Sex differences in urinary levels of several biological indicators of exposure: a simulation study using a compartmental based toxicokinetic model

Toxicokinetic modeling is a useful tool to describe or predict the behavior of a chemical agent in the human or animal organism. A general model based on four compartments was developed in a previous study in order to quantify the effect of human variability on a wide range of biological exposure indicators. The aim of this study was to adapt this existing general toxicokinetic model to three organic solvents, which were methyl ethyl ketone, 1-methoxy-2-propanol and 1,1,1,-trichloroethane, and to take into account sex differences. We assessed in a previous human volunteer study the impact of sex on different biomarkers of exposure corresponding to the three organic solvents mentioned above. Results from that study suggested that not only physiological differences between men and women but also differences due to sex hormones levels could influence the toxicokinetics of the solvents. In fact the use of hormonal contraceptive had an effect on the urinary levels of several biomarkers, suggesting that exogenous sex hormones could influence CYP2E1 enzyme activity. These experimental data were used to calibrate the toxicokinetic models developed in this study. Our results showed that it was possible to use an existing general toxicokinetic model for other compounds. In fact, most of the simulation results showed good agreement with the experimental data obtained for the studied solvents, with a percentage of model predictions that lies within the 95% confidence interval varying from 44.4 to 90%. Results pointed out that for same exposure conditions, men and women can show important differences in urinary levels of biological indicators of exposure. Moreover, when running the models by simulating industrial working conditions, these differences could even be more pronounced. In conclusion, a general and simple toxicokinetic model, adapted for three well known organic solvents, allowed us to show that metabolic parameters can have an important impact on the urinary levels of the corresponding biomarkers. These observations give evidence of an interindividual variablity, an aspect that should have its place in the approaches for setting limits of occupational exposure

ART, Stoffenmanager, and TRA: a systematic comparison of exposure estimates using the TREXMO translation system

Several occupational exposure models are recommended under the EU's REACH legislation. Due to limited availability of high-quality exposure data, their validation is an ongoing process. It was shown, however, that different models may calculate significantly different estimates and thus lead to potentially dangerous conclusions about chemical risk. In this paper, the between-model translation rules defined in TREXMO were used to generate 319000 different in silico exposure situations in ART, Stoffenmanager, and ECETOC TRA v3. The three models' estimates were computed and the correlation and consistency between them were investigated. The best correlated pair was Stoffenmanager-ART (R, 0.52-0.90), whereas the ART-TRA and Stoffenmanager-TRA correlations were either lower (R, 0.36-0.69) or no correlation was found. Consistency varied significantly according to different exposure types (e.g. vapour versus dust) or settings (near-field versus far-field and indoors versus outdoors). The percentages of generated situations for which estimates differed by more than a factor of 100 ranged from 14 to 97%, 37 to 99%, and 1 to 68% for Stoffenmanager-ART, TRA-ART, and TRA-Stoffenmanager, respectively. Overall, the models were more consistent for vapours than for dusts and solids, near-fields than for far-fields, and indoor than for outdoor exposure. Multiple linear regression analyses evidenced the relationship between the models' parameters and the relative differences between the models' predictions. The relative difference can be used to estimate the consistency between the models. Furthermore, the study showed that the tiered approach is not generally applicable to all exposure situations. These findings emphasize the need for a multiple-model approach to assessing critical exposure scenarios under REACH. Moreover, in combination with occupational exposure measurements, they might also be used for future studies to improve prediction accuracy

Beliefs and practices in the assessment of workplace pollutants

Summary.: Objectives: A survey was undertaken among Swiss occupational hygienists and other professionals to identify the different exposure assessment methods used, the contextual parameters observed and the uses, difficulties and possible developments of exposure models for field application. Methods: A questionnaire was mailed to 121 occupational hygienists, all members of the Swiss Occupational Hygiene Society. A shorter questionnaire was also sent to registered occupational physicians and selected safety specialists. Descriptive statistics and multivariate analyses were performed. Results: The response rate for occupational hygienists was 60%. The so-called expert judgement appeared to be the most widely used method, but its efficiency and reliability were both judged with very low scores. Long-term sampling was perceived as the most efficient and reliable method. Various determinants of exposure, such as emission rate and work activity, were often considered important, even though they were not included in the exposure assessment processes. Near field local phenomena determinants were also judged important for operator exposure estimation. Conclusion: Exposure models should be improved to integrate factors which are more easily accessible to practitioners. Descriptors of emission and local phenomena should also be include

A Detailed Urinary Excretion Time Course Study of Captan and Folpet Biomarkers in Workers for the Estimation of Dose, Main Route-of-Entry and Most Appropriate Sampling and Analysis Strategies

Captan and folpet are two fungicides largely used in agriculture, but biomonitoring data are mostly limited to measurements of captan metabolite concentrations in spot urine samples of workers, which complicate interpretation of results in terms of internal dose estimation, daily variations according to tasks performed, and most plausible routes of exposure. This study aimed at performing repeated biological measurements of exposure to captan and folpet in field workers (i) to better assess internal dose along with main routes-of-entry according to tasks and (ii) to establish most appropriate sampling and analysis strategies. The detailed urinary excretion time courses of specific and non-specific biomarkers of exposure to captan and folpet were established in tree farmers (n = 2) and grape growers (n = 3) over a typical workweek (seven consecutive days), including spraying and harvest activities. The impact of the expression of urinary measurements [excretion rate values adjusted or not for creatinine or cumulative amounts over given time periods (8, 12, and 24 h)] was evaluated. Absorbed doses and main routes-of-entry were then estimated from the 24-h cumulative urinary amounts through the use of a kinetic model. The time courses showed that exposure levels were higher during spraying than harvest activities. Model simulations also suggest a limited absorption in the studied workers and an exposure mostly through the dermal route. It further pointed out the advantage of expressing biomarker values in terms of body weight-adjusted amounts in repeated 24-h urine collections as compared to concentrations or excretion rates in spot samples, without the necessity for creatinine correction

Hazardous substances in frequently used professional cleaning products

A growing number of studies have identified cleaners as a group at risk for adverse health effects of the skin and the respiratory tract. Chemical substances present in cleaning products could be responsible for these effects. Currently, only limited information is available about irritant and health hazardous chemical substances found in cleaning products. We hypothesized that chemical substances present in cleaning products are known health hazardous substances that might be involved in adverse health effects of the skin and the respiratory tract. We performed a systematic review of cleaning products used in the Swiss cleaning sector. We surveyed Swiss professional cleaning companies (n = 1476) to identify the most used products (n = 105) for inclusion. Safety data sheets (SDSs) were reviewed and hazardous substances present in cleaning products were tabulated with current European and global harmonized system hazard labels. Professional cleaning products are mixtures of substances (arithmetic mean 3.5 +/- 2.8), and more than 132 different chemical substances were identified in 105 products. The main groups of chemicals were fragrances, glycol ethers, surfactants, solvents; and to a lesser extent, phosphates, salts, detergents, pH-stabilizers, acids, and bases. Up to 75% of products contained irritant (Xi), 64% harmful (Xn) and 28% corrosive (C) labeled substances. Hazards for eyes (59%) and skin (50%), and hazards by ingestion (60%) were the most reported. Cleaning products potentially give rise to simultaneous exposures to different chemical substances. As professional cleaners represent a large workforce, and cleaning products are widely used, it is a major public health issue to better understand these exposures. The list of substances provided in this study contains important information for future occupational exposure assessment studies