Document am0K5N7VRG7aN1wzm69eZJBy

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 1 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 ofthe 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 of the 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 of this 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 f 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. 1 CMA 114065 FIGURE 1: FLOWCHART FOR CONSIDERATION OF AGENTS UNDER PROPOSITION 65 4/7/95 OEHHA REVIEWS OATA AND CONDUCTS PRIORITIZATION: OEHHA PREPARES SUPPORTING O'(tCUMENTATION ON ALL AGENTS AND SYNOPSES ON HIl'<3H PRIORITY AGENTS c 1 PRIORITY LIST PUBLIC MEETING: COMMITTEE REVIBWS ANO DISCUSSES PRIORITY LIST. AND SELECTS AGENTS FROM HIGH PRIORITY CATEGORY FOR CONSIDERATION c 3AGENTS UNDER COMMITTEE CONSIDERATION FOR LISTING 45-DAY PUBLIC NOTICE ISSUED: DATA ( OLLECTED AND ANALYZED BY OEHHA c Jx HAZARD IDENTIFICATION DOCUMENT DOCUMENT RELEASED 60 0>/YS PRIOR TO PUBLIC MEETING; DELIBERATION OF AGENTS IN PUBLIC COMMITTEE MEETING lAGENTS c LISTED i ( AGENTS ^ I NOT LISTED J i ( AGENTS ^ I DEFERRED J ] DEVELOPMENT OF ACTION PLAN CMA 114066 r TRACKING DATABASE TIER I SCREENING BY OEHhI FOR AVAILABILITY OF DATA TO BEGIN PRIORITIZATION t TIER OEHHA REVIEWS DATA AND CONDUCTS PRIORITIZATION: OEHHA PREPARES SUPPORTING D $CUMENTATION ON ALL AGENTS AND SYNOPSES ON HidH PRIORITY AGENTS C 3PRIORITY LIST CMA 114067 DRAFT H60 UAKI I HACKING UA IAOAAC - I ICJt I /MjCJN 1 & 4///B Nam* of Aqont acetazolamide acrylamide acrylonitrile aldrin aminoacetonitrile aminonicotinamide, 6aminopropionitrile. Bammonium perfluorooctanoate aniline aprioiate arsenic (inorganic) arsenous oxide asparaginase, L AY-9944 azacytidine, 5azauridine balagnn benzene benzo(a]pyrene beryllium betamethasone boric add boron bromo-Z-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 chloidane chlorfenvinfos chloroform chlorohydrin chloroprene chromium trioxide chromium VI copper sulfate corticosterone cydizine CMA114068 CAS# 59665 79061 l 107131 309002 540614 329895 151188 3825261 62533 52460 7440382 1327533 9015683 366938 320672 54251 71330433 71432 50328 7440417 378449 10043353 7440428 59143 75274 106990 1 93793 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 - CANDIDATE AGENTS UNDER CONSIDERATION FOR DEVELOPMENTAL AND REPRODUCTIVE TOXICITY EVALUTATION*1* Nam of Ag nt Acrylamide Aldrin 1,3-Butadiene Carbamazepine Carbon tetrachloride Chfordan DOT*3* Ethylene dibromide Formaldehyde Heptachlor Methylene chloride Progesterone 2,4,5-T, butyl ester Trichloroethylene Vinyl chloride CAS# Level of Toxicological Concern*2* Laval of Exposure Concern Prl rtty Status - DART 79061 309002 106990 36507309 56235 57749 50293 106934 50000 76448 75092 57830 High High Medium High Medium High High High Low High Low High Medium Low Medium Low Medium Low Medium Low _________ His!!_________ Low High Low High Medium Medium Medium Medium Medium High Medium Medium Medium Medium Medium*4* 93708 79016 75014 Low Medium Medium Low High Medium Low __________m________ Medium (1) Priority chemicals from Donald, JM, Monserrat, LG, Hooper, K, Book, SA and Chemoff, GF (1992). Prioritizing candidate reproductfve/developmental toxicants for evaluation. Reprod Toxicol 6:99-100. (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 toxIcotoQlc concern Consequently, a "low" or "medium" level of toxicologic concern should not be interpreted to mean that the chemical has little or no potential to caus r productive 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. CMA 114069 4/7/95 Page 1 of 1 DRAFT LO exposure concern; HI/MED toxicity consxm 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 AGENIS acrylamide DDT trichloroethylene DRAFT P65 DART TRACKING DATABASE - TIER I AGENTS Nam* f Agent acetazoiamide acrylamide acrylonitrile aldrin aminoacetonitrile aminonicotinamide, 6* aminopropioniirile, Bammonium perfluorooctanoate aniline apholate arsenic (inorganic) arsenous oxide _as_p_ar_ag_inase, L azacytidine. 5azaundine baiaqnn benzene benzolalpyrene beryllium betamethasone boric acid boron bromo-7*deoxyuridine, 5bromodicriloromethane butadiene, 1,3butyl ester, 2,4,5-T butyl ester. 2.4-0 cadmium cadmium sulfate caffeine cannabis captan carbamazepine cartoon dioxide cartoon tetrachloride cartoutamide chloramphenicol chlordane chlorfenvinfos chloroform chlorohydrin chloroprene chromium tnoxide chromium VI copper sulfate corticosterone cydizine ODE : 4/7/95 i CAS* i 59665 i 79061 ! 107131 ! 