Change of iodine load and thyroid homeostasis induced by ammonium perchlorate in rats / 华中科技大学学报（医学）（英德文版）

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.

Change of iodine load and thyroid homeostasis induced by ammonium perchlorate in rats / 华中科技大学学报（医学）（英德文版）

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.

Health survey of plant workers for an occupational exposure to ammonium perchlorate / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To understand the occupational hazards of ammonium perchlorate dust on operating workers and to provide the basis preventive measures for protecting the workers' health.</p><p><b>METHODS</b>36 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSIONS</b>The 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.</p>

Study on mechanism of thyroid cytotoxicity of ammonium perchlorate / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of thyroid cytotoxicity mechanism of ammonium perchlorate (AP).</p><p><b>METHODS</b>Thyroid 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>AP 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.</p>

Study of genotoxicity and oxidative stress induced by copper oxide nanoparticles in mice / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the genotoxicity and oxidative stress induced by copper oxide nanoparticles in mice.</p><p><b>METHODS</b>Thirty mice were randomly divided into control group and low- and high-dose exposure groups. The low- and high-dose exposure groups were given copper oxide nanoparticles (50 and 150 mg/kg) by a single intraperitoneal injection, while the control group was given an equal volume of normal saline containing 0.05%Tween 80. The micronucleus rate of reticulocytes in peripheral blood from the caudal vein and urinary 8-hydroxy-deoxyguanosine (8-OH-dG) level were measured before and at 24, 48, and 72 h after exposure. All the mice were sacrificed at 72 h after exposure, the liver, kidney, and femoral marrow were taken for DNA extraction, and 8-OH-dG in DNA was quantified.</p><p><b>RESULTS</b>The micronucleus rates of peripheral blood reticulocytes in low-dose exposure group at 48 h (3.11±1.46‰ and in high-dose exposure group at 24 and 48 h (4.25±0.43) and 5.42±0.76‰) were significantly increased compared with those before exposure (1.55±0.39‰ and 1.11±0.19‰) and those in control group (1.55±0.28‰ and 1.00±0.67‰) (P < 0.05 or P < 0.01). The urinary 8-OH-dG levels (ng/mg creatinine) in low- and high-dose exposure groups at all time points were significantly increased compared with those before exposure and those in control group (P < 0.05 or P < 0.01). The low- and high-dose exposure groups had significantly higher content of 8-OH-dG in liver DNA than the control group (4.53±1.27 and 7.69±2.78 vs 0.85±0.14, P < 0.01).</p><p><b>CONCLUSION</b>Copper oxide nanoparticles cause genotoxicity and increase oxidative stress in mice.</p>

The effects of ammonium perchlorate on thyroid function and testis in male rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effects of ammonium perchlorate (AP) on the levels of thyroid hormone and the testis function of male rats.</p><p><b>METHODS</b>Twenty 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>AP 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.</p>

The effects of ammonium perchlorate on thyroid function and mRNA expression of thyroglobulin and thyroperoxidase / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of ammonium perchlorate (AP) on thyroid functions and mRNA expression levels of thyroglobulin (Tg) and thyroperoxidase (TPO) genes of rats.</p><p><b>METHODS</b>Thirty 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.</p><p><b>RESULTS</b>Serum 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).</p><p><b>CONCLUSION</b>AP 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.</p>

Expressions of collagen in lung of rats exposed to ammonium perchlorate / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the influence on expression of interstitial collagen in lung of rats exposed to ammonium perchlorate.</p><p><b>METHODS</b>The rats were treated with AP by intratracheal instillation and sacrificed after 3 d, 7 d, 14 d, 28 d. The mRNA level of collagen I and collagen III in the lung tissues was measured by RT-PCR.</p><p><b>RESULTS</b>The levels of collagen I on 7 d, 14 d, 28 d exposed for high dose group (1.93 +/- 0.41, 3.50 +/- 0.90, 2.33 +/- 1.12) and 28 d exposed for medial dose group (2.58 +/- 0.86) were higher significant (P < 0.05) than those in negative control group (0.52 +/- 0.11, 0.77 +/- 0.15, 0.86 +/- 0.29) The levels of collagen I in low dose group exposed for 14 d(1.99 +/- 0.67), 28 d(1.85 +/- 0.67) and high dose group 14 d(3.50 +/- 0.90) exposed for 14 d were higher significant (P < 0.05) compared to those exposed to AP for 3 d(0.52 +/- 0.14), (1.71 +/- 0.38). The levels of collagen III on 14 d, 28 d exposed for high dose group (2.60 +/- 1.00, 1.46 +/- 0.36) and 14 d, 28 d exposed for medial dose group (1.80 +/- 0.51, 2.16 +/- 0.87) were higher significant (P < 0.05 or P < 0.01) than those in negative control group(0.54 +/- 0.20, 0.52 +/- 0.22); The levels of collagen III in medial dose group(2.16 +/- 0.87) exposed for 28 d, and high dose group exposed for 14 d (2.60 +/- 1.00) were higher significant (P < 0.05) compared to those exposed to AP for 3 d(1.22 +/- 0.32, 0.96 +/- 0.17).</p><p><b>CONCLUSION</b>The results suggest that AP has a toxic effect to promote the expressions of collagen I and collagen III mRNA in lungs of rats, and may be cause fibrosis, but there should have more suffice evidences to prove that AP is exactly compound that made lung fibrosis.</p>

