Urinary arsenic metabolites in children and adults exposed to arsenic in drinking water in Inner Mongolia, China

BACKGROUND: We report the concentrations and distributions of urinary arsenic (As) metabolites in 233 residents exposed to 20, 90, or 160 microg/L inorganic arsenic (iAs) in drinking water from three villages in Hohhot, Inner Mongolia, China, that formed one control and two exposed groups. METHODS: We used hydride generation-atomic absorption spectrometry (HGAAS) to determine iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). RESULTS: The concentrations of each urinary As species in the two exposed groups were significantly higher than in the control group for both children and adults. Both children and adults in exposed groups had higher percent iAs and MMA and lower percent DMA, and low primary and secondary methylation indices (PMI and SMI, respectively) than those in the control group. However, children showed significant increases in percent DMA and the SMI as well as decreases in the percent MMA when the iAs exposure level increased from 90 to 160 microg/L. In addition, children in the two exposed groups showed lower percent MMA but higher percent DMA and higher SMI than adults in the same exposed group. No significant differences in As metabolite concentrations and distributions were found between males and females in each group. A significant correlation was also found in the SMI between 11 pairs of children and their mothers from the 160-microg/L-exposed group. CONCLUSIONS: Children had higher a capacity for secondary methylation of As than adults when exposed to the same concentrations of iAs in drinking water. Exposure to As may increase the capacity for methylation in children to some extent.     

Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.     

Urinary protein excretion in humans exposed to arsenic and cadmium

OBJECTIVE: In mice, the renal toxicity of arsenic (As) and cadmium (Cd) has been shown to be exacerbated by the simultaneous administration of both elements. To verify the existence of such an interaction in humans, cohorts slightly (Belgian) and moderately (Chinese) exposed to both elements were examined. METHODS: Biological indicators of exposure (Cd in urine and in blood; As in urine) and renal effect parameters (retinol binding protein (RBP); beta(2)-microglobulin (beta(2)M); albumin (ALB); N-acetyl-beta-glucosaminidase (NAG) in urine) were determined and their relationships studied by multiple regression analyses. RESULTS: Changes in renal effect parameters could be ascribed to Cd body burden. RBP and beta(2)M urinary concentration were influenced by exposure to As only in Chinese women, directly and in interaction with Cd exposure. CONCLUSION: A synergistic action of As on the tubular effects of Cd is observed in women moderately exposed to these elements and leads to RBP urinary excretion slightly above normal values.     

广西不同煤质煤矿尘肺流行病学比较分析

目的探讨不同煤质煤尘对尘肺患病的影响。方法用回顾性流行病学方法对广西3种不同煤质的12个煤矿进行尘肺患病率、历年粉尘浓度、粉尘游离二氧化硅含量情况进行调查分析。结果褐煤、烟煤、无烟煤作业场所历年平均粉尘浓度（mg／m^3）分别为68．75、24．01、17．18,游离二氧化硅含量（％）分别为11,07、59．77和13,78。褐煤、烟煤、无烟煤煤矿工人尘肺患病率（％）分别为0．15、6．70、1．58。褐煤矿接尘工人尘肺患病率明显低于烟煤、无烟煤矿工人（P〈0．001）。结论广西煤工尘肺患病率以烟煤矿最高,无烟煤矿次之,褐煤矿最低。不同煤质煤矿尘肺患病率差异除了与粉尘浓度和游离二氧化硅含量有关外,还可能有其它影响因素。研究结果提示,在今后修订煤尘卫生标准时,可能需要根据不同的煤质制订相应的卫生标准。     

Urinary levels of proteins and metabolites in workers exposed to toluene

Summary We measured urinary excretion of albumin and retinol-binding proteins to investigate the occurrence of early renal dysfunction in 45 paint workers exposed principally to toluene, and in the same number of unexposed control subjects matched individually for sex and age. Two biological indicators of personal toluene absorption, namely urine hippuric acid and o-cresol, were also measured in the exposed subjects. A significantly higher level and increased prevalence of elevated retinol-binding protein in the urine of exposed workers was found, whereas no significant difference in urinary albumin concentration was seen between the two groups. Urinary concentrations of retinol-binding protein was correlated (r = 0.399, P < 0.006) with that of o-cresol, but not with hippuric acid or employment duration. The results suggest a dose-dependent early tubular effect due to toluene exposure that might be useful for monitoring individuals exposed to toluene at work.     

