Chronic Dietary Toxicity/Oncogenicity Studies on 2,4-Dichlorophenoxyacetic Acid in Rodents

Charles, Jeffrey M.; Bond, Denise M.; Jeffries, T.K.; Yano, Barry L.; Stott, William T.; Johnson, Keith A.; Cunny, Helen; Wilson, Ronald D.; Bus, James S.

doi:10.1006/faat.1996.0154

Cited by 60 publications

(24 citation statements)

References 16 publications

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“…There are contradictory results in the literature about the toxicity and possible mutagenic effect of the herbicide 2,4-D, but some investigations emphasize on the observed cellular mutations after exposure which can lead to cancer, immunosuppression, reproductive damage and neurotoxicity (Hayes et al, 1991;Amer & Aly, 2001;Charles et al, 1996b;Rosso et al, 2000). Charles et al, (1996a) found no oncogenic effect of 0-300 mg/kg 2,4-D in mice or 0-150 mg/kg in rats, although slightly increase in primary hepatocellular adenomas were observed in female mice, but with lack of dose response. In vivo studies found that 2,4-D included chromatid breaks, chromatid fragments, ring chromosomes, dicentric chromosomes, and chromosome fragments in bone marrow cells in rats (Adhikari & Grover, 1988) and increased rates of sister chromatid exchanges were determined in cultured human lymphocytes (Turkula & Jalal, 1985) if applied at lower dosage.…”

Section: 4-dichlorophenoxyacetic Acid (24-d) (Merck Germany)mentioning

confidence: 71%

Genomic Sensitivity of Small Mammals - A Suitable Test System in the Genetic Monitoring

Topashka-Ancheva¹,

Gerasimova²

2012

Ecotoxicology

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Section: 4-dichlorophenoxyacetic Acid (24-d) (Merck Germany)mentioning

confidence: 71%

Genomic Sensitivity of Small Mammals - A Suitable Test System in the Genetic Monitoring

Topashka-Ancheva¹,

Gerasimova²

2012

Ecotoxicology

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“…Given this non-linear behavior, saturation of 2,4-D renal clearance at 50 mg/kg suggests that animal toxicity findings observed at this dose level and higher overestimate potential human risks. In the case of dogs, both subchronic and chronic studies indicate this species, with an overall NOAEL of 1 mg/kg/day (Charles et al 1996b), is more sensitive to 2,4-Dinduced toxicity than rodents, with an overall NOAEL of 5 mg/kg/ day (Charles et al 1996c). Since the dog is lacking an effective renal organic anion clearance mechanism, this differential species response has been attributed to an inability of the dog to effectively clear 2,4-D from the body, resulting in significantly higher 2,4-D blood concentrations in dog relative to rats and humans at an equivalent oral dose of 5 mg/kg (Van Ravenswaay et al 2003;Timchalk, 2004).…”

Section: Differentiating Potential Endocrine Modes Of Action Based Onmentioning

confidence: 99%

“…US EPA Office of Pesticide Program (OPP) 83-4 guideline two-generation reproductive toxicity study (Rodwell & Brown 1985); OPP 83-3 guideline developmental toxicity study in rats (Rodwell 1983;Charles et al 2001); OPP 83-3 guideline developmental toxicity study in rabbits (Hoberman 1990;Charles et al 2001); OPP 82-1 guideline 13-week rat subchronic toxicity study (Schulze 1991a;Charles et al 1996a) non-guideline 13-week rat subchronic toxicity studies (Gorzinski et al 1981a(Gorzinski et al , 1981b; OPP 83-5 guideline two-year rat chronic toxicity/oncogenicity study (Jeffries et al 1995;Charles et al 1996c);…”

Section: Selection Of Regulatory Mammalian Toxicology Studies For Incmentioning

confidence: 99%

“…OPP 82-1 guideline 13-week mouse subchronic toxicity (Schulze 1991b); OPP 83-2 guideline-equivalent mouse oncogenicity evaluations (Stott 1995a(Stott , 1995bCharles et al 1996c); OPP 82-1 non-guideline 13-week dog subchronic toxicity study (Schulze 1990) OPP 82-1 guideline 13-week dog subchronic toxicity (Dalgard 1993a;Charles et al 1996b); and OPP 83-1 guideline dog chronic toxicity study (Dalgard 1993b;Charles et al 1996b). …”

Section: Selection Of Regulatory Mammalian Toxicology Studies For Incmentioning

confidence: 99%

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Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis

Neal

Marty

Coady

et al. 2017

Critical Reviews in Toxicology

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A comprehensive weight-of-the-evidence evaluation of 2,4-dichlorophenoxyacetic acid (2,4-D) was conducted for potential interactions with the estrogen, androgen and thyroid pathways and with steroidogenesis. This assessment was based on an extensive database of high quality in vitro, in vivo ecotoxicological and in vivo mammalian toxicological studies. Epidemiological studies were also considered. Toxicokinetic data provided the basis for determining rational cutoffs above which exposures were considered irrelevant to humans based on exceeding thresholds for saturation of renal clearance (TSRC); extensive human exposure and biomonitoring data support that these boundaries far exceed human exposures and provide ample margins of exposure. 2,4-D showed no evidence of interacting with the estrogen or androgen pathways. 2,4-D interacts with the thyroid axis in rats through displacement of thyroxine from plasma binding sites only at high doses exceeding the TSRC in mammals. 2,4-D effects on steroidogenesis parameters are likely related to high-dose specific systemic toxicity at doses exceeding the TSRC and are not likely to be endocrine mediated. No studies, including high quality studies in the published literature, predict significant endocrine-related toxicity or functional decrements in any species at environmentally relevant concentrations, or, in mammals, at doses below the TSRC that are relevant for human hazard and risk assessment. Overall, there is no basis for concern regarding potential interactions of 2,4-D with endocrine pathways or axes (estrogen, androgen, steroidogenesis or thyroid), and thus 2,4-D is unlikely to pose a threat from endocrine disruption to wildlife or humans under conditions of real-world exposures.ARTICLE HISTORY

