Development and application of UPLC-Q-Orbitrap HRMS methods for the determination of eight metabolites of p-chloronitrobenzene in human urine.

Accurate, reliable, and sensitive methods for the determination of eight metabolites of p-chloronitrobenzene (p-CNB) were developed based on ultra-performance liquid chromatography - quadrupole - orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). The free and conjugated forms of metabolites were determined before and after urine samples were hydrolyzed with acid. Subsequently, three solid phase extraction steps were used for concentration and purification. The calibration curves of the eight metabolites exhibited good linearity with an R2 of >0.999, and the precision was good as well, with the coefficient of variations of intra-day and inter-day being lower than 7.0 % and 8.5 %, respectively. Analytical accuracy for all metabolites varied within ranges of 76.0-102.9 %, and the limit of detection and limit of quantification of all the metabolites varied within ranges of 0.2-7.7 µg/L and 0.6-25.6 µg/L in human urine, respectively. In addition, the application potential of the proposed methods were evaluated by applying them to the determination of metabolites in the urine of workers exposed to p-CNB, and these results showed that these methods were accurate, reliable, and sensitive, which makes them an excellent choice for detecting the metabolites of p-CNB in the urine of exposed workers.

Impact of biomechanical exposure (job-exposure matrix 'MADE') and social support on return to work following occupational injuries.

OBJECTIVES: To identify the determinants that influence the outcome of the return to work (RTW) after occupational injuries. METHODS: We conducted a cross-sectional study at the National Health Insurance Fund of Tunisia among victims of occupational injuries. Individual and professional factors have been evaluated through a face-to-face questionnaire for ten months. Biomechanical exposure was estimated by the job-exposure matrix "MADE" and social support by the Social Support Scale. Along with descriptive statistics, we used bivariate analysis, binary logistic regression, and random forest. RESULTS: We included 199 injured workers aged 20-60 years (mean = 42.73; 79.9 % male).Of the 199 injured workers, 39.7 % had unsuccessful RTW. Low social support, biomechanical exposure, blue-collar workers, working long hours, and severe injuries were associated with an unsuccessful return to work. In the variable importance plot issued from the random forest model, low social support at work was the most important risk factor of an unsuccessful RTW, followed by MADE variables: repetitiveness and effort. CONCLUSION: Biomechanical exposure and social support are main influencers of the return-to-work process.

Artisanal Gem Mining in Brazil: Evaluation of Oxidative Stress and Genotoxicity Biomarkers.

This study was carried out in the district of Taquaral de Minas, in the municipality of Itinga, located in Jequitinhonha Valley, state of Minas Gerais, which is considered one of the largest yolk-producing regions in Brazil. Miners in gem extraction areas are prone to severe oxidative damage due to their increased exposure to toxic metals, as well as chemical, physical, and biological agents, resulting in diseases such as silicosis. Thus, this work aimed to evaluate occupational exposure in prospectors through biomonitoring techniques using a variety of biomarkers for oxidative stress, genotoxicity, and mutagenicity. Twenty-two miners and seventeen workers who were not occupationally exposed were recruited, totaling thirty-nine participants. The study was approved by the Research Ethics Committee of the Federal University of the Jequitinhonha and Mucuri Valleys. In this study, the levels of total peroxides, catalase activity, and microelements in plasma were evaluated. Additionally, environmental analysis was carried out through the Ames and Allium cepa tests. The results of the lipoperoxidation assessment were significant, with increased frequencies in exposed individuals compared to controls (p < 0.05), as determined by the Mann-Whitney test. Micronutrients in the blood showed lower concentrations in the group exposed to Fe and Se than in individuals not exposed to these elements. The results of the Ames test and Allium cepa test were statistically significant compared to the controls (p < 0.05), as determined by the Mann-Whitney test for genotoxicity and cytotoxicity. Thus, the results of the present study indicate possible environmental contamination and a potential risk to the health of miners, which suggests that further studies are important in the region.

Longitudinal changes in cardiovascular disease-related proteins in welders.

