Toxicology and Industrial Health

(Z)-1-Chloro-2,3,3,3-tetrafluoropropene (HCFO-1224yd(Z)) is a colorless gas used as a single substance or in a mixture with other substances for refrigeration. The 4-h rat inhalation LC₅₀ values from two studies were reported to be >20,180 ppm and >213,100 ppm. HCFO-1224yd(Z) is not expected to undergo significant metabolism. The no-observed-effect level of HCFO-1224yd(Z) for cardiac sensitization (in dogs) was 75,000 ppm. In a 5-day repeat inhalation study in rats, the only observation noted was repetitive movement of the mouth/jaws in some animals in the 50,000-ppm exposure group for 1–2 days during the first 3 exposure days. The toxicological significance of this observation was unknown; therefore, the study no-observed-adverse-effect level (NOAEL) was established at 50,000 ppm. In a good laboratory practice (GLP)-compliant, 4-week inhalation study in rats, there were no test substance-related adverse effects noted at any exposure concentration. The study NOAEL was established at 40,000 ppm. In a GLP-compliant inhalation developmental toxicity study, female rats were exposed for 6 h/day from gestation day 6 through 19. There were no test substance-related adverse effects on either the maternal or fetal rats at any exposure concentration. The NOAEL for developmental effects was established at 20,000 ppm. There are no chronic toxicity or carcinogenicity studies available. HCFO-1224yd(Z) gave mixed results in in vitro genotoxicity assays but was negative in an in vivo micronucleus assay. The NOAEL of 40,000 ppm for HCFO-1224yd(Z) from the 4-week, GLP-compliant inhalation study in rats was used at the point of departure (POD) for workplace environmental exposure level (WEEL) value development. This POD was adjusted to account for interindividual variability, duration of exposure, and database limitations. The resulting 8-h time-weighted average WEEL value of 1000 ppm is expected to provide a significant margin of safety against any potential adverse health effects in workers exposed to HCFO-1224yd(Z).

Trifluoroiodomethane (CF₃I) is a colorless and odorless gas used primarily as a fire suppressant. CF₃I has low acute inhalation toxicity. The no-observed adverse effect level (NOAEL) of CF₃I for cardiac sensitization in dogs was 2000 ppm. The potential effects of 4-week inhalation exposure in both rats and mice have been examined. In rats, the NOAEL was 10,000 ppm, and in mice, the NOAEL was 10,000 ppm. In a subchronic inhalation study in rats, the lowest observed adverse effect level (LOAEL) was 20,000 ppm for thyroid-related effects; the study NOAEL (for non-thyroid-related effects) was 20,000 ppm. In a reproductive/developmental inhalation toxicity study in rats, 20,000 ppm CF₃I produced minimal general toxicity and no indication of reproductive or developmental toxicity. The LOAEL for parental toxicity (based on thyroid hormone effects) was 2000 ppm; excluding thyroid effects, the parental NOAEL was 7000 ppm CF₃I. The observed effects on the thyroid in rats were considered of less relevance to human risk assessment than the other observed systemic effects because of known species-specific differences in sensitivity to thyroid hormone perturbations. There are no chronic toxicity or carcinogenicity studies available. CF₃I had mixed results in various in vitro and in vivo genotoxicity assays. The NOAEL of 7000 ppm from the reproductive/developmental inhalation study was used as the point of departure (POD) for workplace environmental exposure level (WEEL) value development. This POD was adjusted to account for interindividual variability, duration of exposure, and database limitations. The resulting 8-h time-weighted average WEEL value of 500 ppm is expected to provide a significant margin of safety against any potential adverse health effects in workers exposed to CF₃I. A 15-min short-term exposure limit of 1500 ppm was also established to protect workers from potential cardiac effects produced by acute, high-dose inhalation of CF₃I.