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“…Os efeitos de diferentes níveis de concentração do 2,4-D administrados em doses únicas ou continuados sobre alguns sistemas orgânicos animais, principalmente de cães e ratos, têm sido analisados (HANSEN; QUAIFE; HABER-MANN, 1971;EPA, 1987;KELLY;GUIDOTTI, 1989;TS-MAN, 1991;CHARLES et al, 1996aCHARLES et al, e 1996bPAULINO;GUERRA;PALERMO-NETO, 1996;MATTSSON et al, 1997;GARABRANT;PHILBERT, 2002;AYDIN;ÖZDE-MIR;UZUNÖREN, 2005;BUKOWSKA et al, 2008).…”

Section: Introductionunclassified

Investigação Dos Efeitos Do Ácido 2,4 Diclorofenoxiacético Sobre Diferentes Populações De Neurônios Mioentéricos Do Duodeno De Ratos

Diamante

Ribeiro

Tibúrcio

et al. 2015

ArqVet

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DIAMANTE, N. A.; RIBEIRO, A. A.; TIBÚRCIO, V. G.; ROVIDA, A. F. S.; MARI, R. de B.; STABILLE, S. R.; GERMANO, R. M. Investigação dos efeitos do ácido 2,4 diclorofenoxiacético sobre diferentes populações de neurônios mioentéricos do duodeno de ratos. Arq. Ciênc. Vet. Zool. UNIPAR, Umuarama, v. 17, n. 2, p. 97-105, abr./jun. 2014. RESUMO:O herbicida mais usado, tanto em pequenas como em grandes propriedades, por isso mais amplamente estudado é o 2,4-D. Os estudos de toxicidade têm se concentrado sobre as alterações do sistema nervoso central, e por isto pouco se conhece sobre seus efeitos no sistema nervoso entérico. Com o objetivo de avaliar os efeitos do 2,4-D sobre os neurônios mioentéricos do duodeno de ratos foi fornecido durante 60 dias doses de 2,4-D na concentração de 5mg/kg de peso de corpóreo para ratosWistarde dois grupos experimentais (n=5). Os animais dos grupos controle permaneceram o mesmo período sem receber 2,4-D. Ao final do período experimental os animais foram mortos, os duodenos foram coletados e processados por meio das técnicas histoquímicas de NADH-diaforase e NADPH-diaforase. Os neurônios foram quantificados e os resultados foram analisados estatisticamente. A densidade dos neurônios NADHd diferiu estatisticamente (P˂0,05) entre os grupos experimental e controle, sendo maior no grupo controle. Já os neurônios NADPHd foram encontrados em maior quantidade no grupo experimental. Estes resultados sugerem que o 2,4-D possui ação neurotóxica sobre os neurônios do plexo mioentérico, interferindo na densidade neuronal mioentérica, quando se compara diferentes populações destes neurônios. PALAVRAS-CHAVE: Plexomioentérico. Plasticidade neuronal. Intestino delgado. Herbicidas. INVESTIGATION OF 2,4 DICHLOROPHENOXYACETIC ACID EFFECTS IN DIFFERENT POPULATION OF RAT DUODENUM MYENTERIC NEURONS ABSTRACT:The 2,4-D herbicide is the most widely used, both in small and in large properties. Therefore, it is also the one that is most broadly studied. Toxicity studies have been focused on changes in the central nervous system, and for this reason, little is known about its effect in the enteric nervous system. With the objective of measuring the effects of 2,4-D on the myenteric neurons in the duodenum of rats, doses of 2,4-D were supplied for 60 days at a concentration of 5mg/kg of body weight to Wistar rats divided into two different experimental groups (n=5). The animals in the control groups remained without 2,4-D doses for the same period. At the end of the experimental period, the animals were euthanized and their duodenum were collected and processed through NADH-diaphorase and NADPH-diaphorase histochemical techniques. The neurons were quantified and the results were statistically analyzed. The density of NADHd neurons differed statistically (P<0,05) between the experimental and control groups, being higher in the control group. However, NADPHd neurons were found in a greater quantity in the experimental group. These results suggest that the 2,4-D has a neurotoxic action in the neurons from the myenteric ...

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Chronic Dietary Toxicity/Oncogenicity Studies on 2,4-Dichlorophenoxyacetic Acid in Rodents

Cited by 60 publications

References 16 publications

Genomic Sensitivity of Small Mammals - A Suitable Test System in the Genetic Monitoring

Genomic Sensitivity of Small Mammals - A Suitable Test System in the Genetic Monitoring

Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis

Investigação Dos Efeitos Do Ácido 2,4 Diclorofenoxiacético Sobre Diferentes Populações De Neurônios Mioentéricos Do Duodeno De Ratos

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