Trichloroacetic acid as a biomarker of exposure to disinfection by-products in drinking water: a human exposure trial in Adelaide,Australia

We addressed the need for a biomarker of ingestion exposure to drinking water disinfection by-products by performing a human exposure trial. We evaluated urinary excretion of trichloroacetic acid (TCAA) as an exposure biomarker using 10 volunteers who normally consume their domestic tap water. We recruited the volunteers at a water quality research laboratory in Adelaide, Australia. Participants maintained a detailed consumption and exposure diary over the 5-week study. We also analyzed tap water and first morning urine (FMU) samples for TCAA, and tap water for chloral hydrate (CH). We documented both interindividual and intraindividual variability in TCAA ingestion and urinary excretion, and both were substantial. With a TCAA-free bottled water intervention, we used creatinine-adjusted urinary TCAA levels to estimate urinary TCAA excretion half-lives for three of the participants. We observed correspondence over time between estimated TCAA excretion, calculated from TCAA + CH ingestion levels, and measured TCAA urinary excretion. This study demonstrates the merits and feasibility of using TCAA in FMU as an exposure biomarker, and reveals remaining concerns about possible alternate sources of TCAA exposure for individuals with low drinking water ingestion exposure.     

Urinary excretion half life of trichloroacetic acid as a biomarker of exposure to chlorinated drinking water disinfection by-products

Methods: A longitudinal pilot exposure/intervention study measured the elimination half life of TCAA in urine. Beverage consumption was limited to a public water supply and bottled water of known TCAA concentration, and ingestion volume was managed. The five participants limited fluid consumption to only the water provided. Consumption journals were kept by each participant and their daily first morning urine (FMU) samples were analysed for TCAA and creatinine. TCAA elimination half life curves were generated from a two week washout period using TCAA-free bottled water.

Results: Individual elimination half lives ranged from 2.1 to 6.3 days, for single compartment exponential decay, the model which fit the data.

Conclusion: Urinary TCAA is persistent enough to be viable as a biomarker of medium term (days) exposure to drinking water TCAA ingestion within a range of realistic concentrations.

     

Exposure estimates to disinfection by-products of chlorinated drinking water.

Exposure to disinfection by-products (DBPs) of drinking water is multiroute and occurs in households serviced by municipal water treatment facilities that disinfect the water as a necessary step to halt the spread of waterborne infectious diseases. Biomarkers of the two most abundant groups of DBPs of chlorination, exhaled breath levels of trihalomethanes (THMs) and urinary levels of two haloacetic acids, were compared to exposure estimates calculated from in-home tap water concentrations and responses to a questionnaire related to water usage. Background THM breath concentrations were uniformly low. Strong relationships were identified between the THM breath concentrations collected after a shower and both the THM water concentration and the THM exposure from a shower, after adjusting for the postshower delay time in collecting the breath sample. Urinary haloacetic acid excretion rates were not correlated to water concentrations. Urinary trichloroacetic acid excretion rates were correlated with ingestion exposure, and that correlation was stronger in a subset of individuals who consumed beverages primarily within their home where the concentration measurements were made. No correlation was observed between an average 48-hr exposure estimate and the urinary dichloroacetic acid excretion rate, presumably because of its short biological half-life. Valid biomarkers were identified for DBP exposures, but the time between the exposure and sample collection should be considered to account for different metabolic rates among the DBPs. Further, using water concentration as an exposure estimate can introduce misclassification of exposure for DBPs whose primary route is ingestion due to the great variability in the amount of water ingested across a population.     

