Abstract  Human health assessment information on a chemical substance is included in IRIS only after a comprehensive review of toxicity data by U.S. EPA health scientists from several program offices, regional offices, and the Office of Research and Development. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime Exposure) present the positions that were reached during the review process. Supporting information and explanations of the methods used to derive the values given in IRIS are provided in the guidance documents located on the IRIS website at http://www.epa.gov/ncea/iris/backgr-d.htm.

Abstract  Labor conditions of workers engaged in chloroprene rubber production are characterized by exposure to a complex of chemical compounds among which the leading part is played by chloroprene and products Of its interaction with hydroxyl radicals and atmospheric ozone. It was shown with certainty that the activity of creatine kinase and purine nucleoside phosphorylase decreases 2-fold as compared to the control in blood serum Of workers engaged in chloroprene synthesis. Changes in enzymes activity are not related to gender, age or length of service. Activity of serumal alanine aminotransferase (ALT) and aspartate aminotransferase(AST) did not revealed any changes in those workers.

Abstract  The toxicity data of pesticides were summarized and compared amongst different animal species and types of bioassays. These comparisons showed the expected inter-species and inter-bioassay variability. After quantitative and statistical analysis of these data, it was concluded that, on the average, a 2-year dog bioassay detected toxic responses at similar doses as a 2-year rat study, and that both of these bioassays detected toxic responses at lower doses than either a rat 2-generation bioassay, a rat developmental toxicity study, or a 2-year mouse bioassay. Although these chronic dog and rat bioassays were found to detect toxic responses at lower doses than the other studies listed, this analysis does not reflect the seriousness of the effects that were compared. Within the confines of this analysis, then, it appears that a 2-year dog and rat study, reproductive and developmental bioassays are a sufficient data base on which to estimate high confidence Reference Doses (RfDs), and furthermore, that an additional uncertainty factor is needed to estimate RfDs to account for this inter-species and inter-bioassay variability when fewer than this number of bioassays are available.

Abstract  β-Chloroprene (CD), the 2-chloro derivative of 1,3-butadiene, is used for the manufacture of the synthetic rubber, polychloroprene. Acute inhalation studies show that CD is lethal to Crl:CD® rats at >2300 p.p.m. (4 h); the primary target organ effects were pulmonary hemorrhage and edema, and hepatic necrosis. In 2- and 4-week inhalation studies in Fischer 344 (F344) and Wistar rats, early deaths occurred at 500 and ≥161 p.p.m., respectively. Organ system injury was found in the nose (degeneration/metaplasia of olfactory epithelium), liver (centrilobular necrosis), and blood (decreased red blood cell count in F344 rats only). In a 90-day inhalation study with F344 rats, degeneration/metaplasia of the olfactory epithelium and reduced nonprotein sulfhydryl content of lungs and liver were found in animals exposed to 80 p.p.m., and anemia, hepatocellular necrosis, and forestomach inflammation were observed at 200 p.p.m. In a 90-day study with B6C3F1 mice, CD caused deaths at 200 p.p.m., the highest concentration tested, and epithelial hyperplasia of the forestomach at 80 p.p.m. Other than a slight (<10%) reduction in sperm motility in male rats at 200 p.p.m., all other reproductive parameters (sperm count or morphology in males, and estrous cyclicity or cycle length in females) were unaffected in these 90-day rat/mouse studies. There were no significant indications of neurological toxicity. The study No-Observable Adverse Effect Level was 32 p.p.m. based on nasal injury in rats. Despite some early reports of reproductive system abnormalities at levels <1 p.p.m., recent studies show no embryotoxic or developmental toxicity in female Wistar or Crl:CD® rats, or in New Zealand White rabbits at CD exposure concentrations up to 25 or 175 p.p.m., respectively. In a one-generation reproduction study with Wistar rats, CD produced growth retardation in the F0 generation exposed to 100 p.p.m., and in the F1 offspring at 33 and 100 p.p.m.; no effects on reproductive parameters or histopathology were found. CD is nonmutagenic in standard plate incorporation bacterial reverse mutation assays (Ames assays) but positive using direct gas-phase incubation methods. Bacterial mutagenicity (primarily base pair substitution) was either negative or weakly positive when freshly prepared CD was tested. Mutagenicity increased markedly with time, presumably from CD dimer formation, and also by addition of liver S9 metabolic activation system. In vivo micronucleus, chromosome aberration and sister chromatid exchange studies in mice showed no structural chromosomal damage. Overall, the pathological effects in the liver and nose dominate the subchronic toxicity of CD. The genotoxicity of CD is inconsistent and requires further study.

Abstract  PURPOSE AND OVERVIEW Data Quality Assessment (DQA) is the scientific and statistical evaluation of data to determine if data obtained from environmental data operations are of the right type, quality, and quantity to support their intended use. This guidance demonstrates how to use DQA in evaluating environmental data sets and illustrates how to apply some graphical and statistical tools for performing DQA. The guidance focuses primarily on using DQA in environmental decision making; however, the tools presented for preliminary data review and verifying statistical assumptions are useful whenever environmental data are used, regardless of whether the data are used for decision making.