Many bisphenol A (BPA) analogs have been commercially used recently, such as 2,2-bis(4-hydroxyphenyl)butane (BPB), 4,4′-ethylidenebisphenol, 4,4′-methylenediphenol (BPF), 4,4′-(1,4-phenylenediisopropylidene)bisphenol (BPP), 4,4′-dihydroxydiphenyl sulfone (BPS), 4,4′-cyclohexylidenebisphenol (BPZ), 4,4′-(hexafluoroisopropylidene)diphenol (BPAF), 4,4′-(1-phenylethylidene)bisphenol (BPAP), and 2,2-bis(4-hydroxy-3,5-dimethylphenyl)propane (TMBPA), to circumvent adverse effects of BPA. However, their increasing use is also contaminating the environment, which is a potential cause of concern for human health. Thyroid hormone transport and signaling are potential targets for endocrine-disrupting activity of BPA analogs. Thyroxine-binding globulin (TBG) is the major carrier protein for thyroxine (T4) and triiodothyronine (T3) in blood. Thyroid hormones exert their action through thyroid hormone receptors (TRα and TRβ). This report presents the thyroid-disrupting potential of indicated nine BPA analogs from structure-based studies with TBG and TRα. Each BPA analog formed important polar and hydrophobic interactions with a number of residues of TBG and TRα. Majority of TBG residues (77–100%) and TRα residues (70–91%) interacting with BPA analogs were common with those of native ligands T4 and T3, respectively. Majority of BPA analogs interacted with TBG forming a salt bridge interaction at Lys-270. The hydrogen-bonding interaction of T3 with TRα at His-381 was also shared by majority of analogs. The binding energy for BPP, BPB, BPZ, BPAP, and TMBPA with both proteins was closer to binding energy of respective native ligands. The similarity in structural binding characteristics suggested potential disrupting activity of thyroid hormone signaling and transport.

Chlorpyrifos (CPF) and aflatoxin B₁ (AFB₁) are each known to adversely affect hepatic tissue individually, but their combined hepatic effects have never been previously investigated. HepG2 cell viability, oxidative status, and genetic impairment were examined after exposing HepG2 cells to: (1) CPF alone, (2) AFB₁ alone, and (3) CPF and AFB₁ combined (20:1). CPF exposure decreased cell viability, reduced glutathione (GSH) content, and superoxide dismutase (SOD) activity but increased both glutathione peroxidase (GPx) and paraoxonase 1 activity. AFB₁ exposure decreased cell viability and GSH content but increased reactive oxygen species (ROS) production. CPF and AFB₁ combined exposure decreased GSH content (p < 0.05) further over individual CPF and AFB₁ exposures. Induction of micronucleus formation was detected in AFB₁-treated cells but undetected in both CPF and combination-treated cells. In conclusion, cytotoxic effects caused by combined exposure were antagonistic, as shown by a combination index value of 1.67. Although no change in ROS production was observed in CPF groups, the overall results confirmed the occurrence of oxidative stress through the alterations of GSH content, GPx, and SOD activity. Only intracellular GSH was evidently changed upon exposure to CPF and AFB₁ combined. Thus, this study suggested cellular GSH as a potential indicator for detecting the combined effects of CPF and AFB₁ in HepG2 cells, the detection of which could be adapted to estimate the potential toxicity of additional multiple toxicant exposures.

Lead is a nonessential metal which enters the body through various means and is considered as one of the most common health toxins. Several cases of lead poisoning are reported as a result of inhalation or ingestion of lead in employees working as painters, smelters, electric accumulator manufacturers, compositors, auto mechanics, and miners. In addition to occupational lead exposure, several cases of lead poisoning are reported in the general population through various sources and pathways. Innumerable signs and symptoms of lead poisoning observed are subtle and depend on the extent and duration of exposure. The objective of this review article is to discuss occupationally and nonoccupationally exposed lead poisoning cases reported in India and the associated symptoms, mode of therapy, and environmental intervention used in managing these cases. Lead poisoning cases cannot be identified at an early stage as the symptoms are very general and mimic that of other disorders, and patients might receive only symptomatic treatment. Knowledge about the various symptoms and potential sources is of utmost importance. Medical practitioners when confronted with patients experiencing signs and symptoms as discussed in this article can speculate the possibility of lead poisoning, which could lead to early diagnosis and its management.

