Toluene vapor exposure and urinary excretion of hippuric acid among workers in China.

A factory survey was conducted in three provinces in China from 1985 to 1989. The time-weighted average toluene concentrations in breathing zone air were monitored by diffusive sampling, whereas hippuric acid (HA) concentrations in shift-end urine samples were measured by high performance liquid chromatography (HPLC). Exposed workers (456 men and women) were those for whom toluene (up to 548 ppm toluene) accounted for greater than or equal to 90% of total exposure (by vapor concentration in ppm), whereas 517 nonexposed controls were recruited from the same factories or from factories of the same region. There was a linear correlation between the intensity of toluene exposure and HA concentration in the shift-end urine. Comparison of the results with findings in the literature shows that the toluene-induced increase in urinary HA concentration among workers in China is significantly smaller than the published values, whereas HA concentrations in urine samples from nonexposed controls are comparable to the levels previously reported.     

Hippuric acid and ortho-cresol as biological indicators of occupational exposure to toluene

Industrial exposure to toluene was studied in a group of 18 subjects working in a printing plant, exposed only to this solvent. Environmental monitoring was carried out using personal samplers for the whole work-shift. Urine samples were collected for the determination of hippuric acid and ortho(o)-cresol before toluene exposure, at the end of the work-shift, and 5, 9, and 17 h after the end of the work-shift. The values of two metabolites in all the urinary samples were corrected for g creatinine and specific gravity (1.024). Toluene time weighted average (TWA) concentrations ranged from 51 to 221 mg/m³ (7-h samples; two samplings lasting 3.5 h each). Urinary hippuric acid and o-cresol values at the end of the work-shift were significantly higher than the prework-shift values. Both hippuricuria and o-cresoluria end-of-work-shift values, corrected for creatinine and specific gravity, were significantly related to the mean daily environmental concentration of toluene, the correlation being weaker for o-cresol. Correlation coefficients were 0.88 and 0.84 for hippuric acid and 0.63 and 0.62 for o-cresol after correction for creatinine and specific gravity, respectively. No significant relationship was observed between environmental exposure and the values of the two urinary metabolites 5, 9, and 17 h after the end of the work-shift. Extrapolated values from the linear regression analysis at 375 mg/m³ were in good agreement with the biological exposure index (BEI) suggested by ACGIH for hippuric acid. We conclude that determination of hippuric acid in urine samples collected at the end of the work-shift can be used for routine biological monitoring of exposure to toluene, even at low levels. O-cresol seems to be a less reliable indicator of toluene exposure.     

Exposure to toluene and urinary hippuric acid excretion in a group of heliorotagravure printing workers

Summary The influence of a number of factors possibly affecting the relation between urinary hippuric acid excretion and the exposure level to toluene was studied in a population of heliorotagravure printers. It was observed that the hippuric acid excretion rates, after 4 h and 8 h from the onset of the exposure, were in better agreement with the average toluene concentrations in work room air than either the urinary metabolite concentrations alone or corrected for urine density. Apart from differences in exposure level, a substantial proportion of the interindividual variability in hippuric acid excretion could be explained by differences in energetical load during the exposure. It was thereby not possible to elucidate the full extent to which this factor influences the metabolite excretion.In good agreement with previous experimental findings, the hippuric acid excretion rate apparently does not depend on the time of urine sampling during the exposure, provided that at least 4 h have elapsed from the onset.     

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     

S-phenylmercapturic acid (S-PMA) levels in urine as an indicator of exposure to benzene in the Kinshasa population

Background and objectives

Data on human exposure to chemicals in Africa are scarce. A biomonitoring study was conducted in a representative sample of the population in Kinshasa (Democratic Republic of Congo) to document exposure to benzene.