Abstract  The U.S. Environmental Protection Agency (USEPA) recently proposed new guidelines to update and replace the 1986 USEPA Guidelines for Carcinogen Risk Assessment. Today, there is a better understanding of the variety of modes by which carcinogens can operate that did not exist when the 1986 USEPA guidelines were published. Many laboratories are adding new test protocols in their programs directed at questions concerning the mechanisms of action of carcinogens. In response to the evolving science of carcinogenesis, the new guidelines provide an analytical framework for incorporating all relevant biological information and recognizing a variety of situations regarding cancer risk. In addition, the guidelines are flexible enough to allow consideration of future scientific advances.

Abstract  Butadiene epidemiologic research has focused primarily on one cohort of workers in the North American styrene-butadiene rubber (SBR) industry and on the largest cohort of workers in the United States butadiene monomer industry. The most recent studies of these populations are characterized by carefully enumerated study populations, extremely long and high quality mortality follow-up, accurate job categorizations, detailed exposure assessments, and comprehensive statistical analyses. Leukemia was clearly associated with increasing estimated butadiene exposure in the SBR study, but not in the monomer industry study. This has lead to hypotheses about exposure differences between these two industries and the presence of co-factors or confounders in the SBR industry. Research presented at this symposium should shed some light on these hypotheses. The chloroprene epidemiologic literature, on the other hand, is in an early stage of development. The existing studies are limited by poor exposure characterization, lack of control of potential confounding factors, incompleteness in cohort enumeration, short follow-up periods, and small numbers of cancer cases. The state of the science for chloroprene would be advanced by arranging more comprehensive studies than those that have been conducted to date.

Abstract  We evaluated chromosomal aberrations in lymphocytes of 177 workers exposed to xenobiotics in a tire plant and in 172 controls, in relation to their genetic background. Nine polymorphisms in genes encoding biotransformation enzymes and nine polymorphisms in genes involved in main DNA repair pathways were investigated for possible modulation of chromosomal damage. Chromosomal aberration frequencies were the highest among exposed smokers and the lowest in non-smoking unexposed individuals (2.5+/-1.8% vs. 1.7+/-1.2%, respectively). The differences between groups (ANOVA) were borderline significant (F=2.6, P=0.055). Chromosomal aberrations were higher in subjects with GSTT1-null (2.4+/-1.7%) than in those with GSTT1-plus genotype (1.8+/-1.4%; F=7.2, P=0.008). Considering individual groups, this association was significant in smoking exposed workers (F=4.4, P=0.040). Individuals with low activity EPHX1 genotype exhibited significantly higher chromosomal aberrations (2.3+/-1.6%) in comparison with those bearing medium (1.7+/-1.2%) and high activity genotype (1.5+/-1.2%; F=4.7, P=0.010). Both chromatid- and chromosome-type aberration frequencies were mainly affected by exposure and smoking status. Binary logistic regression analysis revealed that frequencies of chromatid-type aberrations were modulated by NBS1 Glu185Gln (OR 4.26, 95%CI 1.38-13.14, P=0.012), and to a moderate extent, by XPD Lys751Gln (OR 0.16, 95%CI 0.02-1.25, P=0.081) polymorphisms. Chromosome-type aberrations were lowest in individuals bearing the EPHX1 genotype conferring the high activity (OR 0.38, 95%CI 0.15-0.98, P=0.045). Present results show that exposed individuals in the tire production, who smoke, exhibit higher chromosomal aberrations frequencies, and the extent of chromosomal damage may additionally be modified by relevant polymorphisms.

Abstract  TLV Recommendation There are marked disparities between the dose-response and reported effects from studies reported by U.S. and Russian investigators of the toxicity and hazards posed by exposure to chloroprene. The weight of both human and animal evidence for the carcinogenicity of chloroprene and for teratogenic and reproductive ef¬fects has to be considered as very limited or inadequate. The TLV Committee recommends aTLV-TWA of 10 ppm with a skin notation, based on the conclusion by von Oettingen and co-workers*4) that chloroprene probably can be absorbed through the skin in amounts sufficient to elicit acute effects. This TLV will protect exposed workers against the risk of systemic health effects. The TLV of 10 ppm for chloroprene Is equivalent to the TLV for 1,3-butadiene, a nonchlorinated analog of chloroprene. At this time, no STEL is recommended until additional toxicological data and industrial hygiene experience become available to provide a better base for quantifying on a toxicological basis what the STELshould be. The reader is encouraged to review the section on Excursion Limits in the "Introduction to the Chemical Substances" of the current TLV/BEI Booklet for guidance and control of excursions above the TLV-TWA, even when the 8-hour TWA is within the recommended limits.

