Among the possible risk factors for male reproduction, exposure to phthalates and alkylphenols is widely documented. This study evaluated the possible association between chemical exposure and the quality of the seminal fluid of 105 subjects in a fertility clinic. The urinary levels of seven phthalate metabolites (monoethylphthalate, MEP; monobenzylphthalate, MBzP; mono n-butylphthalate, MnBP; mono-(2-ethylhexyl) phthalate, MEHP; mono(2-ethyl-5-hydroxyhexyl) phthalate, MEHHP; mono-n-octylphthalate, MnOP; mono-isononylphthalate, MiNP) and bisphenol A (BPA), were analysed by high performance liquid chromatography/tandem mass spectrometry HPLC/MS/MS. The regression analysis showed that the semen volume was positively associated with MnBP, MnOP and BPA levels while was negatively associated with MiNP levels. The sperm concentration had a significant inverse relationship with MEP levels. A negative association was found between the use of plastic containers for food storage (p = 0.037) and semen volume (3.06 vs. 2.30 mL as average values, never vs daily). A significant positive correlation emerged (p < 0.005) between the consumption of canned food and the levels of BPA (2.81 vs. 0.14 µg/g creat as average values, daily vs. never) and between the use of perfumes and levels of MEP (389.86 vs. 48.68 µg/g creat, as average values, daily vs. never). No further statistically significant associations were found, even considering the working activity. Some evidence emerged about the possible link between exposure and seminal fluid quality: further case/control or prospective studies will allow us to confirm this causality hypothesis.

Background: Urinary cotinine, a metabolite of nicotine, is a marker of tobacco smoke exposure. A cutoff value for cotinine concentration can be set to distinguish smokers from non-smokers, independently from self-declared status. Method: Cotinine was determined by isotopic dilution High Performance Liquid Chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) between 2013 and 2014 on urine samples of a population of 1075 subjects. Results: 296 subjects have a cotinine level higher than 100 μg/g of creatinine (cutoff), with a median cotinine concentration of 1504.70 μg/g of creatinine. The mean is 27.5% of smokers and 60.5% in this group are females. The median value for non-smokers is 5.6 μg/g of creatinine. Two hundred and seventy-five subjects declared to be smokers in the questionnaire, but 6 (2.2%) present urinary cotinine levels lower than cutoff; 800 subjects declared to be non-smokers, but 26 of them presented urinary cotinine levels that were higher than the cutoff (3.3%). Conclusion: Using the cutoff of 100 μg/g, the misclassification of smokers resulted to be 2.2%, indicating that the selected value is suitable for studying the human exposures to environmental and occupational pollutants, including those produced by smoking.

The xenoestrogenicity of some plasticisers (phthalates and bisphenol A) is documented in the literature and may pose a risk to female reproductive health. The aim of this study was to assess exposure to six phthalates. This was achieved by measuring their respective metabolites (mono-ethylphthalate (MEP); mono-n-butylphthalate (MnBP); mono-n-ottylphthalate (MnOP); and monobenzylphthalate (MBzP)), as well as the sum of two of the diethyl-hexyl phthalate metabolites-(∑DEHP) and bisphenol A (BPA) in a female population with infertility problems, and by conducting a correlation analysis between infertility factors, work activities, and lifestyle habits, in order to formulate a causal hypothesis. A cross-sectional epidemiological study was carried out and women under 43 years of age were recruited from an assisted reproduction technology (ART) center; the sample of 186 women was given a specific questionnaire and a spot urine sample was collected. Phthalate metabolites and urinary BPA were analyzed by HPLC/MS/MS. The results showed significantly higher mean values for MEP in women with recurrent pregnancy loss (RPL) (820.5 ± 1929.5 µg/g of creatinine) and idiopathic infertility (230.0 ± 794.2 µg/g of creatinine) than in women with other infertility factors (76.9 ± 171.8 µg/g of creatinine). Similarly, for MnOP levels, women with idiopathic infertility (2.95 ± 3.44 µg/g of creatinine) showed significantly higher values than women with the other infertility factors taken together (1.35 ± 2.05 µg/g of creatinine). Women with tubal factors of infertility, RPL, and endocrine dysfunctions show higher values of DEHP (p = 0.032). Considering occupations, women working in commerce showed more than twice as much urinary BPA levels (1.10 ± 0.48 µg/g of creatinine) compared to women working in other industries (0.45 ± 0.35 µg/g of creatinine). The presence of significantly higher values of certain phthalates, DEHP in particular, especially in women with RPL and idiopathic infertility, suggests a possible involvement of these compounds as competing factors in reproductive issues. The study of sources of exposure suggested that the working activity in trade, as a casher in particular, represents a major one for BPA (p = 0.015).