Methods

S-phenylmercapturic acid (S-PMA) was measured by LC–MS/MS in spot urine samples from 220 individuals (50.5% women), aged 6–70 years living in the urban area and from 50 additional subjects from the sub-rural area of Kinshasa. Data were compiled as arithmetic means, geometric means, percentile 95th and range expressed in μg/L.

Results

Overall, living in urban Kinshasa was associated with increased levels of S-PMA in urine as compared to a population living in the sub-rural area. Increased levels were also found by comparison with some date from literature.

Conclusions

This study reveals the high benzene exposure of the Kinshasa population requiring the determination of benzene concentrations in ambient air of Kinshasa and limit values for the protection of human health.     

Urinary excretion of hippuric acid and m- or p-methylhippuric acid in the urine of persons exposed to vapours of toluene and m- or p-xylene as a test of exposure

Ogata, M., Tomokuni, K., and Takatsuka, Y. (1970).Brit. J. industr. Med.,27, 43-50. Urinary excretion of hippuric acid and m- or p-methylhippuric acid in the urine of persons exposed to vapours of toluene and m- or p-xylene as a test of exposure. Twenty-three male volunteers were exposed in groups of four or five to toluene and m- and p-xylene vapour for periods of 3 hours or of 7 hours with one break of an hour. Urine was collected at hourly intervals for several hours, and thereafter all urine was collected until 18 hours after the end of the exposure period, and was analysed for hippuric and methylhippuric acids. It was shown that hippuric acid was excreted equivalent to 68% of the toluene absorbed, and m-methylhippuric acid equivalent to 72% of the m-xylene absorbed. Up to hydrocarbon concentrations of 200 ppm the total quantity of hippuric acids excerted was proportional to the total exposure (ppm × hours). In descending order of precision the following were also related to exposure: rate of excretion during the exposure period; concentrations of hippuric acid in urine corrected to constant urine density; and concentrations in urine uncorrected for density. The last could not be used to calculate exposure, but the others could be to give screening tests to show whether workmen could have been exposed to concentrations greater than the maximum allowable.

The effects of exposure on blood pressure, pulse rate, flicker value, and reaction time were measured. There were some variations which suggested that the MAC of toluene should be set higher than 200 ppm.

     

Quantitative analysis of urinary glycine conjugates by high performance liquid chromatography: excretion of hippuric acid and methylhippuric acids in the urine of subjects exposed to vapours of toluene and xylenes

Summary A new method for the direct determination of hippuric acid (HA) and o-, m- and p-methylhippuric acids (MHAs) in the urine, metabolites of toluene and o-, m- and p-xylenes by high performance liquid chromatography (HPLC) is described. A stainless-steel column packed with silica gel having dinitrophenyl residue and a mixed solution of methanol/water/acetic acid (80/20/0.2) containing tetra-n-butylammonium bromide (0.2% w/v) as mobile phase was used. Concentrations of HA and MHAs were estimated from their peak height at a wave length of 225 nm. Urine can be analyzed directly without solvent extraction or pretreatment to obtain complete separation of HA and o-, m- and p-MHAs. Urine samples from male workers exposed to toluene or xylenes were analyzed for HA or MHAs. The urinary levels of HA and MHAs increased by exposure to toluene and xylenes in proportion to the environmental concentrations of the solvents, although there is a considerable variation in metabolite concentrations. The slope of regression line between toluene and HA and that between m-xylene and m-MHA were similar. The urinary concentrations of HA and MHAs corresponding to 100 ppm (TLV) of toluene was 2.35 g/g creatinine and that of m-MHA corresponding to 100 ppm (TLV) of m-xylene was 2.05 g/g creatinine. The warning levels of the urinary metabolite concentrations of a group of workers and that of an individual worker corresponding to TLV of organic solvent concentration is discussed.     

