In vivo micronucleus assays on 2,4-dichlorophenoxyacetic acid and its derivatives

Charles, Jeffrey M.; Cunny, Helen; Wilson, Ronald D.; Ivett, J. L.; Murli, Hemalatha; Bus, James S.; Gollapudi, B. Bhaskar

doi:10.1016/s1383-5718(99)00076-5

Cited by 38 publications

(10 citation statements)

References 13 publications

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“…Animal studies in vitro are equivocal, with some suggesting that 2,4-D and/or MCPA are able to cause chromosomal aberrations and interrupt key cellular functions while others do not (summarized in Table 9), but generally showing effects at concentrations exceeding renal transport mechanisms. Studies involving human cell cultures or human cells derived from in vivo exposures do suggest that 2,4-D and/or MCPA are capable of causing chromosomal aberrations in some studies [186, 188, 191, 212] but not in others [19, 181], and both 2,4-D and MCPA showed negative results across a battery of ToxCat genotoxicity assays [211]. Interestingly, some positive associations are noted for exposure to a commercial product containing 2,4-D but not for the pure 2,4-D acid or salt [21, 193].…”

Section: Discussionmentioning

confidence: 99%

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A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Stackelberg

2013

Journal of Toxicology

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Chlorophenoxy compounds, particularly 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxy)acetic acid (MCPA), are amongst the most widely used herbicides in the United States for both agricultural and residential applications. Epidemiologic studies suggest that exposure to 2,4-D and MCPA may be associated with increased risk non-Hodgkins lymphoma (NHL), Hodgkin's disease (HD), leukemia, and soft-tissue sarcoma (STS). Toxicological studies in rodents show no evidence of carcinogenicity, and regulatory agencies worldwide consider chlorophenoxies as not likely to be carcinogenic or unclassifiable as to carcinogenicity. This systematic review assembles the available data to evaluate epidemiologic, toxicological, pharmacokinetic, exposure, and biomonitoring studies with respect to key cellular events noted in disease etiology and how those relate to hypothesized modes of action for these constituents to determine the plausibility of an association between exposure to environmentally relevant concentrations of 2,4-D and MCPA and lymphohematopoietic cancers. The combined evidence does not support a genotoxic mode of action. Although plausible hypotheses for other carcinogenic modes of action exist, a comparison of biomonitoring data to oral equivalent doses calculated from bioassay data shows that environmental exposures are not sufficient to support a causal relationship. Genetic polymorphisms exist that are known to increase the risk of developing NHL. The potential interaction between these polymorphisms and exposures to chlorophenoxy compounds, particularly in occupational settings, is largely unknown.

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Section: Discussionmentioning

confidence: 99%

“…Charles et al [181] conducted in vitro unscheduled DNA synthesis assays on male Fischer 344 rat hepatocytes using parent 2,4-D compound and seven derivatives of salts, esters, and amines. Plate concentrations ranged from 2 to 340 μ g/L, and no effects were observed.…”

Section: Toxicological Studiesmentioning

confidence: 99%

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Stackelberg

2013

Journal of Toxicology

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“…The phenoxy herbicides have been one of the most commonly studied groups of pesticides. Genetic in vitro toxicity testing on the phenoxy herbicide 2,4-D has reportedly been negative (23). Paternally mediated reproductive toxicity of a picloram and 2,4-D combination herbicide has been suggested in mice (24).…”

Section: Discussionmentioning

confidence: 99%

An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population.

Arbuckle

Lin

Mery

2001

Environ Health Perspect

238

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The toxicity of pesticides on human reproduction is largely unknown--particularly how mixtures of pesticide products might affect fetal toxicity. The Ontario Farm Family Health Study collected data by questionnaire on the identity and timing of pesticide use on the farm, lifestyle factors, and a complete reproductive history from the farm operator and eligible couples living on the farm. A total of 2,110 women provided information on 3,936 pregnancies, including 395 spontaneous abortions. To explore critical windows of exposure and target sites for toxicity, we examined exposures separately for preconception (3 months before and up to month of conception) and postconception (first trimester) windows and for early (< 12 weeks) and late (12-19 weeks) spontaneous abortions. We observed moderate increases in risk of early abortions for preconception exposures to phenoxy acetic acid herbicides [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.1-2.1], triazines (OR = 1.4; 95% CI, 1.0-2.0), and any herbicide (OR = 1.4; 95% CI, 1.1-1.9). For late abortions, preconception exposure to glyphosate (OR = 1.7; 95% CI, 1.0-2.9), thiocarbamates (OR = 1.8; 95% CI, 1.1-3.0), and the miscellaneous class of pesticides (OR = 1.5; 95% CI, 1.0-2.4) was associated with elevated risks. Postconception exposures were generally associated with late spontaneous abortions. Older maternal age (> 34 years of age) was the strongest risk factor for spontaneous abortions, and we observed several interactions between pesticides in the older age group using Classification and Regression Tree analysis. This study shows that timing of exposure and restricting analyses to more homogeneous endpoints are important in characterizing the reproductive toxicity of pesticides.

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“…Gonzalez et al (2005) found that doses of 6 ppm and 10 ppm 2,4-D increased sister chromatid exchanges, reduced mitotic index and increased DNA damage in Chinese hamster ovary cells. In studies in mice Charles et al (1999) indicated that 2,4-D clearly demonstrates a lack of cytogenetic damage at any dose level in the bone marrow micronucleus test. These authors also concluded that 2,4-D is not genotoxic in mammalian systems in vivo.…”

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

confidence: 98%

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

Topashka-Ancheva¹,

Gerasimova²

2012

Ecotoxicology

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In vivo micronucleus assays on 2,4-dichlorophenoxyacetic acid and its derivatives

Cited by 38 publications

References 13 publications

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population.

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

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