Toxicology and Industrial Health

Esmaeili, Sayed Vahid; Alboghobeish, Ali; Feyzi, Vafa; Ravannakhjavani, Fatemeh; Zendehdel, Rezvan

doi: 10.1177/07482337241286187pmid: 39313242

The utilization of synthetic dyes increases the risk to human health. Despite the progress of information on azo dyes, very little attention has been reported on toxicity assessment of anthraquinone dyes. Solvent Blue 35 (SB35) is one of the anthraquinone dyes likely to be encountered because of its increasing use in various industries. Whereas the design of laboratory tests is very expensive, in silico screening was used to predict the metabolic profile and toxicity effect of SB35. MetaTox software was used to predict the metabolites of phase I and II in two layers. Since airborne exposure has been considered, the pathways of inhalation and dermal absorption of SB35 were investigated through the SwissADME model based on the modified Lipinski’s rule of five. To predict the biological effect and toxicity of SB35 and each of the metabolites, PASS online software was used. Chemical activity was considered according to the probability of activation values (Pa) higher than the probability of inactivation values (Pi). N- dealkylation of SB35 was predicted in the first layer, while seven active compounds were obtained in the second layer from phases I and II reactions. Investigating the physicochemical properties of SB35 confirmed inhalation absorption for occupational exposure scenarios. All metabolites are absorbed from intestinal routes based on the RO5 rules. SB35 and their metabolites have an effective substrate role for the sub-type of CYP 450 enzymes. The toxicity effect of carcinogenicity for SB35 and mutagenicity for metabolites are predicted while confirmed with some biological effects. However, reproductive disorders are pointed with SB35 by probability higher than 70%. Virtual screening methods are efficient tools for creating cost-effective predictions in the hazard’s evaluation of SB35. However, a perspective view is suggested before decision-making for laboratory designing tests.

Higley, Cole M; Waligora, Katelyn D; Clore, Jessica R; Timmons, Shannon C; Kuzmanov, Aleksandra

doi: 10.1177/07482337241287967pmid: 39344986

Research has shown that exposure to bisphenol A (BPA), a widely used plasticizer, can lead to meiotic errors, resulting in poor reproductive cell quality and infertility. Health-related concerns have prompted the search for BPA alternatives; however, evidence suggests that currently used BPA analogs, such as bisphenol S (BPS), may pose similar risks to human health. While the effects of BPA on female fertility are well documented, the impact of BPA exposure on sperm quality is poorly understood. To better understand the effects of bisphenol analogs on spermatogenesis, we synthesized a less investigated BPA analog, tetramethyl bisphenol F (TMBPF), and compared its reprotoxic potential to that of widely used BPA and BPS using C. elegans-based assays. We evaluated germ cell count, spermatid size, morphology, and activation in males treated with 0.5 mM ethanol-dissolved bisphenol analogs for 48 h as well as their cross-progeny number and viability. Our results indicated that all of the evaluated bisphenol analogs—BPA, BPS, and TMBPF—adversely affect male fertility to varying degrees. Whereas all three bisphenols reduced spermatid size, only BPA exposure resulted in impaired spermatid activation and significantly reduced brood size. In addition, a decrease in embryonic viability, suggestive of an increased incidence of sperm chromosomal aberrations, was observed following exposure to all of the tested bisphenols. Further investigation is necessary to fully elucidate the underlying mechanisms and implications of BPA, BPS, and TMBPF on spermatogenesis.