Evaluation of workers' exposure to 2-ethylhexanoic acid (2-EHA) in Finnish sawmills

Summary Exposure to a new wood preservative agent (Sinesto B), whose active ingredient is 2-ethylhexanoic acid (2-EHA), was determined by urinalysis of the parent chemical and its metabolites in workers employed in four Finnish sawmills. The excretion of these chemicals was compared with the inhaled dose analyzed in air samples collected at the breathing zone and with the percutaneous absorption determined by epicutaneous sampling. The main route for entrance of 2-EHA into the body is by breathing, because the urinary concentration of 2-EHA correlated linearly with the concentration of 2-EHA in the air (r = 0.70). There was no correlation between skin contamination and urinary levels of 2-EHA. In most cases the highest urinary concentrations of 2-EHA were found immediately after the work shift. Therefore, in order to evaluate a worker's exposure, the urine sample has to be taken immediately after the work shift. Workers in cranes had the highest exposure to 2-EHA, which describes well the evaporation of Sinesto B into the ambient air. 2-EHA was not found in the urine of non-exposed workers.Supported by the Finnish Work Environment Fund, Helsinki, Finland     

A cross-sectional analysis of type II diabetes in a community with exposure to perfluorooctanoic acid (PFOA)

Background

Increased diabetes mortality has been reported in workers exposed to perfluorooctanoic acid (PFOA). We analyzed the relationships among serum PFOA, type II diabetes, and fasting glucose in a population with high levels of serum PFOA resulting from drinking contaminated water.

Methods

The study population was adults participating in a health survey in 2005-2006 (N=54,468). Subjects reported prevalent diabetes, age at diagnosis, and provided blood in which serum PFOA and glucose levels were measured. We conducted a case-control analysis restricted to long-time residents (≥20 years, N=13,922), to maximize the likelihood that serum PFOA levels in 2005 reflected previous exposure. Cases (N=1055) were restricted to those with medical record validation and at least 10-year residence prior to diagnosis. We also studied fasting glucose and serum PFOA in a subset (N=21,642).

Results

Median serum PFOA was 28 ng/ml, compared with 4 ng/ml in the general US population. Reported diabetes prevalence was 7.8%, similar to what was expected. Adjusted for confounders, all upper deciles of serum PFOA had a decreased risk of diabetes compared with the lowest (odds ratios—ORs by decile, 1.00, 0.71, 0.60, 0.72, 0.65, 0.65, 0.87, 0.58, 0.62, 0.72). There was no consistent pattern between fasting serum glucose and PFOA (glucose by decile, 94, 95, 95, 93, 94, 92, 92, 92, 92, 93, adjusted for confounders).

Conclusions

Our findings do not demonstrate an association between PFOA and either type II diabetes or fasting glucose level. Our data are limited by their cross-sectional nature, and do not preclude the possibility of a causal relationship.     

Response of tissue phospholipid fatty acid composition to dietary (n-6) and replacement with marine (n-3) and saturated fatty acids in the rat

Nine groups of weanling male rats were maintained for ten weeks on a fat-free semi-synthetic diet supplemented with 10% by weight of oil, composed wholly of gamma-linolenic acid-rich evening primrose oil, or replaced partly or completely (25%, 50%, 75%, and 100%) by marine or hydrogenated coconut oils. Plasma phospholipid content and phospholipid fatty acid composition of plasma, red blood cells, liver, kidney, and heart were determined. Replacement of marine oil as 2.5% of the diet caused a decrease of plasma phospholipid concentration to 60%, with no furthur decrease at higher proportions. Except in the heart, marine oil in combination with evening primrose oil caused an increase in 20:3(n-6) concentration, and a decrease in 20:4(n-6) levels in all tissues examined. The ratio 20:3(n-6)/20:4(n-6) increased with increasing marine oil supplementation to the diet, but not when marine oil was the sole source of dietary fatty acids (10%). Replacement of hydrogenated coconut oil did not affect 20:3(n-6) concentrations. A decrease in 20:4(n-6) was observed when hydrogenated coconut oil was supplemented to the diet at 10%, causing a state of EFA deficiency as shown by the elevation of 20:3(n-9). There was an increase in 20:5(n-3) and 22:6(n-3) with increased marine oil intake. The ratio 20:3(n-6)/20:4(n-6) correlated significantly with 20:5(n-3), but not with 22:6(n-3), in all tissues except the heart, suggesting an inhibitory effect of 20:5(n-3) on delta-5-desaturase enzyme.     

