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PROPOSAL FOR PRIORITIZING CANDIDATE AGENTS FOR CONSIDERATION UNDER PROPOSITION 65 BY THE OEHHA SCIENCE ADVISORY BOARD Reproductive and Cancer Hazard Assessment Section Office ofEnvironmental Health Hazard Assessment California Environmental Protection Agency April 7, 1995 X BACKGROUND The Safe Drinking Water and Toxic Enforcement Act (Proposition 65, California Health and Safety Code 25249.5 et seq.) requires the Governor to publish lists of agents known to cause cancer and reproductive toxicity. One of the mechanisms by which an agent is placed on this list is a finding by the "state's qualified experts'* that an agent has been clearly shown through scientifically valid testing according to generally accepted principles to cause cancer or reproductive toxicity. As lead agency for the implementation ofProposition 65, the Office of Environmental Health Hazard Assessment (OEHHA) has formed two committees ofthe Science Advisory Board (SAB) to serve as the state's qualified experts. These committees are the Developmental and Reproductive Toxicant (DART) Identification Committee and the Carcinogen Identification Committee. The purpose ofthis draft document is to propose a mechanism for compiling and prioritizing candidate agents for consideration by the SAB Identification Committees. The proposed mechanism provides a systematic process for compiling and tracking possible candidate agents and for prioritizing these agents for consideration by the Identification Committees. Key elements include (1) a database to track agents suggested for consideration, (2) development by OEHHA of a priority list of agents, grouped into high, medium, or low priority on the basis of their potential for human exposure and developmental/reproductive or carcinogenic hazard, and (3) expert review in the final prioritization of agents. Opportunity is provided for input and review by state agencies and departments, the scientific community, and other interested parties both in the suggestion of candidate agents and the development of the priority lists. As emphasized by California's Court of Appeal (1989), Proposition 65 directs the state "to engage in a diligent, thorough, and continuing search for additional chemicals which evolving scientific knowledge demonstrates are subject to the Act." Accordingly, the meeting agendas of the Identification Committees will largely be taken up by consideration of potential candidates for listing generated by this process. Other items that may compete for space on the agendas include, for example, proposed delistings of particular agents or general scientific issues to be considered in listing. BFG 002173 1 FIGURE 1: FLOWCHART FOR CONSIDERATION OF AGENTS UNDER PROPOSITION 65 4/7/95 OEHHA REVIEWS OATA AND CONDUCTS PRIORITIZATION: OEHHA PREPARES SUPPORTING 0OCUMENTATION ON ALL AGENTS AND SYNOPSES ON HI,<3H PRIORITY AGENTS C PBJORJTY LIST ) PUBLIC MEETING: COMMITTEE REVIE WS AND DISCUSSES PRIORITY LIST. AND SELECTS AGENTS FROM HIGH PRIC RITY CATEGORY FOR CONSIDERATION C 3AGENTS UNDER COMMITTEE CONSIDERATION FOR LISTING 4S-DAY PUBLIC NOTICE ISSUED; DATA < OLLECTED ANO ANALYZED BY OEHHA C HAZARD IDENTIFICATION DOCUMENT DOCUMENT RELEASED 60 D; YS PRIOR TO PUBLIC MEETING; DELIBERATION OF AGENTS l 4 PUBLIC COMMITTEE MEETING r ( AGENTS l LISTED T AGENTS NOT LISTED 1 AGENTS DEFERRED I DEVELOPMENT OF ACTION PLAN BFG 002174 TRACKING DATABASE TIER I SCREENING BY OEHhA FOR AVAILABILITY OF DATA TO BEGIN PRIORITIZATION TIER OEHHA REVIEWS DATA AND CONDUCTS PRIORITIZATION; OEHHA PREPARES SUPPORTING D(J>CUMENTATION ON ALL AGENTS AND SYNOPSES ON Hl<3H PRIORITY AGENTS ____I_____ PRIORITY LIST ) BFG 002175 DRAFT Pttd QAK1 1 KAUKJNO UA I ADAdC * I JfcK 1 iO Name of Agent acetazoiarmde acrylamide acrylonitrile akJrin aminoacetonitrile aminonicotinamide. 6aminopropionrtrile, Bammonium perfluorooctanoate aniline apholate arsenic (inorganic) arsenous oxide asparaginase, L AY-9944 azacytidine, 5azauridine balagnn benzene benzo[a]pyrene beryllium betamethasone boric acid boron bromo-2*-deoxyuridine, 5bromodichloromethane butadiene, 1,3butyl ester, 2.4,5-T butyl ester. 