Urinary trichloroacetic acid levels and semen quality: A hospital-based cross-sectional study in Wuhan, China

Toxicological studies indicate an association between exposure to disinfection by-products (DBPs) and impaired male reproductive health in animals. However, epidemiological evidence in humans is still limited. We conducted a hospital-based cross-sectional study to investigate the effect of exposure to DBPs on semen quality in humans. Between May 2008 and July 2008, we recruited 418 male partners in sub-fertile couples seeking infertility medical instruction or assisted reproduction services from the Tongji Hospital in Wuhan, China. Major semen parameters analyzed included sperm concentration, motility, and morphology. Exposure to DBPs was estimated by their urinary creatinine-adjusted trichloroacetic (TCAA) concentrations that were measured with the gas chromatography/electron capture detection method. We used linear regression to assess the relationship between exposure to DBPs and semen quality. According to the World Health Organization criteria (<20 million/mL for sperm concentration and <50% motile for sperm motility) and threshold value recommended by Guzick (<9% for sperm morphology), there were 265 men with all parameters at or above the reference values, 33 men below the reference sperm concentration, 151 men below the reference sperm motility, and 6 men below the reference sperm morphology. The mean (median) urinary creatinine-adjusted TCAA concentration was 9.2 (5.1) μg/g creatinine. Linear regression analyses indicated no significant association of sperm concentration, sperm count, and sperm morphology with urinary TCAA levels. Compared with those in the lowest quartile of creatinine-adjusted urinary TCAA concentrations, subjects in the second and third quartiles had a decrease of 5.1% (95% CI: 0.6%, 9.7%) and 4.7% (95% CI: 0.2%, 9.2%) in percent motility, respectively. However, these associations were not significant after adjustment for age, abstinence time, and smoking status. The present study provides suggestive but inconclusive evidence of the relationship between decreased sperm motility and increased urinary TCAA levels. The effect of exposure to DBPs on human male reproductive health in Chinese populations still warrants further investigations.     

Drinking-Water Disinfection By-products and Semen Quality: A Cross-Sectional Study in China

Background: Exposure to disinfection by-products (DBPs) has been demonstrated to impair male reproductive health in animals, but human evidence is limited and inconsistent.Objective: We examined the association between exposure to drinking-water DBPs and semen quality in a Chinese population.Methods: We recruited 2,009 men seeking semen analysis from the Reproductive Center of Tongji Hospital in Wuhan, China, between April 2011 and May 2012. Each man provided a semen sample and a urine sample. Semen samples were analyzed for sperm concentration, sperm motility, and sperm count. As a biomarker of exposure to drinking-water DBPs, trichloroacetic acid (TCAA) was measured in the urine samples.Results: The mean (median) urinary TCAA concentration was 9.58 (7.97) μg/L (interquartile range, 6.01–10.96 μg/L). Compared with men with urine TCAA in the lowest quartile, increased adjusted odds ratios (ORs) were estimated for below-reference sperm concentration in men with TCAA in the second and fourth quartiles (OR = 1.79; 95% CI: 1.19, 2.69 and OR = 1.51; 95% CI: 0.98, 2.31, respectively), for below-reference sperm motility in men with TCAA in the second and third quartiles (OR = 1.46; 95% CI: 1.12, 1.90 and OR = 1.30; 95% CI: 1.00, 1.70, respectively), and for below-reference sperm count in men with TCAA in the second quartile (OR 1.62; 95% CI: 1.04, 2.55). Nonmonotonic associations with TCAA quartiles were also estimated for semen parameters modeled as continuous outcomes, although significant negative associations were estimated for all quartiles above the reference level for sperm motility.Conclusion: Our findings suggest that exposure to drinking-water DBPs may contribute to decreased semen quality in humans.Citation: Zeng Q, Wang YX, Xie SH, Xu L, Chen YZ, Li M, Yue J, Li YF, Liu AL, Lu WQ. 2014. Drinking-water disinfection by-products and semen quality: a cross-sectional study in China. Environ Health Perspect 122:741–746; http://dx.doi.org/10.1289/ehp.1307067     