The purpose of this study was to evaluate the potential influence of occupational ionizing radiation (IR) exposure on health professionals, assessing DNA damage using the comet and micronucleus (MN) assays and analyzing relative risks, correlations, and associated factors between outcomes and socioeconomic and lifestyle factors. Blood and buccal samples were collected from 36 workers, who actively participated in an imaging sector of a hospital, who were either exposed to IR directly or indirectly (9 internal control and 27 exposed), and 27 individuals living in the same city but with no occupational exposure (external control, unexposed/healthy). All radiation dosages performed on the 36 workers were less than 20 mSv/y, not exceeding the effective dose limit for occupational exposure. A questionnaire identified socioeconomic and lifestyle factors associated with the outcomes. The results of the MN assay showed a significant difference between both internal control and the exposed group when compared to the external control. For the comet assay, there were significant differences between the percent of tail DNA of the exposed group and external controls, but no difference was found between the exposed group and internal controls. Relative risk associations were found in time of exposure, hours worked per week, and perceived stress. Correlations were found between the outcomes and age, consumption of alcohol, and frequencies of X-rays during life. Variables that showed to be significant in the adjusted analysis were skin color and recent exposure to radiation. Albeit limited, the findings of this study suggest genotoxicity in both blood and buccal mucosa cells of workers exposed directly or indirectly to IR and that lifestyle and socioeconomic factors are associated and correlated with the risk of developing these outcomes.

The main aim of this cross-sectional study was to evaluate work-related injuries (WRI) and the self-reported musculoskeletal symptoms among 742 railway track maintainers. The second aim of this study was to investigate the potential factors related to the prevalence of musculoskeletal disorders (MSDs) in track maintainers. This study also tried to do planning and implementing ergonomic intervention programs to improve track maintainer’s health. Modified Nordic questionnaires were administered to assess the prevalence of MSDs. Detailed posture analysis by rapid entire body assessment (REBA) method was performed to assess the risk level of concerned postures. The injury data for 12 months were collected by conducting a survey and personal interviews with the affected railway track maintainers. To assess the prevalence of MSDs, the odds ratio and 95% confidence interval were computed along with critical χ ² values. Analysis of variance was performed to determine significant differences between the MSD present and absent among the track maintainers of the Indian railway. The result of this study showed that neglect of safety precautions is the main reason for injury, followed by slipping and falling and lack of awareness. Sprain injury is one of the main injuries, followed by cut, snakebite, abrasion, and fracture. Low educational levels of workers are also reasons for WRI. In conclusion, the prevalence and severity of MSD, particularly in the low back, knees, wrist, and shoulder and WRI were found to be very high among the track maintainers. The recommendations of this research are ergonomic interventions, such as track maintainers proper training, following the National Institute of Occupational Safety and Health -recommended weight limit for manual material handling, modification in hand tools, job rotation, performing stretching exercise, and avoiding awkward and static posture are needed.

Hepatocarcinogens are agents that increase the incidence of liver cancer in exposed animals or humans. It is now established that carcinogenic exposures have a widespread impact on the transcriptome, inducing both adaptive and adverse changes in the activities of genes and pathways. Chemical hepatocarcinogens have also been shown to affect expression of microRNA (miRNA), the evolutionarily conserved noncoding RNA that regulates gene expression posttranscriptionally. Considerable effort has been invested into examining the involvement of mRNA in chemical hepatocarcinogenesis and their potential usage for the classification and prediction of new chemical entities. For miRNA, there has been an increasing number of studies reported over the past decade, although not to the same degree as for transcriptomic studies. Current data suggest that it is unlikely that any gene or miRNA signature associated with short-term carcinogen exposure can replace the rodent bioassay. In this review, we discuss the application of transcriptomic and miRNA profiles to increase mechanistic understanding of chemical carcinogens and to aid in their classification.