Early change of pulmonary ventilation in new coal miners / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the early effects of coal dust on lung function in new underground coal miners.</p><p><b>METHODS</b>Two hundred and eighty-seven male miners were selected from new employees at the Xuzhou Mining Group Company as study group, and 132 male students at a mining technical school were selected as control. Data collection included: individual demographic parameters, family medical history, occupational history, and smoking history, measurement of dust concentrations in work areas, and lung function tests. This prospective cohort study took place over 3 years during which time total dust and respirable dust concentrations in the new coal miners' work areas were measured twice each month. For both miner and student groups, FVC and FEV(1) were tested initially before dust exposure, and then 15 times over the 3 years.</p><p><b>RESULTS</b>The average total dust and respirable dust concentrations in the miners' work areas were 23.8 mg/m(3) and 8.9 mg/m(3) respectively, which greatly exceeded national health criteria. During the first year of dust exposure, the miners's average FVC was higher than that of the controls (5.19 L vs 4.92 L, P < 0.01). During the 2nd and 3rd year the difference in average FVC between miners and control group was not significant (5.14 L vs 5.12 L, P > 0.05). Before dust exposure, the miners' FEV(1) was significantly higher than that of the control group (4.48 L vs 4.28 L). In the miners group, FEV(1) declined rapidly during the first year following dust exposure (from 4.48 L to 4.25 L), and in the 2nd and the 3rd year the average FEV(1) of the miners was significantly lower than that of controls (4.34 L vs 4.56 L, P < 0.01), although there were some fluctuations during the follow-up period. Overall, the average FEV(1) of miners group showed a significant decline during the study. There were significant correlations between FVC or FEV(1) and age, height, weight, and smoking. The three-year total loss of FVC and FEV(1) in smoking miners (154 ml, 184 ml) were greater than in non-smoking miners (83 ml, 91 ml).</p><p><b>CONCLUSION</b>There are apparent effects of coal dust on lung function in new underground coal miners, with FEV(1) being more impacted than FVC. Smoking may aggravate the effect of dust exposure on reducing lung function.</p>

Toxic effects of ammonium perchlorate on thyroid of rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effects of toxicity of ammonium perchlorate (AP) on thyroid of rats.</p><p><b>METHODS</b>Eighty-eight Wistar rats were treated orally with different dosages of AP. Three treated groups received 129, 257, 514 mg.kg(-1).d(-1) of AP respectively and one control group drunk water for 13 weeks. Another 3 groups received 1.2, 46.5, 465.0 mg.kg(-1).d(-1) of AP respectively and one control group drunk water for 36 weeks. The behavior and change of body weight in rats were observed. The levels of thyroid hormones in serum were measured and the pathological changes of thyroid tissue were observed as well.</p><p><b>RESULTS</b>There were no differences in behavior and change of body weight between different AP exposure time. When the rats were treated with AP 514 mg for 13 weeks, free triiodothyronine (FT3, 2.48 pmol/L), free thyroxin (FT4, 13.33 pmol/L) were lower than those in control group (3.24, 20.92 pmol/L respectively, P<0.05). Thyroid-stimulating hormone (TSH, 0.375 mIU/L), thyroglobulin (TG, 3.37 microg/L) were higher than those in control group (0.29 mIU/L, 2.00 microg/L respectively, P<0.05). When the rats were treated with AP 465 mg for 36 weeks, FT3 (2.65 pmol/L) was lower than that in control group (4.97 pmol/L, P<0.01). FT4 in 46.5, 465 mg groups (10.63, 2.17 pmol/L respectively) were lower than that in control group (15.74 pmol/L, P<0.05, P<0.01). TSH in 465 mg group (0.34 mIU/L) was higher than that in control group (0.14 mIU/L, P<0.05). Histopathologic examination showed that follicle proliferation, no colloid in follicle, gore, follicular diminishing or atresia were found in 46.5, 465 mg groups with a dose-effect relationship.</p><p><b>CONCLUSIONS</b>The toxic effects of AP on the growth of rats were not found, but those on the thyroid of rats were found significantly. Thyroid is the target organ of AP. It is considered that none effect dose of AP for rat thyroid may be 1.2 mg.kg(-1).d(-1), its threshold dose may be 46.5 mg.kg(-1).d(-1).</p>