南昌市主城区饮用水中消毒副产物含量及其健康风险评价

目的 了解南昌市主城区饮用水中消毒副产物种类、分布,并评价其潜在健康风险。方法 于 2015年枯水期（11月）、2016年丰水期（6月）采集南昌市主城区 8家市政出厂水水样 16份 ,依据《生活饮用水标准检验方法》（GB/T5750 - 2006）检测水样中 13种消毒副产物含量;运用美国环保局健康风险评价模型评价消毒副产物通过饮水途径引起的健康风险。结果 出厂水中消毒副产物浓度均符合《生活饮用水卫生标准》（GB5749 - 2006）,卤乙酸（二氯乙酸、三氯乙酸）和三卤甲烷（三氯甲烷、二溴一氯甲烷）是南昌市主城区饮用水中主要消毒副产物。消毒副产物在丰水期浓度是枯水期浓度的4.16倍,丰水期二氯乙酸、三氯乙酸、三氯甲烷浓度高于枯水期,枯水期二溴一氯甲烷浓度高于丰水期（均P＜0.05）。消毒副产物引起的致癌风险为2.83×10 - 5/年～7.98×10 - 5/年,中值5.91×10 - 5/年,非致癌风险为6.21×10 - 2/年～1.86×10 - 1/年,中值为1.22×10 - 1/年。致癌风险主要来自二氯乙酸、三氯乙酸和二氯一溴甲烷,丰水期以三氯乙酸和三氯甲烷贡献最大;枯水期以二溴一氯甲烷和二氯一溴甲烷贡献最大;而二氯乙酸对非致癌风险贡献最大。结论 卤乙酸和三卤甲烷是南昌市主城区饮用水中的主要消毒副产物,出厂水中消毒副产物引起的致癌风险在可接受的范围,但需提出风险控制措施,丰水期消毒副产物浓度应该得到控制。     

Household exposures to drinking water disinfection by-products: whole blood trihalomethane levels

Exposure to drinking water disinfection by-products (DBPs), such as trihalomethanes (THMs), has been associated with bladder and colorectal cancer in humans. Exposure to DBPs has typically been determined by examining historical water treatment records and reconstructing study participants' water consumption histories. However, other exposure routes, such as dermal absorption and inhalation, may be important components of an individual's total exposure to drinking water DBPs. In this study, we examined individuals' exposure to THMs through drinking, showering, or bathing in tap water. Thirty-one adult volunteers showered with tap water for 10 min (n = 11), bathed for 10 min in a bathtub filled with tap water (n = 10), or drank 1 l of tap water during a 10 min time period (n = 10). Participants provided three 10 ml blood samples: one sample immediately before the exposure; one sample 10 min after the exposure ended; and one sample 30 min (for shower and tub exposure) or 1 h ( for ingestion) after the exposure ended. A sample of the water (from the tap, from the bath, or from the shower) was collected for each participant. We analyzed water samples and whole blood for THMs (bromoform, bromodichloromethane, dibromochloromethane, and chloroform) using a purge-and-trap/gas chromatography/mass spectrometry method with detection limits in the parts-per-quadrillion range. The highest levels of THMs were found in the blood samples from people who took 10 min showers, whereas the lowest levels were found in the blood samples from people who drank 1 l of water in 10 min. The results from this study indicate that household activities such as bathing and showering are important routes for human exposure to THMs.     

Toxicokinetic modelling of methyl formate exposure and implications for biological monitoring

A toxicokinetic (TK) model was developed to describe the inhalation exposure in humans to methyl formate (MF), a catalyst used in foundries, and to discuss biological monitoring. The TK model consisted of four compartments: MF, the metabolites – methanol (MeOH) and formic acid (FA) – and, in addition, a urinary compartment describing the saturable reabsorption of FA. Levels of MeOH and FA in urine, from an experimental study (100 ppm MF, 8 h at rest), validated the present model. The TK model describes well the general behaviour of MeOH and FA in urine after MF exposure. A nonlinear and a linear relationship respectively, was predicted between MF exposure and FA or MeOH excretion in urine, and this has previously been seen after occupational MF exposure. The present model has been modified to simulate MeOH exposure as well. Generally low exposures (concentration or exercise) produce only marginal increases in FA urinary excretions, but when exposure is elevated, urinary FA excretion increases because of saturation in the mechanism of reabsorption. Using FA urinary excretion as the critical indicator, because of its link to health effects, an occupational exposure limit value for MF of no greater than 50 ppm should be selected (based on predictions with the TK model). MeOH in urine can be considered as a biomarker for MF at low exposure, because of lower background values and of a linear relationship with exposure. At higher exposures, however, FA could be used as a biomarker as it becomes progressively more sensitive. But the use of biological monitoring for MF is difficult because of individual variations in background values. Under the present state of knowledge both FA and MeOH should be used to estimate only group exposures, rather than individual exposures. Received: 13 December 1999 / Accepted: 25 April 2000     

