Effect of para-nitrophenol concentration in urine of healthy adults on thyroid function based on US NHANES

Background  Parathion and methyl parathion are typical organophosphorus insecticides and para−nitrophenol (PNP) is their main specific metabolite. Previous studies have shown that parathion and methyl parathion may play a role as endocrine disrupting chemicals, but the evidence is limited.

Objective  Our aim is to evaluate association between urinary PNP concentration and thyroid function among healthy adults and whether this association has gender differences.

Methods  The study was based on the 2007—2008 US National Health and Nutrition ExaminationSurvey (NHANES). A total of 1071 subjects aging from 20 to 64 years with data on both urinary PNP and serum thyroid function indicators were finally enrolled. Thyroid function was evaluated by measuring serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroglobulin (TG), and thyroglobulin antibody (TG-Ab). A generalized linear model was used to analyze the relationship between urinary PNP and serum thyroid function indicators and the dose-response relationship. Gender differences were also explored.

Results  In the total population, the positive rate of PNP was 92.5%, and the median urinary PNP concentration adjusted for urinary creatinine was 0.62 μg·g⁻¹. The median creatinine-adjusted urinary PNP concentrations in the male and female populations were 0.60 and 0.66 µg·g⁻¹ respectively. The median activities or concentrations of serum thyroid function indicators TSH, FT3, FT4, TT3, and TT4 in the total population were 1500.00 μIU·L⁻¹, 3200.00 pg·L⁻¹, 8.00 ng·L⁻¹, 1140.00 ng·L⁻¹, and 76.00 μg·L⁻¹ respectively. In the total population, a logarithmic unit increase of urinary PNP was associated with 1050.00 pg·L⁻¹ decrease in serum FT3 levels (b=−0.02, 95%CI: −0.02-−0.01), 10.50 ng·L⁻¹ decrease in FT4 levels (b=−0.02, 95%CI: −0.03-−0.01), and 10.50 ng·L⁻¹ decrease in TT3 levels (b=−0.02, 95%CI: −0.03-−0.01), all in a dose-response manner (all P_trend<0.05). After sex stratification, for every logarithmic unit increase of urinary PNP, the serum TG-Ab level was increased by 1100.00 IU·L⁻¹ (b=0.04, 95%CI: 0.00-0.08) and the serum FT3 level was reduced by 1020.00 pg·L⁻¹ (b=−0.01, 95%CI: −0.02-0.00) among males, and both showed dose-response relationships (both P_trend<0.05); every logarithmic unit increase of urinary PNP was associated with 1050.00 pg·L⁻¹ decrease in FT3 levels (b=−0.02, 95%CI: −0.03-−0.01), 10.50 ng·L⁻¹decrease in FT4 levels (b=−0.02, 95%CI: −0.03-0.00), 10.70 ng·L⁻¹ decrease in TT3 levels (b=−0.03, 95%CI: −0.05-−0.01), and 10.50 μg·L⁻¹ decrease in TT4 levels (b=−0.02, 95%CI: −0.04-0.00) among females, and there were dose-response relationships of urinary PNP concentration with serum FT3 and TT3 levels (both P_trend<0.001).

Conclusion  Changes in the concentration of PNP in urine are associated with changes in serum FT4, FT3, and TT3 levels and the results also show gender differences.