Phthalates are widely used in the industrial manufacture of many products. Some phthalates have shown reproductive toxicity in humans, acting as endocrine disruptors, so they were included in the authorization process defined in Reg. CE 1907/2006 (REACH). Two groups of population were recruited, before and after the inclusion of some phthalates in the authorization list in REACH: the first group of 157 volunteers was studied in 2011 and the second, 171 volunteers, in 2016. Each subject completed a questionnaire about personal lifestyle, working activities and use of chemical products. The main urinary metabolites of five phthalates were analyzed by HPLC/MS/MS: mono(2-ethylhexyl)phthalate (MEHP) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) for di(2-ethylhexyl)phthalate (DEHP) exposure; monoethylphthalate (MEP) for diethylphtahate (DEP); monobenzylphthalate (MBzP) for butylbenzylphtahalate (BBP) and dibenzylphthalate (DBzP), mono-n-butylphthalate (MnBP) for butylbenzylphtahalate (BBP) and di-n-butylphthalate (DnBP). The results show a significant difference for all metabolites between the two periods, with the exception of MEP in women. The comparison of the two sets of results shows a decrease in urinary metabolites excretion from 2011 to 2016, statistically significant for the three phthalates included in Annex XIV of REACH. DEP, not currently included in the list for authorization, maintains a constant presence in the daily life of the population, particularly for women.

Urinary concentrations of 16 different exposure biomarkers to metals were determined at the beginning and at the end of a working shift on a group of workers in the metal carpentry industry. Five different oxidative stress biomarkers were also measured, such as the oxidation products of RNA and DNA metabolized and excreted in the urine. The results of workers exposed to metals were compared to those of a control group. The metal concentrations found in these workers were well below the occupational exposure limit values and exceeded the mean concentrations of the same metals in the urine of the control group by a factor of four at maximum. Barium (Ba), mercury (Hg), lead (Pb) and strontium (Sr) were correlated with the RNA oxidative stress biomarker, 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), which was found able to discriminate exposed workers from controls with a high level of specificity and sensitivity. The power of this early diagnostic technique was assessed by means of the ROC curve. Ba, rubidium (Rb), Sr, tellurium (Te), and vanadium (V) were correlated with the level of the protein oxidation biomarker 3-Nitrotyrosine (3-NO₂Tyr), and Ba, beryllium (Be), copper (Cu), and Rb with 5-methylcytidine (5-MeCyt), an epigenetic marker of RNA damage. These effect biomarkers can help in identifying those workers that can be defined as “occupationally exposed” even at low exposure levels, and they can provide information about the impact that such doses have on their health.

This study aimed to identify sensitive and noninvasive biomarkers of early cyto-genotoxic, oxidative and inflammatory effects for exposure to volatile organic compounds (VOCs) in shipyard painters. On 17 (11 spray and 6 roller) painters (previously characterized for VOCs exposure to toluene, xylenes, ethylbenzene, ethyl acetate) and on 18 controls, we performed buccal micronucleus cytome (BMCyt) assay; Fpg-comet assay on lymphocytes; detection of urinary 8-oxoGua (8-oxo-7,8-dihydroguanine), 8-oxodGuo (8-oxo-7,8-dihydro-2′-deoxyguanosine) and 8-oxoGuo (8-oxo-7,8-dihydroguanosine), and cytokines release on serum. We found induction of cyto-genotoxicity by BMCyt assay and inflammatory effects (IL-6 and TNFα) in roller painters exposed to lower VOC concentrations than spray painters. In contrast, in both worker groups, we found direct and oxidative DNA damage by comet assay (with slightly higher oxidative DNA damage in roller) and significant increase of 8-oxoGuo and decrease of 8-oxodGuo and 8-oxoGua in respect to controls. The cyto-genotoxicity observed only on buccal cells of roller painters could be related to the task’s specificity and the different used protective equipment. Although limited by the small number of subjects, the study shows the usefulness of all the used biomarkers in the risk assessment of painters workers exposed to complex mixtures.