Evaluation of urinary biomarkers of exposure to benzene: correlation with blood benzene and influence of confounding factors

Purpose   trans,trans-Muconic acid (t,t-MA) is generally considered as a useful biomarker of exposure to benzene. However, because of its lack of specificity, concerns about its value at low level of exposure have recently been raised. The aim of this study was (a) to compare t,t-MA, S-phenylmercapturic acid (SPMA) and benzene (B-U) as urinary biomarkers of exposure to low levels of benzene in petrochemical workers and, (b) to evaluate the influence of sorbic acid (SA) and genetic polymorphisms of biotransformation enzymes on the excretion of these biomarkers. Method  A total of 110 workers (including 24 smokers; 2–10 cigarettes/day) accepted to take part in the study. To assess external exposure to benzene, air samples were collected during the whole working period by a passive sampling device attached close to the breathing zone of 98 workers. Benzene was measured in blood (B-B) samples taken at the end of the shift, and was considered as the reference marker of internal dose. Urine was collected at the end of the shift for the determination of B-U, SPMA, t,t-MA, SA and creatinine (cr). B-U and B-B were determined by head-space/GC–MS, SPMA and SA by LC-MS, t,t-MA by HPLC-UV. Results  Most (89%) personal measurements of airborne benzene were below the limit of detection (0.1 ppm); B-B ranged from <0.10 to 13.58 μg/l (median 0.405 μg/l). The median (range) concentrations of the urinary biomarkers were as follows: B-U 0.27 μg/l (<0.10–5.35), t,t-MA 0.060 mg/l (<0.02–0.92), SPMA 1.40 μg/l (0.20–14.70). Urinary SA concentrations ranged between <3 and 2,211 μg/l (median 28.00). Benzene concentration in blood and in urine as well as SPMA, but not t,t-MA, were significantly higher in smokers than in non-smokers. The best correlation between B-B and urinary biomarkers of exposure were obtained with benzene in urine (μg/l r = 0.514, P < 0.001; μg/g cr r = 0.478, P < 0.001) and SPMA (μg/l r = 0.495, P < 0.001; μg/g cr r = 0.426, P < 0.001) followed by t,t-MA (mg/l r = 0.363, P < 0.001; mg/g cr r = 0.300, P = 0.002). SA and t,t-MA were highly correlated (r = 0.618, P < 0.001; corrected for cr r = 0.637). Multiple linear regression showed that the variation of t,t-MA was mostly explained by SA concentration in urine (30% of the explained variance) and by B-B (12%). Variations of SPMA and B-U were explained for 18 and 29%, respectively, by B-B. About 30% of the variance of B-U and SPMA were explained by B-B and smoking status. Genetic polymorphisms for biotransformation enzymes (CYP2E1, EPHX1, GSTM1, GSTT1, GSTP1) did not significantly influence the urinary concentration of any of the three urinary biomarkers at this low level of exposure. Conclusion  At low levels of benzene exposure (<0.1 ppm), (1) t,t-MA is definitely not a reliable biomarker of benzene exposure because of the clear influence of SA originating from food, (2) SPMA and B-U reflect the internal dose with almost similar accuracies, (3) genetically based inter-individual variability in urinary excretion of biomarkers seems negligible. It remains to assess which biomarker is the best predictor of health effects.     

trans,trans-Muconic acid as a biomarker of non-occupational environmental exposure to benzene