Serum uric acid correlates in elderly men and women with special reference to body composition and dietary intake (Dutch nutrition surveillance system)

In 460 apparently healthy Dutch elderly, aged 65–79 years, serum uric acid correlates were studied by linear regression analyses, for men and women separately. Diuretic therapy, total serum cholesterol (women only) and creatinine clearance (in bivariate analysis only) were significantly associated with serum uric acid level. Positive associations of serum uric acid with body weight, body mass index, body fatness (men) and lean body mass (men) were observed, with and without adjustment for diuretic therapy, creatinine clearance and age. Serum uric acid levels, whether adjusted or not for these variables and for body mass index, were positively associated with alcohol intake (men) and consumption of meat and fish (women), and inversely with consumption of bread, margarine and milk products (women). These results indicate that limited medication with diuretics, weight control and restriction of alcohol use may help to prevent hyperuricemia in the elderly.     

Private drinking water wells as a source of exposure to perfluorooctanoic acid (PFOA) in communities surrounding a fluoropolymer production facility

Background

The C8 Health Project was established in 2005 to collect data on perfluorooctanoic acid (PFOA, or C8) and human health in Ohio and West Virginia communities contaminated by a fluoropolymer production facility.

Objective

We assessed PFOA exposure via contaminated drinking water in a subset of C8 Health Project participants who drank water from private wells.

Methods

Participants provided demographic information and residential, occupational, and medical histories. Laboratory analyses were conducted to determine serum-PFOA concentrations. PFOA data were collected from 2001 through 2005 from 62 private drinking water wells. We examined the relationship between drinking water and PFOA levels in serum using robust regression methods. As a comparison with regression models, we used a first-order, single-compartment pharmacokinetic model to estimate the serum:drinking-water concentration ratio at steady state.

Results

The median serum PFOA concentration in 108 study participants who used private wells was 75.7 μg/L, approximately 20 times greater than the levels in the U.S. general population but similar to those of local residents who drank public water. Each 1 μg/L increase in PFOA levels in drinking water was associated with an increase in serum concentrations of 141.5 μg/L (95% confidence interval, 134.9–148.1). The serum:drinking-water concentration ratio for the steady-state pharmacokinetic model was 114.

Conclusions

PFOA-contaminated drinking water is a significant contributor to PFOA levels in serum in the study population. Regression methods and pharmacokinetic modeling produced similar estimates of the relationship.     

Exploring indirect sources of human exposure to perfluoroalkyl carboxylates (PFCAs): evaluating uptake, elimination, and biotransformation of polyfluoroalkyl phosphate esters (PAPs) in the rat

Background

Perfluorinated carboxylic acids (PFCAs) are ubiquitous in human sera worldwide. Biotransformation of the polyfluoroalkyl phosphate esters (PAPs) is a possible source of PFCA exposure, because PAPs are used in food-contact paper packaging and have been observed in human sera.

Objectives

We determined pharmacokinetic parameters for the PAP monoesters (monoPAPs) and PAP diesters (diPAPs), as well as biotransformation yields to the PFCAs, using a rat model.

Methods

The animals were dosed intravenously or by oral gavage with a mixture of 4:2, 6:2, 8:2, and 10:2 monoPAP or diPAP chain lengths. Concentrations of the PAPs and PFCAs, as well as metabolic intermediates and phase II metabolites, were monitored over time in blood, urine, and feces.