Urinary levels of proteins and metabolites in workers exposed to toluene

We measured urinary excretion of albumin and retinol-binding proteins to investigate the occurrence of early renal dysfunction in 45 paint workers exposed principally to toluene, and in the same number of unexposed control subjects matched individually for sex and age. Two biological indicators of personal toluene absorption, namely urine hippuric acid and o-cresol, were also measured in the exposed subjects. A significantly higher level and increased prevalence of elevated retinol-binding protein in the urine of exposed workers was found, whereas no significant difference in urinary albumin concentration was seen between the two groups. Urinary concentrations of retinol-binding protein was correlated (r = 0.399, P less than 0.006) with that of o-cresol, but not with hippuric acid or employment duration. The results suggest a dose-dependent early tubular effect due to toluene exposure that might be useful for monitoring individuals exposed to toluene at work.     

Chromosome studies in human subjects chronically exposed to arsenic in drinking water

A two-year study was carried out on human subjects of various ages and backgrounds who had been drinking water containing more than 0.05 mg/liter (0.05 ppm) arsenic for a period of at least five years. The main aim was to correlate the frequency of chromosome aberrations and sister chromatid exchanges in the lymphocytes with the amount of arsenic in the water. In addition, we explored the incidence of skin cancer, fetal wastage, and genetic or developmental abnormalities. Several other variables—eg, coffee, wine, and cigarette consumption; sex, residence (rural vs urban); and exposure to chemicals, smelters, or pesticides—were also taken into consideration. The data on chromosome aberrations (104 exposed and 86 control individuals) and on sister chromatid exchanges (98 exposed and 83 control individuals) did not show that arsenic at concentrations used by our population (>0.05 mg/liter) has any effect on these parameters. Similarly, no other health effects of arsenic at these concentrations were found.     

渔村与砷暴露地区居民尿砷代谢产物检测比较

目的 测定渔村居民和饮水型砷暴露地区人群尿中各种形态砷和尿总砷(TAs)。方法 选取饮水型砷暴露地区〔口肯板村水砷浓度为0.16 mg/L;乃莫板村水砷浓度为0.09 mg/L;塔布塞村(对照组)饮用水砷浓度<0.01 mg/L〕和渔村居民。采用氢化物发生原子吸收分光光度法检测尿中各形态砷代谢物和TAs含量。结果 TAs含量渔村居民明显低于0.16 mg/L暴露组,高于对照组(P<0.05),与0.09 mg/L暴露组差异无统计学意义;渔村居民尿无机砷(iAs)含量明显低于0.09和0.16 mg/L暴露组(P<0.05);尿甲基砷(MMA)含量同尿二甲基砷(DMA)含量,各组之间差异均有统计学意义(P<0.05);渔村居民尿iAs百分比明显低于对照组、0.09和0.16 mg/L暴露组(P<0.05);尿MMA百分比同尿iAs百分比;各组尿DMA百分比差异均有统计学意义(P<0.05);渔村居民特异性的检测出尿三甲胺(TMA)。结论 人群尿总砷水平受食用海产品等因素影响,不能单独作为砷暴露指标,应使用分析性方法来区分砷复合物中无机砷和有机砷的代谢产物。     

Urinary porphyrins in patients with endemic chronic arsenic poisoning caused by burning coal in China

Objective  To evaluate the effect of arsenic (As) on the porphyrin biosynthetic pathway, urine samples from patients with endemic chronic arsenic poisoning were examined. Subjects and Methods  The subjects were 16 patients, who had been exposed to As from burning coal for 8 to 25 years, and 16 controls living in the same region in Guizhou Province in southwest China. Concentrations of urinary As, porphyrins and ALA were determined by induced coupled plasma mass spectrometry (ICP-MS), high performance liquid chromatography (HPLC) with a reversed-phase column and fluorescence detector, and colorimetric spectrophotometry, respectively. Results  Concentrations of As in patients and controls, 184.40±200.04 and 86.82±64.20μ g/g creatinine (mean ±SD) respectively, were significantly different (p<0.05). The concentrations of various kinds of urinary porphyrins, including isomers I and III of coproporphyrin and pentacarboxylporphyrin, were determined. Positive correlations were observed between As and porphyrins (e.g. total porphyrins, hexacarboxylporphyrin and coproporphyrin III) or between As and ALA in male and female patients. However, porphyrin and ALA concentrations were not significantly different between the patients and the controls. Urinary porphyrin concentrations in females were higher than those in males. Conclusion  Exposure to As from burning coal may influence porphyrin biosynthesis.     

