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<br />products io awls, stops, and the eDVi- <br />ronment. <br />The extensive amounts of new re- <br />search on 2,4D provide valuable new per- <br />spectives affirming the minimal potential <br />for the use of 2,4D to adversely affect <br />the enviroDmen[ or human health (9). The <br />futdings of the recent scientific activities <br />supporting this conclusion are briefly <br />cnmmari~rri 1D 11115 paper. <br />'POXICOLOGY <br />Ctu+cinogetvcity <br />The carcinogeoiciry of 2,4D haz been <br />reviewed by Dtunerous scient~c and <br />regulatory groups including dre Environ- <br />mental Protection Agency, Agricultural <br />Canada, the Ontario Ministry of the ED- <br />vironmeDt, the Council on Agricultural <br />Science and Technology, and the Harvard <br />School of Public Health (1,4,6,7,10, <br />12,15,21) (Table 1). The EPA has placed <br />2,4-D is carcinogenicity category "D," <br />pending the submissioD and assessment <br />of the repeat studies (8,10).' The cons®- <br />sus opinion is thaz the weight of the evi- <br />dence does not show a cause and effect <br />relationship between 2,4D and cancer. <br />Animal Sludits: Lifetime studies in <br />laboratory animals completed in 1986 <br />found no evidence of cancer in female rats <br />or in male and female mice tad high doses <br />of 2,4D (l6). Importandy, a finding of a <br />weak azsociatioD between 2,4-D treat- <br />ment and brain tumors (astrocymmas) in <br />male rats has been judged by athird-party <br />cancer expert to be unrelated to herbicide <br />treatmeDt (20). Thus, the weigh[-ofcvi- <br />dence conclusion from the 1986 studies <br />was thaz 2,4D cannot be viewed az caus- <br />ing cancer in animals. <br />EPA testing guidelines require that <br />anima! cancer tests must be conducted az <br />the ma:imam tolerated dose (MT'D), i.e., <br />the Ltrgest daily exposure that causes evi- <br />dence of toxicity to the animals but does <br />Dot cause excessive deaths over the life <br />span of the animals. After an evaluation <br />of the 1986 study, the EPA questioned <br />whether the top dose had attaiDed an MTD <br />dose level. To ensure that the potential <br />'Gregory D is deFmed ss insdequYe date upon <br />which m make an assessmem of peticide <br />aaeogrniciry. <br />~~ <br />TABLE 1. To:kobgkal test summary of 2,4D (acid). <br />z1-Day annul 1000 (NOAa°1 sapMly hnYating <br />7eralobpy, tai 25 not tenstopsnk <br />Tenblopy, /ebhll 30 not rerefepenlC <br />2-Oenaratlm. cal 5 Imp nPmtlueM~e rlek <br />lawesk eubdlronk, rat s NOEL is 1 a mplkpldq kr 2,4D DMA• <br /> NOEL b ZZ mphglday for 2.4D 2-ENE° <br />19-WSek eubtlrronk, mouse 15 - <br />2-Yam ehronle, rat 5 n0 BYNMrea Ot Wrtlnopenk aReas <br />2-Veer dnorrk, moues 5 no evldenee d ®rrJrropsme etfsc7e <br />1-Yser dnorde, dap 1 LOEL' m 5 mplkpMry <br />1-rear Cronk neurotmdcYy. M 5 not neumtmdo <br />Mutagenialy <br />Arras - na mwapeme <br />f]rromosome aberratbn - rot mNaperdc <br />IAsedieduMd DNA SyrMSeie - rotmWapenk <br />'NOEL is the ro obrerved eftea kvd. eEthylhesy! ester of 2,4-D. <br />°NOAEL is the ro ohrenrd adverse effect IeveL •Ordy 2,4-D (acid) was tined in mo¢ce. <br />`Dimerhylamine .colt nf2,4-D. ~/AEZ is the fawert observed effect level. <br />cazcinogenicity of 2,4-D had been az- <br />sessed coder conditioac of MTD dosing, <br />the EPA ~~ that lifetime studies in <br />rats and mice be repeated a[ top dose lev- <br />els from three to six times higher than <br />[base used in the previous research. These <br />new 2-year lifetime tests were conducted <br />az significantly higher doses and were <br />completed in 1995. The results showed <br />no evidence of brain saucer or other types <br />of cancer (16,17). <br />Epidemiology: Retrospective studies <br />of ezposcd populations have yielded <br />iDCOOSisteot results, with some smtiies <br />suggesting a risk of non-Hodgkin's lym- <br />phoma (2,14,35) and others questioning <br />it (5,18,23,28,33). More recently, how- <br />ever, an EPAtonvened panel of roxicol- <br />ogy and epidemiology experts concluded <br />in 1994 (12), after evaluating both the <br />animal and human evidence, that specific <br />associations reported between use of <br />2,4-D in agriculture and appearance of <br />cancer were az most weak and inconsis- <br />tent Significantly, the EPA panel further <br />Doted that possible cancer risks in farm <br />workers could not be attributed specifi- <br />cally to the use of 2,4D when compared <br />to other potential hazards associated with <br />farming as an occupation. Given the lev- <br />els of exposure Cor users, the report con- <br />dudes thaz if 2,4D were to cause cancer, <br />i[ would have m be an extremely pooent <br />carcinogen affecting humans but ia[ ani- <br />mals and acting by a unique mechanism <br />which haz yet m be understood. Addi- <br />tional studies were suggested by the EPA <br />panel az a means of distinguishing these <br />inconsistencies. <br />MutageDieity: 2,4D is considered <br />nonmu[ageoic based on 26 studies of <br />seven derivatives of 2,4D (tecFlsical for- <br />mulations) conducted under current pro- <br />[awls. Although some prior studies have <br />yielded positive results, the previously <br />noted EPA expert panel concluded [hat <br />these older studies have significant ex- <br />perimental deficiencies and thaz "the cnr- <br />rently available evidence suggests that <br />2,4D is noogenotoxtc" (l2). <br />Metabolism: Research in animals <br />and humans has shown that 2,4D has a <br />very short half-life in the body, estimated <br />at between 10 and 36 hours. The com- <br />pound isabsorbed into the body intact and <br />excreted essentially unchanged (not me- <br />tabolized), with nearly all of the 2,4D <br />body burden being cleared within 2 to 4 <br />days in the absence of sustained exposure <br />(19,24,15,29,30). GiveD its rapid clear- <br />ance, 2,4D is not regarded az a pcstiride <br />thaz will accumulate in the body. It is im- <br />