Results

The diPAPs were bioavailable, with bioavailability decreasing as the chain length increased from 4 to 10 perfluorinated carbons. The monoPAPs were not absorbed from the gut; however, we found evidence to suggest phosphate-ester cleavage within the gut contents. We observed biotransformation to the PFCAs for both monoPAP and diPAP congeners.

Conclusions

Using experimentally derived biotransformation yields, perfluorooctanoic acid (PFOA) sera concentrations were predicted from the biotransformation of 8:2 diPAP at concentrations observed in human serum. Because of the long human serum half-life of PFOA, biotransformation of diPAP even with low-level exposure could over time result in significant exposure to PFOA. Although humans are exposed directly to PFCAs in food and dust, the pharmacokinetic parameters determined here suggest that PAP exposure should be considered a significant indirect source of human PFCA contamination.     

Nonlinear associations between dietary exposures to perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) and type 2 diabetes risk in women: Findings from the E3N cohort study

The incidence of type 2 diabetes (T2D) is steadily rising worldwide since the past 30 years. There is increasing interest in understanding the contribution of exposure to endocrine disrupting chemicals (EDCs) to T2D trend. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are stable, persistent, and bioaccumulative synthetic compounds, suspected to act as EDCs and for which the diet is the main route of exposure. We investigated associations between estimated dietary exposure to PFOS and PFOA and the risk of T2D in the large E3N prospective cohort study.Among 71 270 women included in this study, 2680 cases of incident type 2 diabetes were validated during follow-up (1993–2012). Dietary exposure was estimated combining dietary consumption data collected in E3N and food contamination data provided by ANSES in the 2nd French Total Diet Study. The estimated mean dietary exposure to PFOS and PFOA was 0.50?ng/kg _{body weight}/day and 0.86?ng/kg _{body weight}/day respectively. An inverse U-shape association was found when considering PFOA and T2D: women in the 4th, 5th, and 6th decile groups had a HR [95%CI] of 1.21 [1.06–1.46], 1.35 [1.15–1.59], and 1.33 [1.05–1.41], respectively, when compared to women of the 1st decile group, while the other decile groups were not associated to the risk of T2D. The positive association had the strongest effect size for non-obese women (body mass index (BMI) ≤25?kg/m²). No association was found between dietary exposure to PFOS and T2D, except when considering only women with BMI≤25?kg/m2, in which a positive nonlinear association was observed (HR [95%CI]?=?1.46 [1.09–1.96], 1.52 [1.09–2.11], and 1.44 [1.01–2.06] for the 6th, 8th, and 9th decile groups respectively).This is the first study to evaluate the association between dietary exposure to PFOA and PFOS and the risk of developing T2D in a large observational study with over 15 years of follow-up. The present study highlights the importance of studying the effects of EDCs in large epidemiological studies including not occupationally exposed populations, as well as the importance of considering exposure to PFOS and PFOA as a relevant risk factor for T2D.     

Biological monitoring of workers occupationally exposed to carbon disulphide in a rayon plant in Brazil: Validity of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine samples taken in different times, during and after the real exposure period

Fifteen workers from a rayon plant in Brazil were monitored. Air samples were taken during a mean period of 5.8 hours out of an 8 hour workshift, in three different adsorbing tubes. Five urine samples were taken at 4 hour interval from the beginning of the shift, and at the beginning of the next shift in which 2-thiothiazolidine-4-carboxylic acid (TTCA) concentration was analysed. Data from seventeen individuals were statistically studied, with the aim of establishing the best and the most practical sampling strategy of biological monitoring for workers occupationally exposed to CS₂. For those chronically exposed to CS₂, TWA air concentration lower than 30 and higher than 10 mg/m³, it was found that the higher the exposure levels, the lower was TTCA concentration in the end of shift urine samples. The results may be explained by dietary habits and/or by the small number of examined population or even eventual casualty. On the other hand they raise other hypothesis involving the chronicity of exposure which may lead to important changes in metabolism influencing the excretion rate of TTCA.