Massarsky, Andrey; Fung, Ernest S; Evans, Veneese JB; Maier, Andrew

doi: 10.1177/07482337241289184pmid: 39370434

Occupational exposure limits (OELs) and occupational exposure bands (OEBs) provide quantitative benchmarks for worker health protection. If empirical toxicology data are insufficient to derive an OEL, an OEB is often assigned using partial toxicology data along with other relevant hazard information. There is no consensus methodology to assign OEBs for chemicals lacking any empirical toxicology data. Thus, this study developed an in silico framework for OEB assignment of data poor compounds. It relies upon computational tools to evaluate standard toxicological end points and to assign reliability ratings, which are then used to assign Global Harmonization System (GHS) hazard categories. Subsequently, the hazard categories are entered into the National Institute for Occupational Safety and Health (NIOSH) occupational exposure banding tool to assign bands for individual end points as well as an overall OEB. As a proof-of-concept, five compounds with established OELs (i.e., “knowns”) were evaluated. The knowns were assigned to overall OEBs C, D, or E, four of which were equal to or lower than the OEBs based on actual harmonized GHS categories as well as established OELs, indicating that the OEBs assigned using this framework are likely to be protective. Subsequently, five compounds with little to no experimental data and no established OELs from any U.S. agency or consensus OEL-setting organizations were evaluated (i.e., “unknowns”). The unknowns were assigned to overall OEBs D or E. It was concluded that the proposed framework can be used to assign protective OEBs to compounds with little to no toxicology testing data. As additional data become available, the compound may be de-risked, and a precautionary OEB (or an OEL) can be assigned. The proposed framework provides an example of a practical methodology to evaluate data poor compounds and shows that the output of this framework is expected to be protective of worker health.

Yang, Jing; Lu, Jiaojiao; Cao, Luoyuan; Dong, Wenxu; Zheng, Xian; Fu, Xianguo

doi: 10.1177/07482337241295474pmid: 39437026

Citreoviridin (CIT) is a mycotoxin produced by various fungi. Although CIT has been reported to cause neurotoxicity, the molecular mechanism is poorly understood. Therefore, the aim of this study was to investigate the effects and molecular mechanisms of CIT in neurotoxicity. Different concentrations of CIT were treated to rat pheochromocytoma (PC-12 cells), and oxidative stress parameters, cytokine levels, and cell apoptosis were evaluated. CIT treatment (5 and 10 μM) significantly induced PC-12 cell apoptosis and increased lactate dehydrogenase activity. Additionally, CIT treatment induced oxidative stress, as evidenced by a significant increase in intracellular levels of reactive oxygen species, malondialdehyde, and superoxide dismutase and a decrease in glutathione activity. Moreover, CIT treatment induced an inflammatory response, as evidenced by a significant increase in the intracellular levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1-beta in PC-12 cells. Furthermore, quantitative PCR and western blotting showed that CIT treatment increased both the protein and mRNA expression of GADD45α and p21 in PC-12 cells, suggesting that CIT may induce apoptosis by inhibiting cell cycle, blocking cell growth, and damaging DNA. Conclusively, this study contributes the understanding the toxicity mechanisms of CIT to nerve cells.

Stevens, Michael E; Tuttle, Brett P; Brew, David W; Paustenbach, Dennis J

doi: 10.1177/07482337241293201pmid: 39447016

Mesothelioma is a fatal disease that has historically been associated with exposure to airborne asbestos. Because occupational asbestos exposures dropped dramatically in the late 1960s and early 1970s, far fewer cases of mesothelioma today are due to these fibers but, instead, are usually a result of the aging process or genetic predisposition. In May of 2022, a Morbidity and Mortality Weekly Report (MMWR) was issued by the Centers for Disease Control and Prevention (CDC) regarding malignant mesothelioma incidence in women from 1999 to 2020. While this MMWR alerted citizens to the continued presence of the disease, after reading this article one might have thought that the CDC was suggesting that the disease was increasing in women due to asbestos exposures (which it is not). In the present analysis, we investigate several factors related to the interpretation of epidemiological data for mesothelioma, including the role of asbestos as a risk factor over time. The authors conducted a review of the scientific community’s understanding of mesothelioma incidence and asbestos exposures amongst women, as well as an investigation of the methods and references in the MMWR article. Although various articles have recently discussed the incidence of both peritoneal and pleural mesothelioma in women, it is fortunate that the age-adjusted rates for mesothelioma have remained flat (neither increased nor decreased significantly) in women for the past 50 years. Incredibly few women in the U. S. have had appreciable cumulative exposures to any type of asbestos (chrysotile, amosite, or crocidolite) in the workplace or from the ambient environment, especially since about 1965–1970. In this paper, we highlight six factors that should be considered when evaluating the incidence of mesothelioma amongst American women in the current era. Without sufficient consideration of these factors, improper conclusions have been drawn over the past several years.