Biomarker Correlations of Urinary 2,4-D Levels in Foresters: Genomic Instability and Endocrine Disruption

Garry, Vincent F.; Tarone, Robert E.; Kirsch, Ilan R.; Abdallah, Jorge M.; Lombardi, Donald P.; Long, Linda; Burroughs, Barbara; Barr, Dana Boyd; Kesner, James S.

doi:10.2307/3454708

Cited by 17 publications

(22 citation statements)

References 12 publications

(15 reference statements)

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“…2,6,8,11,12) with recurrent birth defects had the same or similar birth defect. These findings are consistent with larger studies that demonstrate that families with one child with a birth defect are more likely to have a second child with the same or similar birth defect (6)(7)(8).…”

Section: Recurrent Birth Defectsmentioning

confidence: 97%

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

Garry

Harkins

Erickson

et al. 2002

Environ Health Perspect

208

119

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We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.3 births per 1,000, with 83% of the total reported birth defects confirmed by medical records. Inclusion of children identified with birth or developmental disorders within the first 3 years of life and later led to a rate of 47.0 per 1,000 (72 children from 1,532 live births). Conceptions in spring resulted in significantly more children with birth defects than found in any other season (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n = 28 children). Forty-two percent of the children from families with recurrent birth defects were conceived in spring, a significantly higher rate than that for any other season. Three families in the kinships defined contributed a first-degree relative other than a sibling with the same or similar birth defect, consistent with a Mendelian inheritance pattern. The remaining nine families did not follow a Mendelian inheritance pattern. The sex ratio of children with birth defects born to applicator families shows a male predominance (1.75 to 1) across specific pesticide class use and exposure categories exclusive of fungicides. In the fungicide exposure category, normal female births significantly exceed male births (1.25 to 1). Similarly, the proportion of male to female children with birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic and neurobehavioral developmental effects clustered among the children born to applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6 (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out that (a) herbicides applied in the spring may be a factor in the birth defects observed and (b) fungicides can be a significant factor in the determination of sex of the children of the families of the RRV. Thus, two distinct classes of pesticides seem to have adverse effects on different reproductive outcomes. Biologically based confirmatory studies are needed.

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Section: Recurrent Birth Defectsmentioning

confidence: 97%

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

Garry

Harkins

Erickson

et al. 2002

Environ Health Perspect

208

119

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“…The Lerda and Rizzi (1991) study is considered too limited in scope and relevant details, and is not considered to provide reliable evidence of male reproductive toxicity or endocrine disruption resulting from occupational exposure to 2,4-D. Swan et al (2003) is considered too limited, due to the low numbers of control and case subjects with urinary 2,4-D levels above the LOD, to be considered in the WoE as evidence for presence or absence of an association. Garry et al (2001) found no correlation between FSH, free testosterone, or total testosterone concentrations with 2,4-D urinary levels at the time of maximum 2,4-D usage. LH levels were reported to show a correlation, but the authors indicated the limited sample size warrants caution in drawing any conclusions from this study.…”

Section: Epidemiological Studiesmentioning

confidence: 64%

“…Three limited epidemiological studies evaluating potential associations of 2,4-D and changes in human sperm parameters (Lerda & Rizzi 1991;Swan et al 2003) or hormonal biomarkers (Garry et al 2001) were identified. The Lerda and Rizzi (1991) study is considered too limited in scope and relevant details, and is not considered to provide reliable evidence of male reproductive toxicity or endocrine disruption resulting from occupational exposure to 2,4-D. Swan et al (2003) is considered too limited, due to the low numbers of control and case subjects with urinary 2,4-D levels above the LOD, to be considered in the WoE as evidence for presence or absence of an association.…”

Section: Epidemiological Studiesmentioning

confidence: 99%

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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“…Where available, STROBE and NOS scores identified the same studies as being of a high quality (with exceptions of Garry et al, 2001 andSimcox et al, 1999 which had lower NOS scores).…”

Section: Identification Of Higher Quality Studiesmentioning

confidence: 88%

Human biomonitoring data collection from occupational exposure to pesticides

Bevan¹,

Brown²,

Matthies³

et al. 2017

EFSA Supporting Publications

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Human biomonitoring (HBM) as a tool for occupational exposure assessment has been reviewed, with a specific focus on pesticides. A systematic literature review (SLR) of available information on HBM of pesticides (or their metabolites) in occupational settings and from HBM studies/surveillance programmes has been carried out and the studies identified assessed for relevance and quality. HBM essentially involves the quantification of either a substance, one of its metabolites, or a surrogate marker of its effects in a biological sample obtained from a person who may have undergone an exposure. Thus, HBM is generally considered to be an estimate of exposure, rather than a measure of health. Over the past 10 to 20 years there has been an expansion in the use of HBM, especially into the field of environmental and consumer exposure analysis, and it is currently well-developed and widely used in both the occupational and environmental settings worldwide. As with any tool, HBM has its strengths and weaknesses and appreciation of these promotes the development of approaches to minimise their effects. Although HBM has been extensively used for monitoring worker exposure to a variety of pesticides, epidemiological studies of occupational pesticide use were seen to be limited by inadequate or retrospective exposure information. Very limited data was identified examining seasonal exposures and the impact of PPE, and many of the studies used HBM to assess only one or two specific compounds. A wide variety of exposure models are currently employed for health risk assessments and biomarkers are often used to evaluate exposure estimates predicted by a model. From the 178 publications identified to be of relevance, 41 individual studies included herbicides, 79 individual studies included insecticides, and 20 individual studies included fungicides. Remaining studies related to mixtures or non-specific biomarkers for groups of pesticides. Although a number of current limitations were identified, there is evidence within the literature for a potential role of HBM in occupational health and safety strategies, as both a tool for refined exposure assessment in epidemiology studies and to contribute to the evaluation of potential health risks from occupational exposure to pesticides. Some key issues were considered that would need to be overcome to enable implementation of HBM as part of the occupational health surveillance for pesticides in Europe. These included issues around priorities for the development of new specific and sensitive biomarkers, the derivation and adoption of health-based guidance values, development of QA schemes to validate inter-laboratory measurements, good practice in field work and questionnaire design, consideration of the extended use of biobanking and the use of HBM for post-approval monitoring of pesticide safety.

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Biomarker Correlations of Urinary 2,4-D Levels in Foresters: Genomic Instability and Endocrine Disruption

Cited by 17 publications

References 12 publications

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

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

Human biomonitoring data collection from occupational exposure to pesticides

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