309002 1 540614 I 329895 I 151188 3825261 1 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 36507309 124389 56235 339435 56757 57749 470906 67663 96242 126998 1333820 18540299 7758987 50226 82928 72559 Pag* 1 of 4 CMA 114071 ) DRAFT I P65 DART DATABASE - TIER I AGENTS 4/7/95 DDT diaminostiibene dichloroethylene. 1.1* dichioropropane. 1.2* diehlrin diethylene glycol diethyl ether diethytene glycol dimethyl ether diethylene glycol methyl ether diethylhexyt phthalate diltiazem dimethyl acetamide dimethyl-1,2-benz<a)antnracene. 7.12dimpylate dinitrotoluene. 2.6dromostanolone propionate EM 12 endhn enflurane environmental tobacco smoke epichlorohydhn estradiol. 17-beta ethisterone ethosuximide ethoxyethyl acetate. 2ethylene dibromide ethylene glycol diethyl ether ethylene glycol dimethyl ether ethylmtrosourea ethylnylestradiol etizotam fluoroacetate folpet formaldehyde formamide furylfuramide griseofulvin hadacidin halothane heptachlor heroin hexamethylene diisocyanate hexane. Nhydroxy-oxo-L-norvaline hydroxyprogesterone hydroxytryptophan. 5hyroxyurea idoxundine indomethacin insulin (natural) karatnane I 50293 ! 621965 75354 i 75875 60571 112367 > 111966 I 111773 1 117817 142399417 1 127195 1 57976 1 333415 125321146 l 521120 126581817 > 72208 13838169 1 106898 i 50282 l 434037 1 77678 f 111159 1 106934 1 629141 1 110714 i 759739 1 57636 > 40054691 > 144490 133073 50000 75127 1 3688537 1 126078 ! 689134 I 151677 1 76448 1 561273 1 822060 i 110543 ! 4439843 68962 1 56699 1 127071 1 54422 1 53861 1 9004108 ! 39300453 Page 2 of 4 CMA 114072 DRAFT P65 DART TRACKING DATABASE r TIER I AGENTS 4/7/95 manganese 7439965 mestranot 72333 methadone 76993 methandrostenoione 72639 methoxyethyl acetate. 2- 110496 methoxyflurane 76380 methyl 2(p-allophanoyibenzyi)hydrazine. i- 60344 methyl butyl ketone 591786 methyl chloride 74873 methyl PGA, X* i methyl salicylate 119368 methytacetamide. N- 79163 methyiazoxymethanol 590965 methylene bis(4-cyclohexyiisocyanate) 5124301 methylene chloride 75092 methylformamide 123397 methylpyrrolidone. N- 872504 monocrotophos 6923224 monosodium glutamate 142472 myclobutanil 88671890 N-methylnitrosourea (n-nrtroso-n-methylurea) 684935 n-nitroso bis(2-oxopropyl)amme 60599384 nickel caitxmyl 13463393 nitrochlorobenzene, p- 100005 nitrofen 1836755 nitroquinolone-1-oxide, 4- 56575 nitrous oxide 10024972 ochratoxin A 303479 oxydemeton-methyl oxytocin 301122 50566 phencyclidine (PCP) 77101 phenol 108952 phenoxyoenzamtne 59961 phenylalanine <DL) 3617445 prednisolone 50248 primidone 125337 progesterone 57830 propaigite 2312358 propylene glycol methyl ether, beta-isomer (PGME-beta, 2-methoxy-1 -propanol) 1 1589497 pyrimethamine 58140 razoxane 24584098 red palm oil 8002753 Ro 10-9359 54350480 strontium (unspecified salt) 543942 styrene 100425 tetrachloroacetone 31422614 tetrahydrocannabinol (THC) 1972083 thiouracil 141902 thiram 137268 thyroxine 51489 Page 3 of 4 CMA 114073  DRAFT I P65 DART TRACKING DATABASE - TIER I AGENTS 4/7/95 tolbutamide toluene 2.4-diisocyanate toxapnene triamcinolone trichloroethylene trichlorofon tricyanoaminopropene triethylene glycol dimethyl ether trypan blue vinyl chloride vitamin D xylene 64777 584849 8001352 124947 79016 52686 1 112492 72571 75014 1406162 1330207 Page 4 of 4 CMA 114074 PROPOSITION 65 PRIORITY LIST - CANDIDATE AGENTS UNDER CONSIDERATION FOR DEVELOPMENTAL AND REPRODUCTIVE TOXICITY EVALUTATION*1*2 Name of Agent Acrylamide Akfrtn 1,3-Butadiene Carbamazepine Carbon tetrachloride Chlonfane DOT*3*4 Ethylene dibromide Formaldehyde Heptachlor Methylene chloride Progesterone 2,4,5-T, butyl ester Trichloroethylene Vinyl chloride CAS# 79061 309002 106990 36507309 56235 57749 50293 Level of Toxicological C_ oncern(2) High High Medium High Medium High High 106934 50000 76448 75092 57830 High Low High Low High 03798 76016 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^ Low High Medium (1) Priority chemicals from Donald, JM, Monserrat, LG, Hooper, K, Book, SA and Chemofr, GF (1992). Prioritizing candidate reproductive/developmental toxicants lor evaluation. Repmd Toxicol 6:90-108. (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 wilt alter the assigned level of toxicologic concern". Consequently, a low* or "medium" level of toxicologic concern should not be Interpreted to mean that the chemical has Htlle or no potential to cause reproductive or developmental effects. (3) Would also indude consideration of major metabolites and breakdown produds such as DDE (CAS # 72559) and DDD (CAS # 72548). (4) Progesterone is Intentionally used as a contraceptive. Unintentional exposures are believed to be law. 4/7/95 Page 1 of 1 DRAFT CMA114075