Decrease in serum testosterone levels after short-term occupational exposure to diisononyl phthalate in male workers.

OBJECTIVE: The objective of the study was to examine the effects of occupational exposure to diisononyl phthalate (DINP) on serum testosterone levels in male workers. METHODS: From 2015 to 2018, 97 male workers were recruited from six French factories in the plastics industry. In a short longitudinal study, changes over 3 days in the level of total or free serum testosterone and DINP exposure were measured. DINP exposure was measured by urinary biomonitoring: mono-4-methyl-7-oxo-octyl phthalate (OXO-MINP), mono-4-methyl-7-hydroxy-octyl phthalate (OH-MINP) and mono-4-methyl-7-carboxyheptylphthalate (CX-MINP). We further analysed changes in follicle-stimulating hormone, luteinising hormone, total testosterone to oestradiol ratio and two bone turnover markers (procollagen-type-I-N propeptide, C terminal cross-linking telopeptide of type I collagen), and erectile dysfunction via standardised questionnaires (International Index of Erectile Function, Androgen Deficiency in Aging Males). Linear mixed models were used with the variables 'age' and 'abdominal diameter' included as confounder. RESULTS: Increased urinary OXO-MINP was associated with a significant decrease in total serum testosterone concentrations, but only for workers who exhibited the smallest variations and lowest exposures (p=0.002). The same pattern was observed for CX-MINP but was not significant; no association with OH-MINP was detectable. More self-reported erectile problems were found in workers exposed directly to DINP at the workstation (p=0.01). No changes were observed for the other biological parameters. CONCLUSIONS: Short-term exposure to DINP is associated with a decrease in total serum testosterone levels in male workers. Our results suggest that DINP could present weak antiandrogenic properties in humans, but these need to be confirmed by other studies.

Early Effect Markers and Exposure Determinants of Metalworking Fluids Among Metal Industry Workers: Protocol for a Field Study.

BACKGROUND: Exposure to aerosols from metalworking fluids (MWF) has previously been related to a series of adverse health outcomes (eg, cancer, respiratory diseases). Our present epidemiological study focuses on occupational exposures to MWF and a panel of exposure and effect biomarkers. We hypothesize that these health outcomes are caused by particle exposure that generates oxidative stress, leading to airway inflammation and ultimately to chronic respiratory diseases. We aimed to assess whether MWF exposure, in particular as characterized by its oxidative potential, is associated with biomarkers of oxidative stress and inflammation as well as genotoxic effects. OBJECTIVE: The ultimate goal is to develop exposure reduction strategies based on exposure determinants that best predict MWF-related health outcomes. The following relationships will be explored: (1) exposure determinants and measured exposure; (2) occupational exposure and preclinical and clinical effect markers; (3) exposure biomarkers and biomarkers of effect in both exhaled breath condensate and urine; and (4) biomarkers of effect, genotoxic effects and respiratory symptoms. METHODS: At least 90 workers from France and Switzerland (30 controls, 30 exposed to straight MWF and 30 to aqueous MWF) were followed over three consecutive days after a nonexposed period of at least two days. The exposure assessment is based on MWF, metal, aldehyde, and ultrafine particle number concentrations, as well as the intrinsic oxidative potential of aerosols. Furthermore, exposure biomarkers such as metals, metabolites of polycyclic aromatic hydrocarbons and nitrosamine are measured in exhaled breath condensate and urine. Oxidative stress biomarkers (malondialdehyde, 8-isoprostane, 8-hydroxy-2'-deoxyguanosine, nitrates, and nitrites) and exhaled nitric oxide, an airway inflammation marker, are repeatedly measured in exhaled breath condensate and urine. Genotoxic effects are assessed using the buccal micronucleus cytome assay. The statistical analyses will include modelling exposure as a function of exposure determinants, modelling the evolution of the biomarkers of exposure and effect as a function of the measured exposure, and modelling respiratory symptoms and genotoxic effects as a function of the assessed long-term exposure. RESULTS: Data collection, which occurred from January 2018 until June 2019, included 20 companies. At the date of writing, the study included 100 subjects and 29 nonoccupationally exposed controls. CONCLUSIONS: This study is unique as it comprises human biological samples, questionnaires, and MWF exposure measurement. The biomarkers collected in our study are all noninvasive and are useful in monitoring MWF exposed workers. The aim is to develop preventative strategies based on exposure determinants related to health outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13744.

Simultaneous determination of aromatic and chlorinated compounds in urine of exposed workers by dynamic headspace and gas chromatography coupled to mass spectrometry (dHS-GC-MS).