Total arsenic accumulation in yabbies (Cherax destructor Clark) exposed to elevated arsenic levels in Victorian gold mining areas, Australia

Arsenic is a proven carcinogen often found at high concentrations in association with gold and other heavy metals. The freshwater yabby, Cherax destructor Clark (Decapoda, Parastacidae), is a ubiquitous species native to Australia's central and eastern regions, with a growing international commercial market. However, in this region of Australia, yabby farmers often harvest organisms from old mine tailings dams with elevated environmental arsenic levels. Yabbies exposed to elevated environmental arsenic were found to accumulate and store as much as 100 microg/g arsenic in their tissues. The accumulation is proportional to the concentration of arsenic in the sediment and is high enough to be of concern for people who eat the yabbies. A comparison of arsenic levels in wild and lab-fed animals also was performed. Although there was no significant difference in the level of arsenic in the various organs of the wild animals, the animals purchased from a yabby farm showed a significantly higher arsenic concentration in their hepatopancreas (3.7 +/- 0.9 microg/g) compared to other organs (0.6-1.8 microg/g). Furthermore, after a 40-d exposure to food containing 200 to 300 microg/g inorganic arsenic, arsenate (As[V])-exposed animals showed a significant increase in tissue-specific arsenic accumulation, whereas arsenite (As[III])-exposed animals showed a lower, nonsignificant increase in As uptake, primarily in the hepatopancreas. These results have important implications for yabby growers and consumers alike.     

Urinary pyrethroid metabolites among pregnant women in an agricultural area of the Province of Jiangsu, China

Pyrethroid pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Of particular concern is exposure of pregnant women and their fetuses because little is known about the potential developmental hazards of such exposure. Several studies have detected internal pyrethroid exposure in urine both in adults and children, but few published data are available on metabolites in pregnant women. The present paper provides data on pyrethroid pesticides exposure based on questionnaire items and measurement of maternal urinary metabolite levels among 1149 pregnant women living in agricultural area of Jiangsu Province, China in 2009-2010, none of which reported occupational exposure to pyrethroid insecticides during pregnancy. To assess exposure to pyrethroid pesticides, urine specimens were analyzed for three main metabolites of 3-phenoxybenzoic acid (3-PBA), cis-and-trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans-DCCA) using a gas chromatography-mass spectrometry method. The limits of detection for three pyrethroid metabolites were 0.1μg/L. All pyrethroid metabolites were found in more than 94.0% of the urine samples. Median unadjusted and creatinine-adjusted values for urinary pyrethroid metabolites in these females were 1.01μg/L and 1.55μg/g Cre for 3-PBA, 0.44μg/L and 0.69μg/g Cre for cis-DCCA, 1.17μg/L and 1.86μg/g Cre for trans-DCCA, respectively. About half (45.5%) of women reported that they or family members had applied commercially available indoor insecticides during pregnancy. Both the questionnaire and laboratory data revealed that exposure to pyrethroid pesticides was considerably widespread in our subjects. The median values of urinary metabolites in the present study were about 4-10 times higher as those of general population from the developed countries. Interestingly, we found there was a temporal season variation tendency in different months. Especially, the levels of urinary metabolites in summer were significant higher than those in winter. These data indicated the need to assess the potential adverse effects of pyrethroid pesticides exposure on fetuses and infants in order to take adequate measures to protect pregnant women from pesticide exposures during pregnancy.     

