Toxicology and Industrial Health

Lee, JaeHee; Cho, AhRang; Gautam, Ravi; Kim, YeonGyeong; Shin, SoJung; Song, EunSeob; Kim, HyeonJi; Yang, SuJeong; Acharya, Manju; Jo, JiHoon; Maharjan, Anju; Shim, IlSeob; Kim, Hyun-Mi; Kim, PilJe; Kim, TaeSung; Lee, JongKwon; Kang, MiJeong; Jeong, TaeCheon; Kim, ChangYul; Kim, HyoungAh; Heo, Yong

doi: 10.1177/0748233719869514pmid: 31462197

In commercial products such as household deodorants or biocides, didecyldimethylammonium chloride (DDAC) often serves as an antimicrobial agent, citral serves as a fragrance agent, and the excipient ethylene glycol (EG) is used to dissolve the active ingredients. The skin sensitization (SS) potentials of each of these substances are still being debated. Moreover, mixtures of DDAC or citral with EG have not been evaluated for SS potency. The in vitro alternative assay called human Cell Line Activation Test (h-CLAT) and Direct Peptide Reactivity Assay (DPRA) served to address these issues. On three independent runs of h-CLAT, DDAC and citral were predicted to be sensitizers while EG was predicted to be a non-sensitizer and also by the DPRA. Mixtures of DDAC or citral with EG at ratios of 7:3 and 1:4 w/v were all positive by the h-CLAT in terms of SS potential but SS potency was mitigated as the proportion of EG increased. Citral and its EG mixtures were all positive but DDAC and its EG mixtures were all negative by the DPRA, indicating that the DPRA method is not suitable for chemicals with pro-hapten characteristics. Since humans can be occupationally or environmentally exposed to mixtures of excipients with active ingredients, the present study may give insights into further investigations of the SS potentials of various chemical mixtures.

Boran, Halis; Terzi, Serap

doi: 10.1177/0748233719869531pmid: 31462198

Contamination of the aquatic environment by plastic industrial products and their by-products is remarkable. Because of their physical, chemical, and biological degradation resistance, plasticizers can enter the food chain of living organisms, accumulate in the body and generate toxic effects. Here we determined the potential toxic effects of bis(2-ethylhexyl) phthalate (DEHP) plasticizer to larval (72 h post fertilization) zebrafish (Danio rerio) by analyzing changes in expression levels of stress-related genes (p53, rad51, and xrcc5) by the quantitative real-time polymerase chain reaction. Also, possible DNA damage by DEHP in larvae was determined. The concentration of DEHP (0–160 mg/l) that killed 50% of the larval zebrafish within 96 h was 54.02 mg/l. There was a concentration-related increase in DNA damage in cells from larvae exposed (96 h) to DEHP. DNA damage of 31.13% (mean ± standard error of the mean) was observed in larvae at the highest sublethal DEHP concentration (10 mg/l). Some significant differences in the induction of stress-related genes were also observed in larvae exposed to DEHP relative to control (p < 0.05). The conclusion drawn from this ecotoxicological risk assessment is that, under present use and exposure patterns, DEHP presents a small hazard to zebrafish larvae.

Hosohata, Keiko; Mise, Nathan; Kayama, Fujio; Iwanaga, Kazunori

doi: 10.1177/0748233719869548pmid: 31462196

The aim of this study was to examine whether a peroxisome proliferator-activated receptor (PPAR)-γ agonist could affect cadmium (Cd)-induced cytotoxicity via the increased expression of megalin, one of the uptake pathways, using renal epithelial LLC-PK1 cells. The treatment with 1 µM Cd for 24 h was not cytotoxic; however, when the cells were pretreated with 0.1 µM pioglitazone for 12 h and then exposed to 1 µM Cd for 24 h, significant accumulation of Cd and cytotoxicity were detected, with an increase in megalin mRNA expression. In addition, pretreatment with pioglitazone significantly increased the Cd-induced generation of hydrogen peroxide and cell apoptosis. The augmented Cd-induced cytotoxicity and apoptosis on preincubation with pioglitazone were inhibited by prior treatment with GW 9662 (PPAR-γ antagonist). These findings suggest that a PPAR-γ agonist could augment Cd-induced oxidative injury and cell apoptosis, possibly dependent on the expression level of the uptake pathway.

