BACKGROUND: Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States. METHODS: This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes. RESULTS: After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P  < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P  = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses. CONCLUSIONS Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.
Adult ; Humans ; United States/epidemiology* ; Nitrates/adverse effects* ; Nutrition Surveys ; Thiocyanates/urine* ; Perchlorates/urine* ; Creatinine ; Environmental Exposure ; Renal Insufficiency, Chronic/epidemiology* ; Logistic Models

Perchlorate is an environmental pollutant that has been a focus of attention in recent years. It has been detected in many environmental water bodies and drinking water in China, with a high level of presence in some areas of the Yangtze River Basin. The human body may ingest perchlorate through exposure pathways such as drinking water and food, and its main health effect is to affect the thyroid's absorption of iodine. The "Standards for Drinking Water Quality" (GB5749-2022) includes perchlorate as an expanded indicator of water quality, with a limit value of 0.07 mg/L. This article analyzes the technical content related to the determination of hygiene standard limits for perchlorate in drinking water, including the environmental presence level and exposure status of perchlorate, main health effects, derivation of safety reference values, and determination of hygiene standard limits.
Humans ; Water Quality ; Drinking Water ; Perchlorates/analysis* ; China ; Water Pollutants, Chemical/analysis*

Ammonium perchlorate (AP), mainly used as solid propellants, was reported to interfere with homeostasis via competitive inhibition of iodide uptake. However, detailed mechanisms remain to be elucidated. In this study, AP was administered at 0, 130, 260 and 520 mg/kg every day to 24 male SD rats for 13 weeks. The concentrations of iodine in urine, serum thyroid hormones levels, total iodine, relative iodine and total protein, and malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activity in thyroid tissues were measured, respectively. Our results showed that high-dose perchlorate induced a significant increase in urinary iodine and serum thyroid stimulating hormone (TSH), with a decrease of total iodine and relative iodine content. Meanwhile, free thyroxine (FT4) was decreased and CAT activity was remarkably increased. Particularly, the CAT activity was increased in a dose-dependent manner. These results suggested that CAT might be enhanced to promote the synthesis of iodine, resulting in elevated urinary iodine level. Furthermore, these findings suggested that iodine in the urine and CAT activity in the thyroid might be used as biomarkers for exposure to AP, associated with thyroid hormone indicators such as TSH, FT4.
Analysis of Variance ; Animals ; Catalase ; metabolism ; Dose-Response Relationship, Drug ; Homeostasis ; drug effects ; Iodine ; metabolism ; urine ; Male ; Malondialdehyde ; metabolism ; Perchlorates ; pharmacology ; Quaternary Ammonium Compounds ; pharmacology ; Radioimmunoassay ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Thyroid Gland ; metabolism ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVETo understand the occupational hazards of ammonium perchlorate dust on operating workers and to provide the basis preventive measures for protecting the workers' health.

METHODS36 workers exposed to ammonium perchlorate dust and 48 unexposed workers from one factory were selected as the exposure and control groups. Investigations on the general condition, sampling of dust in the workplaces and a special medical examination were conducted for two groups, including occupational history, clinical manifestations, blood routine test, hepatic and renal functions, indexes of thyroid hormone, spirometric test and chest X-ray.

RESULTSThe total dust concentration of AP in the batch plant reached to 51.63 ± 43.27 mg/m(3), exceeding the U.S. Occupational Safety and Health Administration (OSHA) permission exposure limits. The systolic blood pressure in the exposure group was higher than that of the control group (146.14 ± 21.03 VS 134.67 ± 18.58), and the difference was statistically significant (P < 0.05). The detection rates of the cumulative total symptoms, short of breath and skin itch symptoms in the exposure group were significantly higher than those in the control group (86.11% VS 66.67%; 30.56% VS 12.50%) (P < 0.05), respectively. FT(3) level in the exposure group significantly lowered than the control group, and the difference was statistically significant (P < 0.01); The pulmonary function result showed that FEV1/FVC% in the exposure group was lower than that in the control group (106.50 ± 28.99 VS 111.70 ± 19.72), but the difference was not significant. X-ray examination revealed one case of pulmonary X-ray abnormalities in the exposure group, diagnosis of pneumoconiosis, and one case with about 1.0 × 1.0 small nodules detected on the left of lung door area in the control group.

CONCLUSIONSThe systolic blood pressure of workers in the exposure group was significantly higher, which could not exclude related to the exposure to AP dust; The T(3) levels in the exposure workers were lower than those in the control group, which may due to AP exposure, suggesting that long-term chronic exposure to AP dust may affect thyroid function.

