Ames assays and unscheduled DNA synthesis assays on 2,4-dichlorophenoxyacetic acid and its derivatives

Charles, Jeffrey M.; Cunny, Helen; Wilson, Ronald D.; Bus, James S.; Lawlor, Timothy E.; Cifone, Maria A.; Fellows, Michael; Gollapudi, B. Bhaskar

doi:10.1016/s1383-5718(99)00074-1

Cited by 36 publications

(6 citation statements)

References 11 publications

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“…1 and 2). This negative response coincides with earlier in vitro and in vivo studies [Fahrig 1974;Vogel and Chandler, 1974;Jenssen and Renberg, 1976;Zetterberg et al, 1977;Simmon, 1979;Charles et al, 1999aCharles et al, ,b, 2000Gollapudi et al, 1999]. The lack of effect of Fe oxidation state on the transformation of 2,4-D agrees with an earlier study on chronic mammalian cell cytotoxicity [Sorensen et al, 2004].…”

Section: Discussionsupporting

confidence: 90%

Modulation of the genotoxicity of pesticides reacted with redox‐modified smectite clay

Sorensen¹,

Stucki²,

Warner³

et al. 2005

Environ and Mol Mutagen

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Pesticides are toxic agents intentionally released into the environment; their use raises public health and environmental concerns. In recent years there has been much attention to the biotic degradation of pesticides. Abiotic mechanisms in the soil can contribute to pesticide degradation yet the toxicological impact of such degradation is unclear. This study combines for the first time an investigation into abiotic mechanisms of degradation coupled with toxicological endpoints in mammalian cells. The genotoxicity of three commonly used agricultural pesticides was assessed before and after exposure to redox-modified clay minerals. The objectives of the study were to determine the genotoxicity of 2,4-dichlorophenoxy acetic acid (2,4-D), dicamba, and oxamyl, using single cell gel electrophoresis with Chinese hamster ovary (CHO) cells, and to determine the effect of the iron oxidation state in clay minerals (ferruginous smectite SWa-1) on the genotoxic potency of the pesticides. 2,4-D alone or following reaction with redox-modified clays did not induce DNA damage in CHO cells. Oxamyl alone induced a concentration-dependent increase in genomic DNA damage; however, its genotoxicity declined after reaction with reduced clay minerals. Dicamba was not genotoxic when directly analyzed. When dicamba was reacted with reduced clay, a concentration-dependent increase in genomic DNA damage was observed. This is the first reported case of a pesticide being converted into a genotoxin after exposure to redox-modified smectites. These data introduce a new paradigm on the interaction between redox-modified clays and pesticide-related environmental genotoxicity.

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Section: Discussionsupporting

confidence: 90%

Modulation of the genotoxicity of pesticides reacted with redox‐modified smectite clay

Sorensen¹,

Stucki²,

Warner³

et al. 2005

Environ and Mol Mutagen

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“…In the same study, the authors also conducted the Ames bacterial reverse mutation assay (including a positive control) and found no effects across all treatment types. A follow-on study [185] evaluated the potential for 2,4-D and seven of its salts and esters to induce cytogenetic abnormalities in mammalian cells in vivo using the mouse bone marrow micronucleus test in CD-1 mice. All the test materials were administered to male and female mice by oral gavage, and the frequencies of micronucleated polychromatic erythrocytes MN-PCE in bone marrow were determined at intervals of 24, 48, and 72 h following dosing.…”

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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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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“…The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is not genotoxic and has shown no evidence of carcinogenicity in laboratory animals [1–5]. However, the carcinogenicity of 2,4-D in humans has been actively debated since an early case-control report of non-Hodgkin lymphoma (NHL) and herbicide use by farmers [6].…”

Section: Introductionmentioning

confidence: 99%

Cancer Incidence of 2,4-D Production Workers

Burns

Bodner

Swaen

et al. 2011

IJERPH

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Despite showing no evidence of carcinogenicity in laboratory animals, the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been associated with non-Hodgkin lymphoma (NHL) in some human epidemiology studies, albeit inconsistently. We matched an existing cohort of 2,4-D manufacturing employees with cancer registries in three US states resulting in 244 cancers compared to 276 expected cases. The Standardized Incidence Ratio (SIR) for the 14 NHL cases was 1.36 (95% Confidence Interval (CI) 0.74–2.29). Risk estimates were higher in the upper cumulative exposure and duration subgroups, yet not statistically significant. There were no clear patterns of NHL risk with period of hire and histology subtypes. Statistically significant results were observed for prostate cancer (SIR = 0.74, 95% CI 0.57–0.94), and “other respiratory” cancers (SIR = 3.79, 95% CI 1.22–8.84; 4 of 5 cases were mesotheliomas). Overall, we observed fewer cancer cases than expected, and a non statistically significant increase in the number of NHL cases.

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Ames assays and unscheduled DNA synthesis assays on 2,4-dichlorophenoxyacetic acid and its derivatives

Cited by 36 publications

References 11 publications

Modulation of the genotoxicity of pesticides reacted with redox‐modified smectite clay

Modulation of the genotoxicity of pesticides reacted with redox‐modified smectite clay

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

Cancer Incidence of 2,4-D Production Workers

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