2,4-0 cadmium cadmium sulfate caffeine cannabis captan carbamazepine carbon dioxide carbon tetrachloride carbutamide chloramphenicol chlordane chlorfenvinfos chloroform chlorohydrin chloroprene chromium trioxide chromium VI copper sulfate corticosterone cyclizine ODE BFG 002176 4//#0 CAS# 59665 79061 107131 309002 540614 329895 151188 3825261 62533 52460 7440382 1327533 9015683 366938 320672 54251 71330433 71432 1 50328 7440417 378449 10043353 7440428 59143 75274 106990 93798 94804 7440439 10124364 58082 8063147 133062 36507309 124389 56235 339435 56757 57749 470906 67663 96242 126998 1333820 18540299 7758987 50226 82928 72559 PROPOSITION 65 PRIORITY LIST - CANO \TE AGENTS UNDER CONSIDERATION FOR DEVELOPMENTAL AND REPRODUCTIVE TOXICITY EVALUTATION*1* Name of Agent Acrylamide Aldrin 1,3-Butadiene Carbamazepine Carbon tetrachloride Chlordane DDT(3* Ethylene dibromide Formaldehyde Heptachlor Methylene chloride Progesterone 2,4,5-T, butyl ester Trichloroethylene Vinyl chloride CAS# Level of Toxicological Concern*2*3 79061 309002 106990 36507309 56235 57749 50293 106934 50000 76448 75092 57830 High High Medium High Medium High High High Low High Low High 93798 79016 75014 Low Medium Medium Level of Exposure Concern Medium Low Medium Low Medium Low Medium Low High Low High Low Low High Medium Priority Status - DART High Medium Medium Medium Medium Medium High Medium Medium Medium Medium Medium*4* Low High Medium (1) Priority chemicals from Donald, JM, Monserrat, LG, Hooper, K, Book, SA and Chemoff. GF (1992). Prioritizing candidate reproductive/developmental toxicants for evaluation. Reprod Toxicol 6:99-108. (2) The evaluation of the level of toxicological concern is based on secondary sources (databases and reviews). It is likely that data exist which have r, been considered in the evaluation. In a more detailed review, additional data may be found that will alter the assigned "level of toxicologic concern Consequently, a Tow" or "medium" level of toxicologic concern should not be interpreted to mean that the chemical has little or no potential to caus reproductive or developmental effects. (3) Would also Include consideration of major metabolites and breakdown products such as DDE (CAS # 72559) and DDD (CAS # 72548). (4) Progesterone is intentionally used as a contraceptive. Unintentional exposures are believed to be low. 4/7/95 Page 1 of 1 BFG 002177 DRAFT LO exposure concern; HIJMEDtoxicitv concern aldrin chlordane ethylene dibromide heptachlor 2,4,5-butyl ester progesterone carbamazepine HI exposure concern; LO toxicity concern formaldehyde methylene chloride MED exposure concern; MED toxicity concern 1,3-butadiene carbon tetrachloride vinyl chloride HI PRIORITY AGENTS acrylamide DDT trichloroethylene DRAFT P65 DART TRACKING DATABASE - TIER I AGENTS Name of Agent acetazoiamide acrylamide acrylonitrile aWrin aminoacetonitrile aminonicotinamide. 6aminopropionrtrile, Bammonium perfluorooctanoate aniline aoholate arsenic (inorganic) arsenous oxide asparaginase, L AY-9944 azacytidine, 5azaundine balaqnn benzene benzo(a)pyrene beryllium betamethasone boric acid boron bromo-2'-deoxyuridine, 5bromodichtoromethane butadiene, 1,3butyl ester, 2,4,5-T butyl ester. 2,4-0 cadmium cadmium sulfate caffeine cannabis captan carbamazepine carbon dioxide carbon tetrachloride carbutamide chloramphenicol chlordane chlorfenvinfos chloroform chlorohydrin chloroprene chromium trioxide chromium VI copper sulfate corticosterone cydizine DDE 4/7/95 i CAS# ! 59665 79061 107131 309002 540614 329695 1 151188 1 3825261 i 62533 52460 7440382 1327533 9015683 366938 320672 54251 71330433 71432 50328 7440417 378449 10043353 7440428 59143 75274 106990 93798 94804 7440439 10124364 58082 8063147 133062 136507309 124389 56235 339435 56757 57749 470906 67663 96242 126998 1333820 18540299 7758987 50226 82928 1 72559 Page 1 of 4 BFG 002179 DRAFT P65 DART TRACKING DATABASE - TIER I AGENTS DDT diaminostilbene dichloroetnyiene. 1.1dichloropropane. 1.2dietdrin diethylene qiycol diethyl ether diethylene qtycol dimethyl ether diethylene glycol methyl ether diethylhexyl phthaiate dittiazem dimethyl acetamide dimethyl-1,2-benz(a)anthracene, 7,12dimpyiate dinitrotoluene. 2.6dromostanolone propionate EM 12 endrin enflurane environmental tobacco smoke epichlorohvdrin estradiol. 17-beta ethisterone ethosuximide ethoxyethyl acetate. 