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Occupational Exposures and Reproduction
Published in Michele Kiely, Reproductive and Perinatal Epidemiology, 2019
Increases in fetal loss have been observed among couples where the male partner was exposed and the woman presumably unexposed. Such associations have been reported for several agents: vinyl chloride and its structural analog chloroprene, lead, DBCP, anesthetic gases, and some work settings (a waste water treatment plant and a smelter).56 However, most of these associations derive from a single study and require replication before being accepted. Moreover, in most of these investigations, the obstetric history was obtained from the male worker rather than his wife and therefore may be inaccurate, particularly with regard to the number of miscarriages.56
Extraction and Chemistry of Rubber Allergens
Published in Robert N. Phalen, Howard I. Maibach, Protective Gloves for Occupational Use, 2023
Neoprene (polychloroisoprene, polychloroprene) is another type of rubber used for making gloves that can cause ACD. A variety of accelerators and additives have been reported to be used in the production of neoprene rubber products, including DTCs and thioureas. Warshaw et al.28 reported in a retrospective cross-sectional data study that gloves were the most common source of dialkylthioureas in cases of occupational ACD. Ramzy et al.43 heated chloroprene material in vials at 37°C and extracted the headspace vapor using solid phase microextraction Carboxen-PDMS fibers. The fibers were desorbed in the GC/MS injection port. Diethylthiourea (DETU), dibutylthiourea (DBTU), diphenylthiourea (DPTU), and their respective isothiocyanate breakdown products were assessed. Multiple neoprene products were assayed, but only one single diving sports glove was included in this study. It was concluded that DETU and ethylisocyanate were commonly found in chloroprene materials. In another study, DETU, DBTU, and ethylbutylthiourea were found in an acetone extract of a knee brace used by a thiourea patch-test positive gardener by the previously described HPLC ZDTC method.40 Even though neoprene surgical and exam gloves are commercially available, residual thioureas in these gloves have not been measured. Siegel et al.44 extracted four different surgical and exam neoprene gloves using dichloromethane and found dehydroabietic (DHA, colophony) in all four gloves, but not a control polyisoprene surgical glove. Extracts were injected directly into a GC-MS for chemical identification and then quantified by GC-MS following derivatization with N-methyl-N-(trimethylsilyl)trifluoroacetamide and 1% trimethylchlorosilane. DHA is a known prohapten that can cause ACD, but its clinical relevance in neoprene glove ACD has not been established.
Nonparametric tests for stratified additive hazards model based on current status data
Published in Journal of Applied Statistics, 2020
Xiaodong Fan, Shi-shun Zhao, Qingchun Zhang, Jianguo Sun
Now we apply the proposed test procedure to a set of current status data arising from a 2-year tumorigenicity study conducted by the National Toxicology Program. The study consists of the groups of 100 male and female F344/N rats and B6C3F1 mice, and they were exposed to chloroprene at concentrations 0, 12.8, 32, or 80 ppm by inhalation, 5 days per week, for 2 years. Some animals experienced natural death during the study, and the others were sacrificed at the end of the study. Each animal was examined for the presence or absence of tumors in different organs at the death or sacrificed time. Therefore only current status data are obtained for the tumor onset time. In the following, we focus on the presence of a specific type of lung tumor, the Alveolar/Bronchiolar Adenoma (A/B A), and the animals in the 0 and 80 ppm dose groups. The objective of the study is to access the effects of the concentrations of chloroprene and gender on the tumor onset time of the animals.
Incorporation of in vitro metabolism data and physiologically based pharmacokinetic modeling in a risk assessment for chloroprene
Published in Inhalation Toxicology, 2019
Harvey J. Clewell, Jerry L. Campbell, Cynthia Van Landingham, Allison Franzen, Miyoung Yoon, Darol E. Dodd, Melvin E. Andersen, P. Robinan Gentry
Chloroprene (CAS # 126-99-8) is a highly volatile chlorinated analog of 1,3-butadiene that is used in the manufacture of polychloroprene rubber (Neoprene). A cancer risk assessment for chloroprene conducted by the USEPA (2010) calculated an inhalation unit risk (IUR) of 5 × 10−4 per µg/m3 based on tumor incidence data from female mice exposed to chloroprene for 2 years (NTP 1998; Melnick et al. 1999). The USEPA (2010) assessment used a default cross-species extrapolation approach based on chloroprene exposure concentration, despite strong evidence of quantitative differences in chloroprene metabolism in mice and humans that would have a significant impact on the calculated risk (Himmelstein, Carpenter, and Hinderliter 2004; Himmelstein, Carpenter, Evans, et al. 2004). The metabolism of chloroprene results in the formation of reactive epoxides that are considered to be responsible for its carcinogenicity in rodents (USEPA 2010).
Semiparametric regression of clustered current status data
Published in Journal of Applied Statistics, 2019
Yanqin Feng, Shurong Lin, Yang Li
In this section, we apply the proposed methodology to a real data set from a lung tumorigenicity study, which arises from a 2-year tumorigenicity study conducted by National Toxicology Program (NTP) and provided in NTP technical report (1998). In the study, groups of 50 male B6C3F1 mice were exposed to chloroprene at concentrations 0, 32, or 80 ppm by inhalation, 6 hours per day, 5 days per week for 2 years. Each mouse was examined once for various tumors in different organs when died. Some mice died naturally during the study, and those who survived at the end of study were sacrificed for examinations. At each examination time (