Infants' Environmental Health Study (ISA), Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, Heredia, Costa Rica.
Division of Occupational and Environmental Medicine, Institute of Laboratory Medicine, Lund University, SE-221 85 Lund, Sweden.
Sci Total Environ. 2022 Mar 1;810:151288. doi: 10.1016/j.scitotenv.2021.151288. Epub 2021 Oct 28.
Pesticides and metals may disrupt thyroid function, which is key to fetal brain development.
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).
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.
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.
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.
农药和金属可能会扰乱甲状腺功能，而甲状腺功能对胎儿大脑发育至关重要。
评估孕妇当前使用的农药暴露、铅和过量锰是否会改变来自婴儿环境健康研究（ISA）的孕妇的游离甲状腺素（FT4）、游离三碘甲状腺原氨酸（FT3）和促甲状腺激素（TSH）浓度。
在入组时，我们确定了 400 名妇女（n=400）特异性比重校正尿液农药（μg/L）代谢产物的代森锰锌（乙撑硫脲（ETU））、嘧啶苯胺、噻苯达唑、毒死蜱、合成拟除虫菊酯和 2,4-D 的浓度。我们还测量了头发（MnH）（μg/g）和血液（MnB）（μg/L）中的锰，以及血液中的铅（PbB）（μg/L）浓度。为了检测对甲状腺稳态的即时和迟发影响，我们在同一就诊时（n=400）和大约十周后（n=245）获得了血清中的 TSH、FT4 和 FT3。我们使用线性回归和广义加性模型、贝叶斯多变量线性回归和贝叶斯核机器回归评估了暴露与结局之间的关系。
大约 80%、94%和 100%的妇女的 TSH、FT4 和 FT3 均在临床参考范围内。尿液中 ETU 和嘧啶苯胺代谢物水平较高的妇女的 FT4 水平较低：β= -0.79（95%CI= -1.51，-0.08）和β= -0.29（95%CI= -0.62，-0.03），每增加十倍暴露。MnB 与 FT4 呈正相关（β=0.04（95%CI=0.00，0.07 每增加 1μg/L），并且尿液中拟除虫菊酯代谢物浓度较高的妇女 TSH 降低（非线性效应）。对于晚期效应分析，拟除虫菊酯和毒死蜱的代谢物，以及 MnH 和 PbB 与降低 TSH、增加 FT4 和/或 FT3 有关。
代森锰锌（ETU）和嘧啶苯胺可能会抑制 FT4 的分泌（甲状腺功能减退样作用），而毒死蜱、拟除虫菊酯、MnB、MnH、PbB 和 Mn 则表现出甲状腺功能亢进样作用。一些对甲状腺稳态的影响似乎是即时的（代森锰锌（ETU）、嘧啶苯胺、MnB），另一些则是延迟的（毒死蜱、MnH、PbB），或者两者兼而有之（拟除虫菊酯），这可能反映了不同的作用机制。