2ethylene dibromide ethylene glycol diethyl ether ethylene glycol dimethyl ether ethylnitrosourea ethylnylestradioi etizolam fluoroaceiate folpet formaldehyde formamide furylfuramide griseofuivin hadacidin halothane heptachtor heroin hexamethylene diisocyanate hexane. Nhydroxy-oxo-L-norvaline hydroxyprogesterone hydroxytryptophan. 5hyroxyurea idoxundine indomethacin insulin (natural) karathane 4/7/95 1 50293 > 621965 75354 l 78675 i 60571 i 112367 i 111966 1 111773 1 117817 142399417 1 127195 1 57976 1 333415 125321146 1 521120 126581817 i 72208 13838169 1 106898 1 50282 1 434037 l 77678 ! 111159 I 106934 1 629141 1 110714 1 759739 1 57636 i40054691 144490 133073 50000 75127 1 3688537 1 126078 ! 689134 1 151677 1 76448 1 561273 1 822060 i 110543 ! 4439843 68962 l 56699 1 127071 1 54422 t 53861 | 9004108 1 39300453 Page 2 of 4 BFG 002180 DRAFT P65 DART TRACKING DATABASE - TIER 1 AGENTS 4/7/95 manganese 7439965 mestranol 72333 methadone methandrostenoione 76993 72639 methoxyethyl acetate. 2- 110496 methoxyflurane 76380 methyl 2(p-aliophanoylbenzvl)hydrazine. 1- 60344 methyl butyl ketone 591786 methyl chloride 74873 methyl PGA, X- I methyl salicylate 119368 methyiacetamide, N- 79163 methylazoxymethanol 590965 methylene bis(4-cydohexylisocyanate) 5124301 methylene chloride methylformamide 75092 123397 methylpyrroiidone. N- 872504 monocrotophos 6923224 monosodium glutamate 142472 myciobutanil 88671890 Nmethylnitrosourea (n-nitroso-n-methylurea) 684935 n-nitroso bis(2-oxopropyl)amine 60599384 nickel carbonyl 13463393 nitrochtorobenzene. p- 100005 nitrofen 1836755 nitroquinolone-1-oxide, 4- 56575 nitrous oxide ochratoxin A 10024972 303479 oxydemeton-methyl oxytocin phencyclidine (PCP) 301122 50566 77101 phenol 108952 phenoxybenzamme 59961 phenylalanine <DL) 3617445 prednisolone 50248 primidone 125337 progesterone 57830 propargite 2312358 propylene glycol methyl ether, beta-isomer (PGME-beta, 2-methoxy-l-propanol) 1589497 pyrimethamine 58140 razoxane 24584096 red palm oil Ro 10-9359 8002753 54350480 strontium (unspecified salt) 543942 styrene 100425 tetrachioroacetone [31422614 tetrahydrocannabinol (THC) 1972083 thiouracil 141902 thiram 137268 thyroxine 51469 Page 3 of 4 BFG 002181 DRAFT P65 DART TRACKING DATABASE - TIER I AGENTS tolbutamide toluene 2.4-diisocyanate toxaonene triamcinolone trichloroethylene trichlorofon tricyanoaminopropene triethylene glycol dimethyl ether trypan blue vinyl chloride vitamin D xylene 4/7/95 1 64777 1 564849 i 8001352 1 124947 1 79016 1 52686 1 i 112492 i 72571 | 75014 1 1406162 1 1330207 Page 4 of 4 BFG 002182 PROPOSITION 65 PRIORITY LIST - CANDIDATE AGENTS UNDER CONSIDERATION FOR DEVELOPMENTAL AND REPRODUCTIVE TOXICITY EVALUTATION*1* Name of Agent Acrylamide Aldrin 1,3-Butadiene Carbamazepine Carbon tetrachloride Chlordane ddt(3> Elhylene dibromide Formaldehyde Heptachlor Methylene chloride Progesterone 2.4,5-T, butyl ester Trichloroethylene Vinyl chloride CASH 79061 309002 106990 36507309 56235 57749 50293 106934 50000 76448 75092 57830 93798 79016 75014 Level of Toxicological Concern*2*3 High High Medium High Medium High High High Low High Low High Low Medium Medium Level of Exposure Concern Medium Low Medium Low Medium Low Medium Low High Low High Low Low High Medium Priority Status - DART High Medium Medium Medium Medium Medium High Medium Medium Medium Medium Medium*4* Low High Medium (1) Priority cfteffticdte from Donate, JM. Monserral, LG, Hooper, K, Book, SA and Chemoff, GF (1992). Prioritizing candidate reproductive/developmental toxicants for evaluation. Reprod Toxicol 6:99-108. (2) The evaluation of the level of toxicological concern is based on secondary sources (databases and reviews). It is likely that data exist which have not been considered in the evaluation. In a more detailed review, additional data may be found that will alter the assigned level of toxicologic concern". Consequently, a "low" or "medium" level of toxicologic concern should not be interpreted lo mean that the chemical has little or no potential to cause reproductive or developmental effects. (3) Would also Indude consideration of major metabolites and breakdown products such as DDE (CAS # 72559) and DDD (CAS # 72548). (4) Progesterone is intentionally used as a contraceptive. Unintentional exposures are believed to be low. 4/7/95 Page 1 of 1 BFG 002183 DRAFT