Andrea Corrales Vargas1, Jorge Peñaloza Castañeda1, Emelie Rietz Liljedahl2, Ana María Mora3, Jose Antonio Menezes-Filho4, Donald R Smith5, Donna Mergler6, Brian Reich7, Andrew Giffin7, Jane A Hoppin8, Christian H Lindh2, Berna van Wendel de Joode9. 1. Infants' Environmental Health Study (ISA), Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica. 2. Division of Occupational and Environmental Medicine, Institute of Laboratory Medicine, Lund University, SE-221 85 Lund, Sweden. 3. Infants' Environmental Health Study (ISA), Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica; Center for Environmental Research and Children's Health (CERCH), University of California at Berkeley, United States. 4. Laboratory of Toxicology, College of Pharmacy, Federal University of Bahia, Av. Barão de Jeremoabo s/n Campus Universitário de Ondina, 40170-115 Salvador, Bahia, Brazil. 5. Microbiology and Environmental Toxicology, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, United States. 6. Centre de recherche interdisciplinaire sur le bien-être, la santé, la société et l'environnement (CINBIOSE), Université du Québec à Montréal, Montreal, Canada. 7. Department of Statistics, North Carolina State University, United States; Center for Human Health and the Environment, North Carolina State University, United States. 8. Center for Human Health and the Environment, North Carolina State University, United States; Department of Biological Sciences, North Carolina State University, United States. 9. Infants' Environmental Health Study (ISA), Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica. Electronic address: berendina.vanwendel.dejoode@una.cr.
Abstract
BACKGROUND: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development. OBJECTIVES: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). METHODS: At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (μg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (μg/g) and blood (MnB) (μg/L), and blood lead (PbB) (μg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression. RESULTS: About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: β = -0.79 (95%CI = -1.51, -0.08) and β = -0.29 (95%CI = -0.62, -0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (β = 0.04 (95%CI = 0.00, 0.07 per 1 μg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3. DISCUSSION: Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action.
BACKGROUND: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development. OBJECTIVES: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). METHODS: At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (μg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (μg/g) and blood (MnB) (μg/L), and blood lead (PbB) (μg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression. RESULTS: About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: β = -0.79 (95%CI = -1.51, -0.08) and β = -0.29 (95%CI = -0.62, -0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (β = 0.04 (95%CI = 0.00, 0.07 per 1 μg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3. DISCUSSION: Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action.
Authors: Daniel R Hallinger; Ashley S Murr; Angela R Buckalew; Steven O Simmons; Tammy E Stoker; Susan C Laws Journal: Toxicol In Vitro Date: 2016-12-12 Impact factor: 3.500
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