Adult ; Air Pollutants, Occupational ; Blood Pressure ; Case-Control Studies ; Dust ; Female ; Health Surveys ; Humans ; Male ; Middle Aged ; Multiphasic Screening ; Occupational Exposure ; Perchlorates ; adverse effects ; Quaternary Ammonium Compounds ; adverse effects ; Thyroid Function Tests

OBJECTIVETo investigate the mechanism of thyroid cytotoxicity mechanism of ammonium perchlorate (AP).

METHODSThyroid cells were cultured in vitro to a certain stage and then exposed to AP (0, 5, 10, 20, 40, and 60 mmol/L) in culture solution; the cultured cells and supernatant were collected. Cell viability was measured by MTT assay; cell apoptosis was determined by flow cytometry; the concentration of thyroglobulin was measured by enzyme-linked immunosorbent assay; the lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, and so on were measured by colorimetry.

RESULTSThe cells exposed to 60 mmol/L AP for 12, 24, 48, and 72 h had cell viabilities of 74.93%, 42.26%, 2.66%, and 0.99%, respectively, and the cells exposed to 40 mmol/L AP for 24, 48, and 72 h had cell viabilities of 73.15%, 30.91%, and 3.03%, respectively, all significantly lower than that of the control group (100%)(P < 0.05 or P < 0.01). The overall apoptosis rate of all AP-exposed cells was significantly higher than that of the control group; the cells exposed to 20, 40, and 60 mmol/L AP had early apoptosis rates of 15.70%, 15.84%, and 16.96%, respectively, significantly higher than that of the control group (9.54%)(P < 0.05 or P < 0.01); the cells exposed to 60 mmol/L AP had a late apoptosis rate of 16.54%, significantly higher than that of the control group (6.11%)(P < 0.05 or P < 0.01). The cells exposed to 40 mmol/L AP had a significantly higher LDH activity than the control group (0.70 U/ml vs 0.55 U/ml, P < 0.01). The cells exposed to 5 mmol/L AP had a significantly higher MDA level than the control group (1.08 mmol/L vs 2.36 mmol/L, P < 0.05).

CONCLUSIONAP can markedly change the cell morphology and decrease the cell viability of thyroid cells, which may be because AP inhibits cell proliferation, induces cell apoptosis, and destroys cell membranes. However, AP does not result in significant oxidative damage to thyroid cells.

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Humans ; Oxidative Stress ; Perchlorates ; toxicity ; Quaternary Ammonium Compounds ; toxicity ; Thyroglobulin ; metabolism ; Thyroid Gland ; drug effects ; metabolism ; pathology

Humans ; Perchlorates ; toxicity ; Thyroid Gland ; drug effects

OBJECTIVETo study the effects of ammonium perchlorate (AP) on the levels of thyroid hormone and the testis function of male rats.

METHODSTwenty male rats were randomly divided into 4 groups: control group, low, middle and high AP group. The rats were exposed orally to 0, 130, 260 and 520 mg AP/kg a day for 80 days. The levels of thyroid hormone, testosterone in serum and sperm motility were measured and the testis histological change was observed as well.

RESULTSThe increase of body weight in high AP group was significantly lower than that in the control group (P < 0.01). The organ coefficients of testis and thyroid in high AP group obviously enhanced, as compared with the control group (P < 0.01). The free thyroxin (FT4) levels of serum in all AP treated groups were significantly lower than that of the control group (P < 0.05). There were no differences of serum FT3 levels between all AP groups and control group, while serum TSH levels in middle and high AP groups decreased significantly, as compared with control group (P < 0.01). In terms of sperm motility, the percentage of Grade A and B sperm in middle and high groups were 12.3% +/- 2.52% and 14.8% +/- 5.93%, 17.7% +/- 4.63%, 15.8% +/- 2.28% respectively, which were significantly lower than that (27.8% +/- 8.70%) in control group (P < 0.01). The percentage of Grade D sperm in middle and high groups were 38.0% +/- 3.61% and 40.0% +/- 8.99%, respectively, which were significantly higher than that (17.0% +/- 5.00%) in control group (P < 0.01). No difference of serum testosterone level between all AP groups and control group was observed.

CONCLUSIONAP can influence the levels of thyroid hormone and reduce the serum FT4 levels in rats. The main toxic effects on male reproductive system may decrease the sperm motility.

Animals ; Male ; Perchlorates ; adverse effects ; Quaternary Ammonium Compounds ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects ; Testis ; drug effects ; Thyroid Gland ; drug effects ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVETo investigate the effects of ammonium perchlorate (AP) on thyroid functions and mRNA expression levels of thyroglobulin (Tg) and thyroperoxidase (TPO) genes of rats.