Identification of urinary metabolites of human subjects exposed too-dichlorobenzene

o-Dichlorobenzene (o-DCB) has adverse effects on the liver and kidney in animals. It also causes some irritation to the eyes and the upper respiratory system in humans. This study aimed to identify urinary metabolites of human subjects exposed too-DCB. Urine samples were collected from three male workers exposed too-DCB and were analyzed using a gas chromatograph-mass spectrometer. 2,3- and 3,4-dichlorophenols and 3,4- and 4,5-dichlorocatechols were detected in the all samples. Some amounts of the four metabolites were presumably present as conjugates, because they increased after heating with hydrochloric acid.     

A follow-up study of mortality among the arseniasis patients exposed to indoor combustion of high arsenic coal in Southwest Guizhou Autonomous Prefecture, China

Objective This study was directed to ascertain the mortality of a group of arseniasis patients in an endemic rural township in Southwest China, where the residents were exposed for decades to indoor combustion of high arsenic coal. Methods All the diagnosed arseniasis cases registered in 1991 were defined as the target population, which were assigned to three symptom subgroups by the severity of dermal lesions. The death cases were surveyed and checked. The follow-up period was 12.5 years. The standardized mortality ratio (SMR) of all death causes combined, all cancers combined, and the cancers at every site were analyzed. The age standardized mortality rates (ASMRs) were calculated in three subgroups using the procedure of standardization. Results One hundred and six death cases were recorded. Liver cirrhosis, non-melanotic skin cancer, lung and liver cancer were the four most prevalent death causes and referred to 70.8% (75/106) of the total death cases. The mortality of all death causes combined was not higher than that of the whole of China in 2001 (SMR = 0.76, 95% CI 0.63–0.93). The crude mortality rate of non-melanotic skin cancer in males reached up to 128.66/10⁵. SMRs of lung cancer and larynx cancer in males (SMRs 2.84 and 27.27, 95% CIs 1.51–4.86 and 5.61–79.62, respectively) significantly exceeded the levels for all male Chinese. ASMRs of all death causes combined, all cancers combined and non-melanotic skin cancer in males of the severe dermal symptoms subgroup were significantly higher than those in medium and/or mild dermal symptom subgroups. Conclusions A significantly increased mortality due to lung cancer and non-melanotic skin cancer was confirmed, alike the situation in other arseniasis endemic areas in the world. No significant elevation of mortality due to liver cancer and bladder cancer was observed. Male arseniasis patients diagnosed with severe skin lesions face higher risks of malignancies and of non-melanotic skin cancer in particular in the following years.     

有色金属矿区非职业接触人群尿砷含量分析

目的了解贵州省赫章县长期矿山开采重金属污染地区人群尿砷含量特征。方法在开采污染最严重的妈姑镇和无矿山开采的撒拉溪镇随机选取>45岁村民作为研究对象,采集村民的尿液进行砷含量检测。结果妈姑镇男女尿砷均值分别为46.97和56.30μg/gCr,撒拉溪镇男女尿砷均值分别为36.55和45.83μg/gCr,妈姑镇人群尿砷含量高于撒拉溪镇,女性尿砷含量高于男性。妈姑镇非职业人群尿砷95%上限男女分别为99.40和141.92μg/gCr,撒拉溪镇非职业人群尿砷95%上限男女分别为65.70μg/gCr和78.06μg/gCr。结论调查地区95%村民尿砷<100μg/gCr,无慢性砷中毒。     