Owumi, Solomon E; Dim, Uche J; Najophe, Eseroghene S

doi: 10.1177/0748233719863287pmid: 31337283

The adverse health consequences of environmental, occupational, and dietary exposure to either diethylnitrosamine (DEN) or cadmium (Cd) have been widely investigated. However, because most environmental exposures to xenobiotics do not occur in isolation but in mixtures, the effects of simultaneous exposure to both DEN and Cd on hepatorenal function deserves investigation. The present study investigated the impact of 7 days oral co-exposure to 10 mg/kg body weight (b.w.) of DEN and 5 mg/kg b.w. of Cd on biomarkers of hepatic and renal functions, antioxidant defense systems, and oxidative stress indices in the liver and kidney of prepubertal rats. The results showed that the significant (p < 0.05) increases in the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, urea, and creatinine following separate administration of DEN and Cd to rats were further increased in the co-exposure group. Moreover, marked decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase as well as glutathione levels following individual administration of DEN and Cd to rats were exacerbated in the co-exposure group. Further, the marked increase in the lipid peroxidation level and the histopathological lesions in the liver and kidney of rats treated with DEN or Cd alone were intensified in the co-exposure group These findings indicate that co-exposure to DEN and Cd elicited more severe hepatic and renal oxidative damage in the rats, thus suggesting a greater risk to humans who are co-exposed to them.

Fatima, Ravish; Ahmad, Riaz

doi: 10.1177/0748233719863632pmid: 31370753

Metal oxide nanoparticles (NPs) have widespread uses ranging from nanoelectronics to nanotherapeutics. Because of their expanding industrial applications, a better understanding of their toxicity is needed. So far, limited reports are available on chromium oxide NPs (Cr2O3 NPs) toxicity. In this work, Cr2O3 NPs were synthesized and characterized in a sequential manner using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy. Dose- and time-dependent toxicity assessment of Cr2O3 NPs was carried out in Wistar rats by examining liver function biomarkers, tissue histopathology, micronuclei (MN) formation, and chromosomal aberrations (CAs) in bone marrow along with sperm abnormalities. The results of this study demonstrated typical XRD and FTIR patterns of Cr2O3 NPs with a size of approximately 23.47 nm. Animals exposed to Cr2O3 NPs, exhibited a significant increase in aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma glutamyltransferase, and total bilirubin, signifying liver injury. Histopathology data also supported the marked alterations in the liver biochemistry of NPs-exposed animals. Further, an increase in the frequency of MN, CA, and sperm abnormalities suggested Cr2O3 NPs-mediated genotoxicity. It is, therefore, suggested that possible safety issues of Cr2O3 NPs should be addressed promptly with limited future use in occupational settings.

Benkhalifa, Abdelaziz; Ayadi, Mohamed

doi: 10.1177/0748233719869509pmid: 31462195

The absence of studies that investigate the causes and risk factors of nonfatal occupational injury in Tunisia inhibits the development of effective preventive strategies. The objective of this study was to identify the causes and risk factors of nonfatal occupational injury in the private sector in Tunisia. We used retrospective data derived from the occupational injury reporting forms submitted to the Caisse Nationale d’Assurance Maladie. A sample of 42,293 workers in the private sector for 2014 contains information on sociodemographic variables. Multivariable Poisson regression was used to investigate the association of cause-specific injury with demographic variables. The leading causes of nonfatal occupational injury were “falls” (employee fall and falling objects; 36%) and “struck by objects” (23%). Male employees were at higher risk of “exposure to extreme temperatures” (PR = 12 [7–45]), “asphyxia and poisoning” (PR = 4 [2.4–12]), “transport and handling” (PR = 2.4 [1.9–5]), “falling objects” (PR = 2.3 [1.4–3.7]), and “employee fall” (PR = 1.2 [1.1–1.5]). Although, rural areas were at higher risk to “asphyxia and poisoning” (PR = 3.6 [1.1–11.4]), “transport and handling” (PR = 2.5 [1.3–5.4]), and “burns” (PR = 1.3 [1.1–3]). It is important that effective interventions be developed to minimize the impact of falls and “struck by objects.” The most vulnerable categories to occupational injury are less educated men, rural residents aged between 15 years and 24 years, and elderly employees (55 years and over). Thus, our findings can contribute to the planning of prevention intervention programs that should expand to the most vulnerable categories.