 Excretion of trans,trans-muconic acid (2,4-hexadienedioic acid; t,t-MA), a potential biomarker of low-level exposure to benzene, was determined in 32 smokers and 82 nonsmokers. In smokers the median background excretion of t,t-MA was 0.13 (0.06–0.39) mg/g creatinine and was significantly higher (P<0.05) than the value of 0.065 (0.02–0.59) mg/g creatinine in nonsmokers. For nonsmokers, the correlation between t,t-MA excretion and environmental exposure to benzene in ambient air, which was determined during the 8-day study period by personal diffusion samplers, was not significant (r=0.164, P=0.18). Nonsmokers living in the city tended to have higher t,t-MA excretion rates than nonsmokers living in the suburbs. However, the difference was only significant for nonsmokers from nonsmoking homes. For the same location (suburb or city), smoking at home leads to a marginal increase in t,t-MA excretion of the nonsmoking members of the household. In a further study with eight nonsmokers we found that dietary supplementation with 500 mg sorbic acid significantly increased (P<0.001) the mean urinary t,t-MA excretion from 0.08 (0.04–0.12) to 0.88 (0.57–1.48) mg/24 h. Under study conditions 0.12% of the sorbic acid dose was excreted in urine as t,t-MA, thereby indicating that a typical dietary intake of 6–30 mg/day sorbic acid accounts for 10–50% of the background t,t-MA excretion in nonsmokers, and for 5–25% in smokers. As a consequence, sorbic acid in the diet is a significant confounding factor in assessing low-level benzene exposure if t,t-MA excretion in urine is used as a biomarker. Received: 10 October 1995 / Accepted: 26 February 1996     

Renal effects of uranium in drinking water

Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L.     

Environmental and urinary markers of prenatal exposure to drinking water disinfection by-products, fetal growth, and duration of gestation in the PELAGIE birth cohort (Brittany, France, 2002-2006)

Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation, its impact on fetal growth remains an open question. The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction (FGR) and preterm birth in the PELAGIE cohort, a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006. Exposure was assessed by estimating levels of trihalomethanes (THMs) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid (TCAA) during early pregnancy in a nested case-control design that compared 174 FGR cases, 114 preterm births, and 399 controls. Higher uptake of THMs (especially brominated THMs) was associated with a higher risk of FGR. Women with TCAA detected in their urine (>0.01 mg/L) had a higher risk of FGR than those with TCAA levels below the detection limit (adjusted odds ratio = 1.8, 95% confidence interval: 0.9, 3.7) and had an odds ratio for preterm birth below 1 (adjusted odds ratio = 0.8, 95% confidence interval: 0.3, 2.6). Results from this prospective study, the first to use a biomarker of disinfection by-product exposure, suggest that prenatal exposure affects fetal growth, but the causal agent or agents remain to be identified.     

Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico

The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 microg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r = 0.50, P < 0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 microg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 microg/L, and it was statistically significantly different from those of the other towns (P < 0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations.     

Effects of orange juice and proline betaine on glycine betaine and homocysteine in healthy male subjects

Background Proline betaine (PB), a glycine betaine (GB) analogue found in citrus foods, increases urinary GB loss and plasma total homocysteine (tHcy) concentrations in rats. Its presence in human plasma is associated with increased GB excretion. Aim To compare the effects of dietary levels of PB on GB excretion, and on plasma tHcy and GB concentrations in healthy volunteers. Methods In a randomized crossover study, eight healthy males (18–50 years) ingested either 750 mL orange juice (containing 0.545 g PB), a PB supplement (0.545 g PB dissolved in 750 mL apple juice), or 750 mL apple juice (control). Plasma PB, GB and tHcy, and urine PB, GB and creatinine concentrations were measured hourly for 6 h and at 24 h post-treatment. Results Plasma tHcy concentrations were not increased (relative to control) following ingestion of either orange juice or PB supplement. Both treatments produced a significant increase in plasma PB concentrations (P < 0.001), this effect being greater following orange juice compared with PB supplement (P < 0.05, 1–2 h). Urinary excretion of PB was greater than the control following both orange juice (P < 0.001) and PB supplement (P < 0.001), from 2 to 24 h post-treatment. This increase in PB excretion was significantly greater following orange juice compared with PB supplement with higher peak excretion (C _max difference, P = 0.008). GB excretion was significantly greater following ingestion of orange juice compared with PB in apple juice (P = 0.007) and apple juice control (P < 0.001) in the first 2 h post-ingestion. Conclusions PB administered in dietary doses had little effect on plasma tHcy concentrations in healthy humans. Ingestion of PB in orange juice compared with PB alone resulted in greater increases in the urinary excretion of PB and GB.     