OBJECTIVE: Occupational exposure to welding fumes is linked to a higher risk of cardiovascular disease; however, the threshold exposure level is unknown. Here, we aimed to identify changes in proteins associated with cardiovascular disease in relation to exposure to welding fumes. METHODS: Data were obtained from two timepoints six years apart for 338 non-smoking men (171 welders, 167 controls); of these, 174 (78 welders, 96 controls) had measurements available at both timepoints. Exposure was measured as personal respirable dust (adjusted for personal protective equipment), welding years, and cumulative exposure. Proximity extension assays were used to measure a panel of 92 proteins involved in cardiovascular processes in serum samples. Linear mixed models were used for longitudinal analysis. The biological functions and diseases related to the identified proteins were explored using the Ingenuity Pathway Analysis software. RESULTS: At both timepoints, the median respirable dust exposure was 0.7 mg/m3 for the welders. Seven proteins were differentially abundant between the welders and controls and increased incrementally with respirable dust: FGF23, CEACAM8, CD40L, PGF, CXCL1, CD84, and HO1. CD84 was significant after adjusting for multiple comparisons. These proteins have been linked to disorders of blood pressure, damage related to clogged blood vessels, and chronic inflammatory disorders. CONCLUSION: Exposure to mild steel welding fumes below current occupational exposure limits for respirable particles and welding fumes in Europe and the US (1-5 mg/m3) was associated with changes in the abundance of proteins related to cardiovascular disease. Further research should evaluate the utility of these proteins as prospective biomarkers of occupational cardiovascular disease.

[Status of occupational exposure limits of air toxic substances in the GESTIS Substances Database].

Objective: In order to understand the current situation of air toxic substances without occupational exposure limits (OELs) in the workplace in the Germany GESTIS Substance Database, and to provide an effective reference for formulating OELs of corresponding toxic substances and improving health standards. Methods: From March 2022 to May 2023, based on the standard of GBZ 2.1-2019 Occupational Exposure Limits for Hazardous Agents in the Workplace-Part 1: Chemical Hazardous Agents, air toxic substances without OELs in the standard of GBZ/T 300.1-2017 Determination of Toxic Substances in Workplace Air-Part 1: General Principles were screened out, then corresponding OELs in other countrie/regions were queried through the Germany GESTIS Substance Database. Results: Among the 333 kinds (classes) of air toxic substances in 160 parts of GBZ/T 300.1-2017 standard, 48 kinds (classes) of air toxic substances were screened out and had not yet been formulated OELs in GBZ 2.1-2019 standard. By querying the Germany GESTIS Substance Database, it was found that among the 48 kinds (classes) of air toxic substances, 35 kinds (classes) of air toxic substances had both 8-hour occupational exposure limit and short-term occupational exposure limit, 4 kinds (classes) of air toxic substances had 8-hour occupational exposure limit but no short-term occupational exposure limit, 9 kinds (classes) of air toxic substances hadn't been retrieved any OELs. In addition, standard test methods of 7 kinds of air toxic substances hadn't been published in the present, including trimethylchlorosilane, trimethylbenzenes, cumene, chloroethane, chloropropane, dibromoethane and acetophenone. Conclusion: In the process of formulating or revising the standards of GBZ 2.1-2019 and GBZ/T 300, the latest published OELs in the Germany GESTIS Substance Database could be used as a reference basis.

Use of micronucleus cytome assays with buccal cells for the detection of genotoxic effects: A systematic review and meta-analysis of occupational exposures to metals.

Micronucleus (MN) assays with buccal cells are at present widely used to investigate occupational exposures to genotoxic carcinogens. This article describes their use for the monitoring of metal exposed workers. We found in total 73 relevant articles, in the majority (97 %) increased MN and/or other nuclear anomalies were reported. Most studies were realized in South East Asia and South America. A variety of different occupations was studied including welders, electroplaters, painters, workers in battery recycling and production, tannery workers, dental technicians, miners, workers in foundries and smelters, and also subjects working in waste recycling, glass, aluminum and steel production. In many investigations the effects increased with the duration of the working period. The quality of individual studies was evaluated with a quality score tool. The number of cells was in most studies sufficient and DNA-specific stains were used. However, many studies have shortcomings, e.g. they focused solely on MN formation and did not evaluate anomalies, which provide additional information about the stability of the genetic material and acute cytotoxic effects. Only 35 % of the investigations contain quantitative information about exposures to metals and other toxicants. In 6 of these studies, correlations were observed between the concentrations of specific metals (As, Pb, Cr, Cd) in body fluids and MN frequencies. Taken together, the available data indicate that the MN assay can be used to detect chromosomal damage in metal exposed groups; furthermore, it enables also comparisons between subgroups differing in regard to their exposure and allows an estimation of the efficiency of protective measures. The exposure of workers to metals is currently controlled with chemical analytical measurements only, MN assays with buccal cells could contribute to further improve the safety at workplaces as they reflect the biological consequences including synergistic and antagonistic interactions between toxicants.