METHODSThirty SD male rats were randomly divided into six groups: control group, iodine-deficient group, low dose AP group (130 mg/kg), moderate dose AP group (260 mg/kg), high dose AP group (520 mg/kg) and high iodine-combined group. After the rats were exposed orally for 90 days, serum free-thyroxine (FT(4)), free-triiodothyronine (FT(3)) and thyroid stimulating hormone (TSH) were measured using radioimmunoassays. mRNA expression levels of thyroglobulin (Tg) and thyroperoxidase (TPO) genes were detected by real-time quantitative PCR.

RESULTSSerum FT(4) levels in moderate dose AP group and high dose AP group were [(9.540 ± 1.327) fmol/ml] and [(6.509 ± 1.949) fmol/ml] respectively, which were significantly lower than that [(13.505 ± 1.276) fmol /ml] in control group (P < 0.05 or P < 0.01). Serum TSH level in high dose AP group was [(1.227 ± 0.295) mIU/L], which was significantly higher than that [(0.545 ± 0.282) mIU/L] in control group (P < 0.05). The mRNA expression levels of thyroglobulin (Tg) gene in all groups exposed to AP were significantly lower than that in control group (P < 0.01). The mRNA expression level of thyroperoxidase (TPO) gene in high dose AP group was significantly higher than that in control group (P < 0.05).

CONCLUSIONAP can reduce the serum FT(3) and FT(4) levels of rats, increase the serum TSH level of rats and decrease obviously the mRNA expression levels of Tg and TPO genes. In addition, high iodine can reduce the toxic effects of AP on thyroid gland of rats to some extent.

Animals ; Iodide Peroxidase ; genetics ; metabolism ; Iodine ; administration & dosage ; Male ; Perchlorates ; toxicity ; Quaternary Ammonium Compounds ; toxicity ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Thyroglobulin ; genetics ; metabolism ; Thyroid Gland ; drug effects ; metabolism ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVETo investigate the effect of dracorhodin perchlorate (DP) on inhibiting high glucose-induced serum and glucocorticoid induced protein kinase 1 (SGK1) and fibronectin (FN) expression in human mesangial cells (HMC), and its mechanism of prevention and treatment on renal fibrosis in diabetic nephropathy (DN) .

METHODThe HMC were divided into normal glucose group (NG group, 5.5 mmol x L(-1) D-glucose), normal glucose +low DP group (NG + LDP group, 5.5 mmol x L(-1) D-glucose +7.5 micromol x L(-1) DP), normal glucose +high DP group (NG + HDP group, 5.5 mmol x L(-1) D-glucose + 15 micromol x L(-1) DP), high glucose group (HG group,25 mmol x L(-1) D-glucose), high glucose +low DP group (HG + LDP group, 25 mmol x L(-1) D-glucose + 7.5 micromol x L(-1) DP)and high glucose +high DP group (HG +HDP group, 25 mmol x L(-1) D-glucose + 15 micromol x L(-1) DP). Each group was examined at 24 hours. The levels of SGK1 and FN mRNA was detected by real-time fluorescence quantitative PCR,and the expression of SGK1 and FN protein was detected by Western blot or indirect immunofluorescence.

RESULTA basal level of SGK1 and FN in HMC were detected in NG group, and the level of SGK1 and FN mRNA and protein were not evidently different compared to that of NG group adding 7.5 micromol x L(-1) DP for 24 hours. On the other hand, the levels of SGK1 and FN mRNA and protein were obviously decreased by adding 15 micromol x L(-1) DP for 24 hours. Compared to NG group, the levels of SGK1 and FN mRNA and protein were increased in HG group after stimulating for 24 hours (P < 0.01). Compared to HG group, the level of SGK1 and FN mRNA and protein were evidently reduced in HG + LDP and HG + HDP groups by adding 7.5 micromol x L(-1) DP and 15 micromol x L(-1) DP for 24 hours (P < 0.01).

CONCLUSIONDracorhodin perchlorate can inhibit high glucose-induced serum and glucocorticoid induced protein kinase 1 (SGK1) and fibronectin(FN) expression in human mesangial cells, and this may be part of the mechanism of preventing and treating renal fibrosis of DN.

Benzopyrans ; pharmacology ; Cell Line ; Diabetic Nephropathies ; drug therapy ; enzymology ; genetics ; metabolism ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Fibronectins ; biosynthesis ; genetics ; Gene Expression ; drug effects ; Glucose ; metabolism ; Humans ; Immediate-Early Proteins ; genetics ; metabolism ; Mesangial Cells ; drug effects ; enzymology ; metabolism ; Perchlorates ; pharmacology ; Protein-Serine-Threonine Kinases ; genetics ; metabolism

Animals ; Endocrine Disruptors ; toxicity ; Lethal Dose 50 ; Perchlorates ; toxicity ; Quaternary Ammonium Compounds ; toxicity ; Thyrotropin ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism