Monitoring, if needed 794960 0166 II. IMPACT ON ALCOA A. Scope Unknown .1 No Defined List 2. Occupational Health Hazard 3. Political Projected Risks (1st 5 Years) .1 Asbestos 2. Coal Tar Pitch Volatiles 3. Silica (Crystalline) 4. Man-made Mineral Fibers 5. PCB's 794960 0167 III. COSTS TO ALCOA A. Costs Unknown B. R. R. Nathan Associates 1. Employer's Total Cost -- = $6 billion per year a. 475,000 workers identified b. 80% notified c. 64% responded d. 3% job removal ($25,000 per employee) e. Medical surveillance ($250 per person) f. 25% file liability ($95,000 per claim) 2. Cost per Notified Employee -- $12,500 a. Direct (2% -- 10%) 1. Medical monitoring 2. Medical removal b. Indirect (90% -- 98%) 1. Litigation expenses 2. Compensation costs 794960 0168 III. Costs to Alcoa (Cont) C. Estimated Alcoa Costs 1. Current Employees -- $54 million a. 5 Substances covered b. 20% Current employees notified 1. HMS exposures 2. One or more exposures 2. Additional Costs a. Retroactive employees (1:1) b. Job rotation 794960 0169 IV. POSITION ON BILL A. Support Medical Concepts 1. Causal Relationships 2. Prudent Medical Surveillance B. Oppose Implementation * 1. Unmeasurable Liability 2. Medical Removal / Job Retention Provisions C. Status 1. Filibustered successfully 2. Return next session j\occupdis.tsp 794960 0170 5 1^ 794960 0171