8-OHdG mediates the association of co-exposure to fifty-five typical endocrine-disrupting chemicals with renal function: a cross-section investigation in Southern Chinese adults.

Individual typical endocrine-disrupting chemicals (EDCs), including organophosphate triesters (OPEs), parabens, triclosan (TCS), bisphenols, benzophenones (BPs), phthalates (PAEs), and synthetic phenolic antioxidants (SPAs), are associated with renal dysfunction. However, the combined effects and underlying mechanisms of mixed EDC exposure on renal function remain unclear. Two hundred ninety-nine adult participants were enrolled in the cross-sectional survey conducted in Guangzhou, China. Urinary levels of 7 OPEs, 6 parabens, TCS, 14 bisphenols, 8 BPs, 15 PAEs, 4 SPAs, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined, and estimated glomerular filtration rate (eGFR) was served as the outcome index. We found elevated levels of diphenyl phosphate (DPP), bisphenol A (BPA), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-butyl phthalate (MBP) showed dose-responsive associations with eGFR decline, However, nonlinear associations were observed for bis(2-butoxyethyl) hydrogen phosphate (BBOEP), TCS, 4-hydroxybenzophenone (HBP), mono-n-pentyl phthalate (MnPP), and mono-benzyl phthalate (MBzP). The quantile-based g-computation model demonstrated that a quartile increase in the EDC mixture corresponded to a 0.383-SD decrease (95% CI - 0.658 ~ - 0.108, P = 0.007) in eGFR. Notably, BPA was identified as the primary contributor to this effect. Moreover, 8-OHdG mediated the eGFR decline associated with EDC mixtures with a mediation proportion of 25.49%. A sex-modified effect was also observed (P = 0.004), indicating that exposure to the mixture of EDC was linked to more pronounced renal dysfunction in females. Our novel findings suggest that exposure to a typical mixture of EDCs is associated with renal dysfunction in the general adult population of Southern China. Furthermore, 8-OHdG may play a role in the pathogenesis of EDC mixture-related renal dysfunction.

Empirical analysis of lead neurotoxicity mode of action and its application in health risk assessment.

The mode of action (MOA) framework is proposed to inform a biological link between chemical exposures and adverse health effects. Despite a significant increase in knowledge and awareness, the application of MOA in human health risk assessment (RA) remains limited. This study aims to discuss the adoption of MOA for health RA within a regulatory context, taking our previously proposed but not yet validated MOA for lead neurotoxicity as an example. We first conducted a quantitative weight of evidence (qWOE) assessment, which revealed that the MOA has a moderate confidence. Then, targeted bioassays were performed within an in vitro blood-brain barrier (BBB) model to quantitatively validate the scientific validity of key events (KEs) in terms of essentiality and concordance of empirical support (dose/temporal concordance), which increases confidence in utilizing the MOA for RA. Building upon the quantitative validation data, we further conducted benchmark dose (BMD) analysis to map dose-response relationships for the critical toxicity pathways, and the lower limit of BMD at a 5% response (BMDL5) was identified as the point of departure (POD) value for adverse health effects. Notably, perturbation of the Aryl Hydrocarbon Receptor (AHR) signaling pathway exhibited the lowest POD value, measured at 0.0062 µM. Considering bioavailability, we further calculated a provisional health-based guidance value (HBGV) for children's lead intake, determining it to be 2.56 µg/day. Finally, the health risk associated with the HBGV was assessed using the hazard quotient (HQ) approach, which indicated that the HBGV established in this study is a relative safe reference value for lead intake. In summary, our study described the procedure for utilizing MOA in health RA and set an example for MOA-based human health risk regulation.

Co-exposure of petrochemical workers to noise and mixture of benzene, toluene, ethylbenzene, xylene, and styrene: Impact on mild renal impairment and interaction.

Epidemiological evidence concerning effects of simultaneous exposure to noise and benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) on renal function remains uncertain. In 2020, a cross-sectional study was conducted among 1160 petrochemical workers in southern China to investigate effects of their co-exposure on estimated glomerular filtration rate (eGFR) and mild renal impairment (MRI). Noise levels were assessed using cumulative noise exposure (CNE). Urinary biomarkers for BTEXS were quantified. We found the majority of workers had exposure levels to noise and BTEXS below China's occupational exposure limits. CNE, trans, trans-muconic acid (tt-MA), and the sum of mandelic acid and phenylglyoxylic acid (PGMA) were linearly associated with decreased eGFR and increased MRI risk. We observed U-shaped associations for both N-acetyl-S-phenyl-L-cysteine (SPMA) and o-methylhippuric acid (2-MHA) with MRI. In further assessing the joint effect of BTEXS (ß, -0.164 [95% CI, -0.296 to -0.033]) per quartile increase in all BTEXS metabolites on eGFR using quantile g-computation models, we found SPMA, tt-MA, 2-MHA, and PGMA played pivotal roles. Additionally, the risk of MRI associated with tt-MA was more pronounced in workers with lower CNE levels (P = 0.004). Multiplicative interaction analysis revealed antagonisms of CNE and PGMA on MRI risk (P = 0.034). Thus, our findings reveal negative dose-effect associations between noise and BTEXS mixture exposure and renal function in petrochemical workers. With the exception of toluene, benzene, xylene, ethylbenzene, and styrene are all concerning pollutants for renal dysfunction. Effects of benzene, ethylbenzene, and styrene exposure on renal dysfunction were more pronounced in workers with lower CNE.

Effects of coexposure to noise and mixture of toluene, ethylbenzene, xylene, and styrene (TEXS) on hearing loss in petrochemical workers of southern China.

Many harmful factors existing simultaneously with noise are reported to induce hearing impairment, such as organic solvents. However, the existing hearing safety limits and current risk assessment for hearing loss rely on single noise exposure. It is urgent to clarify the combined effect of noise and other harmful factors on hearing loss. Petrochemical workers are always exposed to noise and organic solvents, mainly benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS), while the combined effect of their coexposure on hearing remains unclear. Herein we conducted a cross-sectional survey, measuring pure-tone audiometry of 1496 petrochemical workers in southern China. Participants exposed to BTEXS were 569, 524, 156, 452, and 177 respectively. Individual cumulative noise exposure (CNE) levels and BTEXS exposure were assessed. The average CNE was 93.27 ± 4.92 dB(A)·years, and the concentrations of BTEXS were far below the occupational exposure limits of China. Logistic regression analyses showed that CNE was consistently positively associated with hearing loss (HL) and high-frequency hearing loss (HFHL) but not related to speech-frequency hearing loss (SFHL). Compared with participants in the lowest quartile of CNE, those in the highest quartile showed an OR of 5.229 (95% CI: 3.179, 8.598) for HFHL. Two-pollutant model analysis indicated that TEXS exposure was positively associated with HL (OR 1.679, 95%CI 1.086, 2.597), SFHL (OR 2.440, 95%CI 1.255, 4.744), and HFHL (OR 1.475, 95%CI 1.077, 2.020). However, no interactions were observed between CNE and TEXS coexposure on hearing loss. In our study, covariates including smoking and drinking status, body mass index (BMI), ear protection and personal protective equipment, and use of earphone/headphone were adjusted. In conclusion, coexposure to noise and low-level TEXS could induce more severe damage on hearing function than exposure to each alone, especially SFHL. Therefore, petrochemical workers simultaneously exposed to noise and TEXS, even at low-level, should be included in hearing protection programs.