Mixed exposure to chemical products is a topical issue for occupational health and often includes exposure to volatile organic compounds (VOCs). As very few methods are available for evaluating these mixed exposures, the aim of this work was to develop a simple biomonitoring method to assess simultaneous occupational exposures to chlorinated and aromatic VOCs by analyzing the unmetabolized fraction of the VOCs in the urine of workers. Volatile organic compounds were analyzed using dynamic headspace gas chromatography coupled to mass spectrometry (dHS-GC-MS), and 11 unmetabolized urinary VOCs were measured into headspace phase, without any time-consuming pretreatment. Simultaneously, a standardized collection protocol was designed to avoid VOC losses or the contamination of urinary samples. The calibration samples were real urines, spiked with known amounts of the VOC mixtures studied. Test investigations were performed on potentially exposed workers in three factories in order to assess the effectiveness of both the collection protocol and analytical method. A satisfactory level of sensitivity was achieved, with limits of quantification (LOQ) between 10 and 15 ng/L obtained for all VOCs (except for styrene at 50 ng/L). Calibration curves were linear in the 0-20 µg/L range tested, with R2 correlation coefficients of 0.991 to 0.998. At the lowest concentration tested (0.08 µg/L), within-day precision varied from 2.1 to 5.5% and between-day precision ranged from 2.7 to 8.5%. Sample stability at -20 °C required that urinary samples be analyzed within 3 months. Even though the urinary concentrations of VOCs used in the plants were mostly quite low, significant differences between post-shift and pre-shift were observed. In conclusion, a fast, sensitive, specific and easy-to-use method has been developed for extracting VOCs from human urine using dHS-GC-MS. The method described has proven to be reliable for assessing current occupational exposure to chlorinated and aromatic VOCs in France.

Maintenance of Low-Pressure Carburising Furnaces: A Source of PAH Exposure.

OBJECTIVES: Low-pressure carburising is a new technology used to harden steel; the process has been shown to be a source of considerable polycyclic aromatic hydrocarbons (PAH) pollution. Some PAH are carcinogenic, and activities such as furnace maintenance may thus represent a risk to workers. Occupational exposure during these operations should therefore be assessed. METHODS: In this study, the PAH-related carcinogenic risk associated with furnace maintenance was assessed by monitoring atmospheric levels of benzo[a]pyrene (BaP), a representative marker, alongside urinary levels of 3-hydroxybenzo[a]pyrene (3-OHBaP), one of its metabolites. PAH exposure levels were monitored during seven sampling campaigns in four different factories specialized in heat-treatment of mechanical workpieces for the automotive and helicopter industries. Two types of furnace were studied, and 37 individuals were monitored. RESULTS: Values up to 20-fold the French regulatory value of 150 ng/m3 for atmospheric BaP, and, for urinary 3-OHBaP values up to 40-fold the French biological limit value (BLV) of 0.35 nmol/mol of creatinine were detected. Very high concentrations of BaP, close to or even exceeding those found in coal-tar pitch (up to about 20 g/kg), were measured in residues (tars, dusts) deposited inside the furnace. Even when adequate and suitable personal protective equipment was used, urinary 3-OHBaP values often exceeded the BLV. We hypothesize that this exposure is linked to insidious and fortuitous dermal contamination through contact with factory equipment and staining.

1-Hydroxypyrene and 3-hydroxybenzo[a]pyrene as biomarkers of exposure to PAH in various environmental exposure situations.

OBJECTIVE: To evaluate the utility of urinary 3-hydroxybenzo[a]pyrene (3-OH-B[a]P) as a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs) in various environmental exposure scenarios alongside the more usually studied 1-hydroxypyrene (1-OH-Pyr). METHODS: Two groups of 15 and 10 non smoking, healthy men and women, were exposed for approximately 6h to ambient air at two outdoor locations close to metallurgical industries, and at one indoor location in an urban setting. Atmospheric measurements of 16 "priority" PAHs were carried out during each exposure. Urinary 1-OH-Pyr and 3-OH-B[a]P were also analysed, samples being taken the morning before exposure, at the end of exposure, then 4 and 15 h after the end of exposure. Urinary 1-OH-Pyr and 3-OH-B[a]P were analysed using high performance liquid chromatograph with fluorescence detection. Limits of detection (LOD) were 0.092 nmol/L and 0.28 pmol/L for 1-OH-Pyr and 3-OH-B[a]P respectively. RESULTS: Average ambient air concentrations varied from 0.27 to 2.87 ng/m(3) for pyrene, 0.04 to 1.20 ng/m(3) for B[a]P, and from 70.0 to 910.6 ng/m(3) for the sum of the 16 PAH (SigmaPAHs). Concentrations of 1-OH-Pyr were not correlated with atmospheric concentrations of PAHs to which subjects were exposed, nor with the concentrations of 3-OH-B[a]P. Nearly 80% of measurements of 3-OH-B[a]P were lower than the LOD and no relationship between atmospheric concentrations and urinary metabolites was observable. However, the percentage of post-exposure values of 3-OH-B[a]P greater than the LOD increased significantly with the median of atmospheric concentrations of Pyr, B[a]P and SigmaPAH at the different sites (test of linear trend, p<0.02 in all cases). CONCLUSION: Although we used very sensitive techniques for the measurements of urinary metabolites, especially for 3-OH-B[a]P, neither 1-OH-Pyr nor 3-OH-B[a]P were an unequivocal biomarker of exposure to atmospheric PAHs in environmental exposure scenarios relevant to the general population. It would be interesting to investigate other urinary monohydroxy PAH metabolites in this context.