Impact of the Endonaut® angio-navigation system on radiation exposure in endovascular aortic repair performed with mobile C-arms.

OBJECTIVE: Fusion imaging systems have proved to reduce radiation exposure mostly in hybrid rooms but reports with mobile C-arms are few. The aim of this study was to analyse the impact of the Endonaut® navigation system on radiation exposure in endovascular aneurysm repair (EVAR) performed with mobile C-arms. METHODS: All patients undergoing EVAR and/or iliac branched devices implantation between January 2016 and August 2022 were included. All procedures were performed with a mobile C-arm (Siemens Avantic® or GE Elite® until March 2018, Siemens Cios Alpha® thereafter). The Endonaut® navigation system has been used since January 2021. Two groups were therefore compared : before (control group) and after the use of Endonaut®. Radiation data including Dose Area Product (DAP) values, Air Kerma (AK) and fluoroscopy time (FT) were collected retrospectively. RESULTS: Overall, 153 patients were included: control group (CGr), n = 121; Endonaut® group (EnGr), n = 32. No significant difference was found between the two groups regarding demographic data. DAP values were significantly lower in the EnGr (38 Gy.cm2 ± 24) vs. the CGr (76 Gy.cm2 ± 51) (p<.05) despite a significantly higher number of complex procedures such as iliac branched devices (p<.05). AK values were not significantly different between the EnGr and the CGr (196 mGy ± 114 vs. 209 mGy ± 138) as well as FT (33 minutes ± 18 vs. 33 minutes ± 16). Technical success was 97% (31/32) in the EnGr vs. 96% (116/121) in the CGr (p=.79). The volume of contrast media was significantly lower in the EnGr (94 cc ± 41) vs. the CGr (143 cc ± 66) (p<.05). CONCLUSION: In this study, the use of the Endonaut® angio-navigation system when performing EVAR with mobile C-arms led to a radiation dose reduction without compromising technical success or procedural time.

Worker perspectives on improving occupational health and safety using wearable sensors: a cross-sectional survey.

Workplace exposure is an important source of ill health. The use of wearable sensors and sensing technologies may help improve and maintain worker health, safety, and wellbeing. Input from workers should inform the integration of these sensors into workplaces. We developed an online survey to understand the acceptability of wearable sensor technologies for occupational health and safety (OSH) management. The survey was disseminated to members of OSH-related organizations, mainly in the United Kingdom and the Netherlands. There were 158 respondents, with over half (n = 91, 58%) reporting current use of wearable sensors, including physical hazards (n = 57, 36%), air quality (n = 53, 34%), and location tracking (n = 36, 23%), although this prevalence likely also captures traditional monitoring equipment. There were no clear distinctions in wearable sensor use between the reported demographic and occupational characteristics, with the exception that hygienists were more likely than non-hygienists (e.g. safety professionals) to use wearable sensors (66% versus 34%). Overall, there was an interest in how sensors can help OSH professionals understand patterns of exposure and improve exposure management practices. Some wariness was expressed primarily around environmental and physical constraints, the quality of the data, and privacy concerns. This survey identified a need to better identify occupational situations that would benefit from wearable sensors and to evaluate existing devices that could be used for occupational hygiene. Further, this work underscores the importance of clearly defining "sensor" according to the occupational setting and context.

Low levels of potentially toxic elements in workers are associated with self-reported health outcomes.

Occupational exposure to toxic elements can adversely affect health. The current study evaluated blood concentrations of potentially toxic elements (PTE) including As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, and Zn in formal and informal workers. Additionally, the study investigated the associations between blood PTE concentrations and reported health outcomes in the study population. The exposed group included women engaged in informal jewelry welding within their homes in Limeira, São Paulo state, Brazil (n = 36) and men who worked at a steel company in Volta Redonda, Rio de Janeiro state, Brazil (n = 22). The control group comprised residents of the same neighborhoods as the workers but without occupational exposure to chemicals (n = 28 in Limeira; n = 27 in Volta Redonda). Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry (TQ ICP-MS) was used to determine PTE concentrations in blood samples. Glycemia, insulin, and lipid profile tests were performed. All participants completed questionnaires on household risk and reported morbidity. The blood concentrations of Cd, As, and Pb, as well as glycemia, were higher in informal workers than in control subjects. No significant differences were observed between formal workers and control subjects. A robust Poisson regression model, adjusted for variables suggested by a Directed Acyclic Graph, disclosed associations of blood lead and arsenic concentrations with the prevalence of neurological manifestations in Limeira. Blood lead levels > 2.6 µg dL-1 were associated with 2.3 times the prevalence of self-reported neurological manifestations (95 % CI: 1.17-4.58; p = 0.02) than lower blood lead concentrations. Furthermore, a positive association between blood cadmium concentrations and glycemia was observed. Informal occupational exposure to these elements may indicate an increased risk of developing diseases. Monitoring exposure and implementing interventions to reduce PTE exposure in the work environment represent significant steps toward prevention.