Urinary excretion of total isothiocyanates from cruciferous vegetables shows high dose–response relationship and may be a useful biomarker for isothiocyanate exposure

Background Isothiocyanates (ITCs), hydrolysis products from glucosinolates, are a family of biologically active compounds originating from cruciferous vegetables. Many ITCs are assumed to have cancer preventive effects and to further evaluate these potential health effects, reliable biomarkers of ITC exposure are needed. Aim of the study In this study we investigated the ability of urinary ITC excretion to reflect a low or high daily intake of cruciferous vegetables. Methods The design was a controlled human crossover study (n = 6). Subjects consumed a self-restricted glucosinolate-free diet 48 h before the study-day where a basic diet supplemented with 80 or 350 g of mixed cruciferous vegetables was consumed. All urine was collected in intervals during the 48 h period after ingestion of the cruciferous vegetables. Total ITC in the cruciferous mixture and total ITC and their metabolites in urine was quantified as the cyclocondensation product of 1,2-bezenedithiol by high performance liquid chromatography. Results The total urinary excretion of ITCs correlated significantly with the two doses of ITC from diets with high or low cruciferous content (r _s = 0.90, P < 0.01). The fraction of urinary ITC excreted was 69.02 ± 11.57% and 74.53 ± 8.39% of the amounts ingested for 80 and 350 g cruciferous vegetables, respectively. Conclusion The results in this study indicate that the urinary excretion of ITCs, measured by use of the cyclocondesation reaction, is a useful and precise tool that may be used as a biomarker of ITC exposure in population based studies.     

Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh

Objectives

Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content.

Methods

The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry.

Results

The median iAs concentration in drinking water was 55 μgAs/L (range <0.5–332 μgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7–32.3), 1.8 (<0.5–3.3), 13.7 (5.6–25.0), and 88.6 μgAs/L (47.9–153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water.

Conclusions

All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.     

The Implications of Using a Physiologically Based Pharmacokinetic (PBPK) Model for Pesticide Risk Assessment

Background

A physiologically based pharmacokinetic (PBPK) model would make it possible to simulate the dynamics of chemical absorption, distribution, metabolism, and elimination (ADME) from different routes of exposures and, in theory, could be used to evaluate associations between exposures and biomarker measurements in blood or urine.

Objective

We used a PBPK model to predict urinary excretion of 3,5,6-trichloro-2-pyridinol (TCPY), the specific metabolite of chlorpyrifos (CPF), in young children.

Methods

We developed a child-specific PBPK model for CPF using PBPK models previously developed for rats and adult humans. Data used in the model simulation were collected from 13 children 3–6 years of age who participated in a cross-sectional pesticide exposure assessment study with repeated environmental and biological sampling.

Results

The model-predicted urinary TCPY excretion estimates were consistent with measured levels for 2 children with two 24-hr duplicate food samples that contained 350 and 12 ng/g of CPF, respectively. However, we found that the majority of model outputs underpredicted the measured urinary TCPY excretion.

Conclusions

We concluded that the potential measurement errors associated with the aggregate exposure measurements will probably limit the applicability of PBPK model estimates for interpreting urinary TCPY excretion and absorbed CPF dose from multiple sources of exposure. However, recent changes in organophosphorus (OP) use have shifted exposures from multipathways to dietary ingestion only. Thus, we concluded that the PBPK model is still a valuable tool for converting dietary pesticide exposures to absorbed dose estimates when the model input data are accurate estimates of dietary pesticide exposures.     