环境砷污染对人体健康影响的研究进展

  目的  从细胞自噬角度探讨亚慢性砷暴露对大鼠肝脏自噬作用的影响及相关分子机制。  方法  40只150～180 g SD大鼠,随机分为对照组、砷暴露高、中、低剂量组（NaAsO₂ 8、4、2 mg/kg）;灌胃给予不同浓度的含砷水,对照组给予等量生理盐水,连续12周,每周6 d。12周后处死大鼠取肝组织与全血。苏木素 – 伊红染色（HE）法观察大鼠肝脏病理变化;透射电子显微镜观察大鼠肝脏细胞超微形态;生化法检测血清谷丙转氨酶（ALT）与谷草转氨酶（AST）含量;Western blot法检测自噬相关蛋白微管轻链蛋白 – 3（LC3）、P62/sequestosome-1（SQSTM1）、哺乳动物雷帕霉素靶点（mTOR）、磷脂酰肌醇3 – 激酶（PI3K）、beclin 1（BECN 1）蛋白表达。  结果  HE染色结果显示,砷暴露可造成肝组织病理损害,其损伤程度呈剂量依赖性;肝组织的超微结构可见砷暴露组大鼠肝脏双层膜自噬小体与自噬空泡明显增多;与对照组比较,高剂量NaAsO₂组ALT、AST [分别为（98.68 ± 22.46）、（125.00 ± 13.34）U/L]活力上升（P < 0.05）;与对照组[LC3-II/LC3-I（1.03 ± 0.02）、P62（1.36 ± 0.29）、beclin 1（1.27 ± 0.13）、PI3K（0.96 ± 0.037）、mTOR（0.97 ± 0.05）]比较,NaAsO₂ 高、中剂量组大鼠肝脏中LC3-II/LC3-I比值[（1.63 ± 0.11）、（2.91 ± 0.05）]升高,beclin 1蛋白表达[（0.84 ± 0.27）、（0.98 ± 0.10）]与mTOR蛋白表达[（0.49 ± 0.02）、（0.56 ± 0.11）]下降（P < 0.05）,高、中、低剂量NaAsO₂组大鼠肝脏中P62蛋白表达[分别为（0.32 ± 0.05）、（0.13 ± 0.01）、（0.34 ± 0.05）]均下降（P < 0.05）。  结论  NaAsO₂暴露可诱导大鼠肝脏细胞自噬的发生,其机制可能与调控PI3K/mTOR信号通路有关。     

Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China

Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.     

Urinary excretion of catechin metabolites by human subjects after red wine consumption

Little is known about flavonoid metabolism and excretion in man. In the present study, the urinary excretion of a major flavonoid in wine, catechin, and its metabolites, were measured after nine human subjects each consumed 120 ml red wine (RW) on one day and de-alcoholized red wine (DRW) on a separate day. Both the RW and DRW contained 120 (SEM 3) micromol catechin (35 mg). GC-MS analyses of the trimethylsilylated derivatives of catechin and 3' and 4' methylcatechin were performed before and after hydrolysis of conjugates by beta-glucuronidase and sulfatase. Baseline urine samples collected prior to wine consumption contained 0.013 (SEM 0.005) micromol catechin and metabolites. During the 8 h period following consumption of RW and DRW, 6.6 (SEM 0.9) and 5.3 (SEM 0.6) micromol catechin and metabolites were excreted in 893 (SEM 94) and 740 (SEM 101) ml urine respectively. This corresponded to 3.0-10.3% of the dose after RW and 2.1-8.2% of the dose after DRW. The amount of catechin and metabolites excreted in urine was 20% higher after RW compared with DRW (P=0.06). Catechin in all urine samples was present as metabolites and there were no differences in the proportions of individual metabolites after RW and DRW. As with other flavonoids, the fate of most ingested catechin is not yet known.     

2013—2015年陕西居民日常膳食总砷暴露量评估及健康风险评价

目的了解陕西省居民日常总砷摄入量及评价其对人体潜在危害。方法对2013—2015年陕西省9大类4287份食品中的总砷含量进行分析,将居民经日常膳食所致总砷的暴露量与食品添加剂专家委员会(JECFA)制定的无机砷暂定每周可耐受摄入量(PTWI)进行比较,应用美国环保局推荐的健康风险评价模型对其引起的健康风险进行评价。结果陕西地区谷物和蔬菜中总砷平均含量分别为0.0265和0.0271 mg/kg,两者对居民日常总膳食中总砷暴露量的贡献率约为80%;陕西居民日常膳食所致总砷平均暴露量和偏高暴露量分别为0.423和1.10μg/(kg·d),均低于JECFA制定的无机砷暂定可耐受摄入量2.14μg/(kg·d),但其所引起的平均个人年风险值分别为9.03×10~(-5)/年和2.34×10~(-4)/年,高于国际放射防护委员会(ICRP)推荐的标准5.0×10~(-5)/年。结论陕西地区居民总砷的暴露量在安全范围内,但其引起的健康风险值却高于标准值。