Occupational exposure to chrysotile in an asbestos cement factory in Kyrgyzstan.

OBJECTIVES: An increasing number of countries are banning the production and use of asbestos, in compliance with the ratification of the C162 Asbestos Convention and the Basel Convention, and in response to the call for its elimination in the ILO resolution and WHO reports on the health risks associated with asbestos. Nevertheless, several countries, including Kyrgyzstan, are still miners and/or manufacturers of asbestos. The main objective of the study is to assess the occupational exposure to chrysotile of workers engaged in a production facility of asbestos-cement products in Kyrgyzstan. METHODS: Monitored workers (n = 16, for a total of n = 18 samples) were divided into 3 "Similar Exposure Groups" (SEGs; SEG-1: asbestos loading; SEG-2; asbestos-cement mixing; SEG-3: cutting of asbestos-cement sheets) according to EN 689 standard. Samples were collected through personal sampling and subsequently examined by means of scanning electron microscope equipped with an energy-dispersive spectrometer for the compositional analysis of each fibre. The numerical concentration of airborne asbestos fibres was henceforward determined by dividing the number of fibres and the volume of sampled air (expressed in the number of fibres per millilitre of air: ff/ml). RESULTS: Investigated workers resulted to be exposed to chrysotile fibres. Results (GM ± GSD) outlined extremely high exposure levels for SEG-1 (2.2 ± 2.1 ff/ml) and SEG-3 (4.7 ± 1.6 ff/ml) workers and lower-but still relevant-exposure values for SEG-2 (0.91 ± 2.6 ff/ml) workers. CONCLUSIONS: The results obtained in this case study can help to document potentially critical situations of occupational exposure to asbestos that can still occur nowadays in low and middle-income countries where asbestos is still mined and processed.

[Breast cancer: Could we consider it as an occupational exposure disease?] / Cancer du sein : peut-on l'envisager comme une maladie professionnelle ?

OBJECTIVE: Breast cancer is the leading cancer in women in terms of incidence and mortality. The literature currently identifies several risk factors, some modifiable and others not. Because of its multifactorial nature, the combination of factors either increases or reduces the risk of cancer. Since 2004, the first commission's rapport of the French National Environmental Health Plan has recognized the significant impact of occupational exposure on the development of breast cancer. However, neither primary nor secondary preventive measures have yet been implemented in work environment. METHOD: Based on available literature, we reviewed current knowledge of breast cancer risk factors associated with occupational exposure. RESULTS: The risk factors identified were ionizing radiation, magnetic fields, certain endocrine disruptors, ethylene oxide and night shift work. CONCLUSION: Recognition of breast cancer as an occupational disease is complicated. In some cases, however, it may be possible, particularly in cases of multifactorial exposure. This work should help to raise awareness among employers and reinforce preventive measures in the workplace.

The hospitalisation risk of chronic circulatory and respiratory diseases associated with coal mining in the general population in Queensland, Australia.

Queensland is the main coal mining state in Australia where populations in coal-mining areas have been historically exposed to coal mining emissions. Although a higher risk of chronic circulatory and respiratory diseases has been associated with coal mining globally, few studies have investigated these associations in the Queensland general population. This study estimates the association of coal production with hospitalisations for chronic circulatory and respiratory diseases in Queensland considering spatial and temporal variations during 1997-2014. An ecological analysis used a Bayesian hierarchical spatiotemporal model to estimate the association of coal production with standardised rates of each, chronic circulatory and respiratory diseases, adjusting for sociodemographic factors and considering the spatial structure of Queensland's statistical areas (SA2) in the 18-year period. Two specifications; with and without a space-time interaction effect were compared using the integrated nested Laplace approximation -INLA approach. The posterior mean of the best fit model was used to map the spatial, temporal and spatiotemporal trends of risk. The analysis considered 2,831,121 hospitalisation records. Coalmining was associated with a 4 % (2.4-5.5) higher risk of hospitalisation for chronic respiratory diseases in the model with a space-time interaction effect which had the best fit. An emerging higher risk of either chronic circulatory and respiratory diseases was identified in eastern areas and some coal-mining areas in central and southeast Queensland. There were important disparities in the spatiotemporal trend of risk between coal -and non-coalmining areas for each, chronic circulatory and respiratory diseases. Coalmining is associated with an increased risk of chronic respiratory diseases in the Queensland general population. Bayesian spatiotemporal analyses are robust methods to identify environmental determinants of morbidity in exposed populations. This methodology helps identifying at-risk populations which can be useful to support decision-making in health. Future research is required to investigate the causality links between coalmining and these diseases.