Exposure to inorganic arsenic in drinking water and total urinary arsenic concentration in a Chilean population

The relationship of inorganic arsenic exposure through drinking water and total urinary arsenic excretion in a nonoccupationally exposed population was evaluated in a cross-sectional study in three mayor cities of Chile (Antofagasta, Santiago, and Temuco). A total of 756 individuals in three population strata (elderly, students, and workers) provided first morning void urine specimens the day after exposure and food surveys were administered. Arsenic intake from drinking water was estimated from analysis of tap water samples, plus 24-h dietary recall and food frequency questionnaires. Multilevel analysis was used to evaluate the effects of the age group and city factors adjusted by predictor variables. Arsenic levels in drinking water and urine were significantly higher in Antofagasta compared with the other cities. City-and individual-level factors, 12% and 88%, respectively, accounted for the variability in urinary arsenic concentration. The main predictors of urinary arsenic concentration were total arsenic consumption through water and age. These findings indicate that arsenic concentration in drinking water continues to be the principal contributing factor to exposure to inorganic arsenic in the Chilean population.     

Urinary methanol and formic acid as indicators of occupational exposure to methyl formate

Objective: To evaluate the validity of methanol (MeOH) and formic acid (FA) in urine as biological indicators of methyl formate (MF) exposure in experimental and field situations. Methods: The subjects were 28 foundrymen and two groups of volunteers (20 control and 20 exposed). Exposure assessment of the workers was performed by personal air and biological monitoring. Methyl formate vapour collected on charcoal tube was analysed by gas chromatography. The concentration of MF in the exposure chamber (volunteer-study) was monitored by two independent methods [flame ionisation detection (FID) and Fourier transformation infra-red detection (FTIR)]. Urinary metabolites (MeOH and FA) were analysed separately by head-space gas chromatography. Results: The volunteers exposed to 100 ppm MF vapour at rest for 8 h excreted 3.62 ± 1.13 mg MeOH/l (mean ± SD) at the end of the exposure. This was statistically different (P < 0.001) from pre-exposure MeOH excretion (2.15 ± 0.80 mg/l), or from that of controls (1.69 ± 0.48 mg/l). The urinary FA excretion was 32.2 ± 11.3 mg/g creatinine after the exposure, which was statistically different (P < 0.001) from pre-exposure excretion (18.0 ± 9.3 mg/g creatinine) or that of controls (13.8 ± 7.9 mg/g creatinine). In foundrymen, the urinary FA excretion after the 8 h workshift exposure to a time weighted average (TWA) concentration of 2 to 156 ppm MF showed a dose-dependent increase best modelled by a polynomial function. The highest urinary FA concentration was 129 mg/g creatinine. The pre-shift urinary FA of the foundrymen (18.3 ± 5.6 mg/g creatinine) did not differ from that of controls (13.8 ± 7.9 mg/g creatinine). The urinary MeOH excretion of the foundrymen after the shift, varied from <1 to 15.4 mg/l, while the correlation with the preceding MF exposure was poor. The foundrymen excreted more (P=0.01) FA (2.12 ± 3.56 mg/g creatinine) after the workshift than experimentally, once-exposed volunteers (0.32 ± 0.11 mg/g creatinine) at a similar inhaled MF level of 1 ppm). Conclusions: In spite of its high background level in non-exposed subjects, urinary FA seems to be a useful biomarker of methyl formate exposure. The question remains as to what is the reason for the differences in chronic and acute exposure respectively. Received: 27 September 1999 / Accepted: 25 March 2000     

Rainfall and outbreaks of drinking water related disease and in England and Wales

A case-crossover study compared rainfall in the 4 weeks before drinking water related outbreaks with that in the five previous control years. This included public and private drinking water related outbreaks in England and Wales from 1910 to 1999. Of 111 outbreaks, 89 met inclusion criteria and the implicated pathogens included Giardia, Cryptosporidium, E. coli, S. Typhi, S. Paratyphi, Campylobacter and Streptobacillus moniliformis. Weather data was derived from the British Atmospheric Data Centre There was a significant association between excess cumulative rainfall in the previous 7 days and outbreaks (p=0.001). There was an excess of rainfall below 20 mm for the three weeks previous to this in outbreak compared to control weeks (p=0.002). Cumulative rainfall exceedances were associated with outbreak years. This study provides evidence that both low rainfall and heavy rain precede many drinking water outbreaks and assessing the health impacts of climate change should examine both.