Abstract  A cohort of 820 men in a Paterson, New Jersey, amosite asbestos factory which began work during 1941-1945 was observed from 5 to 40 years after start of work. Most of the cohort had limited duration of work experience (days, weeks, months), though some men worked for several years until the factory closed in 1954. With white males of New Jersey as the control population, Standardized Mortality Ratios (SMRs) of 500 are evident for the cohort for lung cancer and for noninfectious pulmonary diseases (including asbestosis), while being almost 300 for total cancer and about 170 for all causes of death. A statistically significant SMR of almost 200 is seen for colon-rectum cancer. Mesothelioma incidence initially shows a strong relationship with advancing time since onset of exposure and then tails off. The main concern of the study is with dose-response patterns. Response is measured by the mortality for relevant causes of death, while the direct asbestos dosage was measured in two ways. One way was the length of time worked in the factory and the other was the individual's accumulated fiber exposure, calculated by multiplying the aforementioned length of time worked by the estimated fiber exposures associated with the particular job that the worker had in the factory. Whichever measure of dosage is used, it was found that, in general, the lower the dose, the longer it took for adverse mortality to become evident and, also, the smaller the magnitude of that adverse mortality.

Abstract  This paper focused on the comparative evaluation of cure characteristics and mechanical properties of blends of natural rubber with dichlorocarbene modified styrene-butadiene rubber and chloroprene rubber with different blend composition. It was found that the Mooney scorch time and cure index shows a negative deviation from the calculated value based on the interpolation between the two component elastomers. However for the blends, modulus and hardness show a positive deviation. The mechanical properties of NR/DCSBR blend are higher than that of NR/CR blends. Flammability, oil and ozone resistance of the blend showed that as the NR content in the blend increases these properties were decreases and also NR/DCSBR blend showed excellent thermal, oil and ozone resistance than that of NR/ CR in entire blend ratios. The mechanical properties, modulus and hardness were also investigated after oil immersion. The changes in mechanical properties were correlated with variation in cross-link density estimated from stress-strain and swelling behavior. (C) 2004 Elsevier B.V. All rights reserved.

Abstract  Research has shown that workers employed in footwear manufacture are at increased risk of some cancers, the strongest evidence being for nasal cancer and leukemia. Footwear-workers are routinely exposed to complex mixtures of solvents in degreasers, cleaners, primers, and adhesives used in the production process as toluene, n-hexane, acetone, and possibly dust particles, additives in shoe materials and degradation products of materials. The recognition of the potential health-hazards of solvent-based adhesives (SBAs) has lead to the development of adhesives with no organic solvents, the water-based adhesives (WBA). We investigated footwear-workers (all males) exposed to SBA (n = 29) (for 3.98 +/- 4.13 years), and WBA (n = 16), which had spent the six months previous to the study employed in an experimental section which used only water-based adhesives, although they had previously worked in sections which used solvent-based adhesives (for 5.80 +/- 4.03 years); 25 healthy subjects were used as controls. The Comet assay and the micronucleus test were used as endpoints, while the traditional parameters for assessing exposure to toluene in organic mixtures by measuring the concentration of urinary hippuric acid were also assessed. Our results showed a significantly lower mean concentration of hippuric acid in the control group than found in the SBA (P < 0.001) and WBA (P < 0.05) groups. The Comet assay results showed that there was a significant increase in the mean damage index for the SBA (P < 0.001) group in comparison to the WBA group and control (P < 0.05). For the micronucleus test in binucleated lymphocytes and exfoliated buccal cell, the three groups were not statistically different. Our study demonstrated that water-based adhesives are clearly a better option for safeguarding the health of footwear-workers, even with possibility of isocyanate presence, while the positive results observed in SBA group might be explained by chloroprene presence in the adhesive. (c) 2005 Published by Elsevier B.V.

Abstract  The changes in the current values of the reaction rate constants during the C-60 fullerene and polychloroprene ozonolysis in solution have been investigated. The reaction has been conducted in a bubble reactor and the respective k values were determined on the basis of continuous measurement of the ozone concentration in the gas phase at the reactor outlet, under conditions of constant values of the ozone concentration at the reactor inlet. An effect of decrease in the current values of the rate constant during the conversion of the respective double bonds has been observed. It has been determined that the decrease Of C-60 fullerene k values in the 0-70% region of conversions is about 56%. In the case of polychloroprene the reduction is 18% and 24% at degree of conversion of 70% and 90% correspondingly. The mechanism of these effects and their influence on the rate constants dependences on the degree of conversion of the respective sp(2) C-C bonds have been considered. A supposition about the dominant role of the chemical factors on reduction of the current k values of the C-60 fullerene and polychloroprene has been substantiated.

Abstract  Human health assessment information on a chemical substance is included in IRIS only after a comprehensive review of chronic toxicity data by U.S. EPA health scientists from several program offices, regional offices, and the Office of Research and Development. Sections I (Chronic Health Hazard Assessments for Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime Exposure) present the positions that were reached during the review process. Supporting information and explanations of the methods used to derive the values given in IRIS are provided in the guidance documents located on the IRIS website at http://www. epa.gov/iriswebp/iris/backgr-d.htm.