Impact of chlorpyrifos exposure on lung function in Egyptian adolescent agriculture workers.

Chlorpyrifos (CPF) is a widely used organophosphate insecticide that has been linked to detrimental health effects that range from neurological impacts to respiratory disease. The objective of this study was to assess respiratory symptoms associated with CPF exposure throughout the application season. Urine samples were collected from Egyptian adolescent applicators (n = 206) and non-applicators (n = 72) to assess 3,5,6-trichloro-2-pyridinol (TCPy), a biomarker for CPF exposure, along with spirometry measures to determine lung ventilatory function. Samples were collected over 7 months in 2016. Logistic regression was used to model the odds of reporting wheeze symptoms based on urinary TCPy concentrations while controlling for age and smoking in the household. Ordinal multinomial logistic regression was used to model the percent reference for forced expiratory volume in one second (rFEV1) based on urinary TCPy concentration (µg/g creatinine). Wheezing increased with increasing pesticide exposure (OR = 1.74 (1.32 - 2.31)). There was no statistically significant relationship between rFEV1 and TCPy concentration. Efforts to reduce pesticide exposure should be implemented to prevent the potential onset or exacerbation of any linked respiratory complications in adolescents.

Sick leaves among healthy pregnant Croatian healthcare workers during the COVID-19 pandemic due to loopholes in the occupational safety system.

The aim of this study was to explore occupational safety in pregnant Croatian healthcare workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic. To this end we composed an anonymous questionnaire that included pregnancy data, risk assessment and mitigation, and workplace intervention and distributed it to HCWs through social media of their groups and associations. The study includes a total of 173 respondents (71.1 % physicians, 19.7 % nurses, 9.2 % other HCWs) diagnosed with pregnancy in 2020 and 2021. Employers were notified about HCWs' pregnancy at the eighth (IQR 7.0-11.0) week of pregnancy, which delayed workplace risk assessment and mitigation beyond the first trimester. Only 19.6 % of the participants had the risk assessed and mitigated, mostly on their own initiative (76.5 %). After notifying employers about pregnancy, 37.0 % of participants opted for temporary work incapacity (TWI) due to "pregnancy complications" despite healthy pregnancy, 16.8 % were granted a pregnant worker's paid leave at the expense of the employer, while 5.8 % continued to work at the same workplace. Nurses used the TWI benefit more frequently than physicians (58.8 % vs 30.1 %, P=0.004). Our findings suggest that occupational safety of pregnant HCWs in Croatia lacks clear-cut and transparent strategies to protect pregnant HCWs, forcing them to misuse the healthcare system.

Infective SARS-CoV-2 in Skull Sawdust at Autopsy, Finland.

We assessed the distribution of SARS-CoV-2 at autopsy in 22 deceased persons with confirmed COVID-19. SARS-CoV-2 was found by PCR (2/22, 9.1%) and by culture (1/22, 4.5%) in skull sawdust, suggesting that live virus is present in tissues postmortem, including bone. Occupational exposure risk is low with appropriate personal protective equipment.

Development of a crosswalk to convert French PCS2003 into international ISCO88 occupational classifications. Application to the Occupational Asthma-specific Job-Exposure Matrix (OAsJEM).

