<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 />
|