INTRODUCTION: The problem of transcoding is recurrent when researchers wish to link occupational data from cohorts to Job-Exposure Matrices (JEMs) which were not set up in the same classifications. The Occupational Asthma-specific JEM (OAsJEM) is a JEM developed for assessing exposure to agents known at risk for asthma for jobs coded with ISCO88 occupation classification. To apply the OAsJEM in the CONSTANCES cohort, in which jobs and industries were coded with French PCS2003 and NAF2008 classifications respectively, we developed a crosswalk to convert jobs from PCS2003 into ISCO88 classification. METHODS: This work was carried out by 2 skilled coders and 1 novice coder who have worked independently by using different tools and transcoding strategies defined a priori. Consensus meetings were organized with skilled coders to define the final crosswalk. This work was elaborated in 2 steps: (i) for 38 ISCO88 codes classified as potentially exposed to cleaning and disinfection products by the OAsJEM, and (ii) for all jobs from the ISCO88 classification. A comparison between the 3 initial coder's crosswalk proposals and the final crosswalk was made for the 38 ISCO codes in step (i). RESULTS: The final crosswalk provided 998 matches between the 482 4-digit PCS2003 codes, 308 4-digit ISCO88 codes, and 31 3-digit ISCO88 codes. Information regarding the NAF2008 industry classification was also used in some cases to improve the final crosswalk. For the selected 38 ISCO88 codes, the final crosswalk provided 110 combinations, but the number of proposed ISCO88-PCS2003 couples by each of the 3 coders varied greatly from 68 to 153. In addition, an important variability between the 3 coders were observed among the number of common combinations between the initial coder's proposals and the final crosswalk (from 47% to 78%). DISCUSSION: We have developed a crosswalk specifically for an application of the OAsJEM in population-based surveys using the PCS2003 occupation classification. The development of this crosswalk is of great interest for the use of OAsJEM on the data of the CONSTANCES cohort and on any other survey with occupational data coded according to the French classifications. This OAsJEM crosswalk could be used by other teams to evaluate occupational exposures known to be at risk of asthma from occupational calendars coded with French classifications.

Development and validation of a quantitative wipe sampling method to determine platinum contamination from antineoplastic drugs on surfaces in workplaces at Swedish hospitals.

INTRODUCTION: Antineoplastic drugs (ADs) are frequently used pharmaceuticals in the healthcare, and healthcare workers can be occupationally exposed to ADs. Monitoring of surface contamination is a common way to assess occupational exposure to ADs. The objective was to develop and validate a sensitive and quantitative monitoring method to determine surface contaminations of Pt as a marker for Pt-containing ADs. The surface contaminations of Pt-containing ADs were monitored at four Swedish hospital workplaces. METHODS: An analytical method was developed based on inductively coupled plasma mass spectrometry. The wipe sampling procedure was validated regarding different surface materials. The stability of collected wipe samples was investigated. Workplace surfaces were monitored by wipe sampling to determine contaminations of Pt-containing ADs. RESULTS: A wipe sampling and analytical method with a limit of detection of 0.1 pg Pt/cm2 was developed. Pt was detected in 67% of the wipe samples collected from four workplaces, and the concentrations ranged from <0.10 to 21100 pg/cm2. In 4% of samples, the detected surface contaminations of Pt in three hospital wards were above proposed hygienic guidance value (HGV) of Pt. In the hospital pharmacy, 9% of the detected surface contaminations of Pt were above lowest proposed HGV. CONCLUSIONS: A user-friendly, specific, and sensitive method for determination of surface contaminations of Pt from ADs in work environments was developed and validated. A large variation of contaminations was observed between detected surface contaminations of Pt in samples collected in wards, and it likely reflects differences in amounts handled and work practices between the wards.

Bis-(2-Chloroisopropyl) ether.

Bis-(2-Chloroisopropyl) ether (BCIPE) was used as a solvent for fats, greases, paint, varnish removers, and in spotting and cleaning solutions. However, BCIPE has not been commercially manufactured or used for numerous years. In experimental animal studies, BCIPE is moderately toxic following acute oral, dermal, and inhalation routes of exposure. BCIPE is a severe eye irritant but not a dermal irritant or dermal sensitizer. BCIPE was not genotoxic or mutagenic in in vitro and in vivo assays; it was not toxic in a 3-generation reproductive dietary study in rats. Short-term, repeated inhalation and oral exposure in rats produced increased liver and kidney weights and congestion; dermal exposure in rabbits did not produce any observable adverse effects. BCIPE did not produce a statistically significant increase in tumors in two different 2-year dietary studies in mice and rats. In mice, technical grade BCIPE produced increased incidences of alveolar/bronchiolar adenomas in females, hepatocellular carcinomas in males, and a low incidence of forestomach hyperplasia (in both sexes at the high-dose). Further investigation with technical grade BCIPE concluded that these effects were species- and dose-specific with limited, if any, relevance to humans. The NOAEL of 400 ppm (15 mg/kg/day) from the 2-year dietary study in female rats was considered the point of departure for the health-based WEEL derivation. After adjustment for duration of exposure, interindividual variability, and intraindividual variability, an 8-h time-weighted average (TWA) WEEL value of 3 ppm (21 mg/m3) was derived. This exposure limit is expected to provide a significant margin of safety against any potential adverse health effects in workers.