Method development and validation for determining 1,3-butadiene in human blood by gas chromatography-mass spectrometry and head-space gas chromatography.

To develop a simple, validated method for identifying and quantifying 1,3-butadiene (BD) in human blood by gas chromatography-mass spectrometry (GC-MS) and head-space gas chromatography (HS-GC). BD was identified by GC-MS and HS-GC, and quantified by HS-GC. The method showed that BD had a good linearity from 50 to 500 microg/mL (r > 0.99). The limits of detection and quantification were 10 microg/mL and 50 microg/mL, respectively. Both the intra-day precision and inter-day precision were < 6.08%, and the accuracy was 96.98%-103.81%. The method was applied to an actual case, and the concentration of BD in the case was 242 microg/mL in human blood. This simple method is found to be useful for the routine forensic analysis of acute exposure to BD.

Method development and validation for determining 1,3-butadiene in human blood by gas chromatography-mass spectrometry and head-space gas chromatography / 法医学杂志

To develop a simple, validated method for identifying and quantifying 1,3-butadiene (BD) in human blood by gas chromatography-mass spectrometry (GC-MS) and head-space gas chromatography (HS-GC). BD was identified by GC-MS and HS-GC, and quantified by HS-GC. The method showed that BD had a good linearity from 50 to 500 microg/mL (r > 0.99). The limits of detection and quantification were 10 microg/mL and 50 microg/mL, respectively. Both the intra-day precision and inter-day precision were < 6.08%, and the accuracy was 96.98%-103.81%. The method was applied to an actual case, and the concentration of BD in the case was 242 microg/mL in human blood. This simple method is found to be useful for the routine forensic analysis of acute exposure to BD.

Butadiene cancer exposure-response modeling: based on workers in the styrene-butadiene-rubber industry: total leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and chronic myelogenous leukemia.

Cox regression is used to estimate exposure-response models (with cumulative 1,3-butadiene (BD) ppm-years as the exposure metric) based on the most recent data and validated exposure estimates from UAB's study of North American workers in the styrene-butadiene-rubber industry. These data are substantially updated from those in USEPA's 2002 risk assessment. The slope for cumulative BD ppm-years is not statistically significantly different than zero for CML, AML, or, when any one of eight exposure covariates is added to the model, for all leukemias combined (total leukemia). For total leukemia, the EC(1/100,000) is approximately 0.15 BD environmental ppm and the corresponding unit risk factor is approximately 0.00007 per BD environmental ppm. The excess risk for CML is approximately 15-fold less than for total leukemia. The maximum likelihood estimates suggest that there is no excess risk for AML from cumulative BD ppm-years. For CLL, the slope is statistically significantly different than zero. The excess risk for CLL is approximately 2.5-fold less than for total leukemia. For both total leukemia and CLL, the slope is not statistically significantly different than zero when the exposure-response modeling is based on the person-years with cumulative BD ppm-years less than or equal to 300 ppm-years.

Influence of some detoxification enzyme polymorphisms on cytogenetic biomarkers between individuals exposed to very low doses of 1,3-butadiene.

OBJECTIVE: To evaluate the variation of some biomarkers related to the level of enzymatic activity dependent on the different polymorphisms. METHODS: We studied 27 butadiene-exposed workers and 37 controls using different biomarkers of the genotoxic effect. The genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism-polymerase chain reaction techniques; the subjects were assigned to a specific group based on the microsomal epoxide hydrolase (mEH) activity predicted by their genotype (low, intermediate, high). RESULTS: The studied biomarkers were not able to discriminate between exposed and control individuals, but sister chromatid exchange (SCE) and high frequency cells were influenced by smoking habits. Smokers having fast microsomal epoxide hydrolase activity showed higher SCE frequency (7.61) respect to those presenting intermediate (5.86) or slow (6.65) enzymatic activity. CONCLUSIONS: On the basis of these results, can we suppose the existence of an "intermediate genotype" advantage (at least for induction of SCE)?

The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine.

The importance of the isoform CYP2E1 of the human cytochrome P-450 superfamily of enzymes for occupational and environmental medicine is derived from its unique substrate spectrum that includes a number of highly important high-production chemicals, such as aliphatic and aromatic hydrocarbons, solvents and industrial monomers (i.a. alkanes, alkenes, aromatic and halogenated hydrocarbons). Many polymorphic genes, such as CYP2E1, show considerable differences in allelic distribution between different human populations. The polymorphic nature of the human CYP2E1 gene is significant for inter-individual differences in toxicity of its substrates. Since the substrate spectrum of CYP2E1 includes many compounds of basic relevance to industrial toxicology, a rationale for metabolic interactions of different CYP2E1 substrates is provided. In-depth research into the inter-individual phenotypic differences of human CYP2E1 enzyme activities was enabled by the recognition that the 6-hydroxylation of the drug chlorzoxazone is mediated by CYP2E1. Studies on CYP2E1 phenotyping have pointed to inter-individual variations in enzyme activities. There are consistent ethnic differences in CYP2E1 enzyme expression, mostly demonstrated between European and Japanese populations, which point to a major impact of genetic factors. The most frequently studied genetic polymorphisms are the restriction fragment length polymorphisms PstI/ RsaI (mutant allele: CYP2E1*5B) located in the 5'-flanking region of the gene, as well as the DraI polymorphism (mutant allele: CYP2E1*6) located in intron 6. These polymorphisms are partly related, as they form the common allele designated CYP2E1*5A. Striking inter-ethnic differences between Europeans and Asians appear with respect to the frequencies of the CYP2E1*5A allele (only approximately 5% of Europeans are heterozygous, but 37% of Asians are, whilst 6% of Asians are homozygous). Available studies indicate a wide variation in human CYP2E1 expression, which are very likely based on complex gene-environment interactions. Major inter-ethnic differences are apparent on the genotyping and the phenotyping levels. Selected cases are presented where inter-ethnic variations of CYP2E1 may provide likely explanations for unexplained findings concerning industrial chemicals that are CYP2E1 substrates. Possible consequences of differential inter-individual and inter-ethnic susceptibilities are related to individual expressions of clinical symptoms of chemical toxicity, to results of biological monitoring of exposed workers, and to the interpretation of results of epidemiological or molecular-epidemiological studies.

The social and psychological impact of the chemical contamination incident in Weston Village, UK: a qualitative analysis.

This paper contributes to the literature on community response to the announcement of well-established chemical contamination close to their homes. It describes a study of residents' views of chemical contamination on a close and long-standing community in the context of impacts on everyday life. This followed the discovery early in 2000 that houses in Weston Village, in the County of Cheshire, England, were contaminated by the chemical hexachlorobutadiene which was seeping from a sealed chemical waste quarry owned by Imperial Chemical Industries, one of the world's largest chemical companies. Qualitative methods were used for the study. A total of 23 people from the village were interviewed in 15 focused, semi-structured interviews. This study highlights the importance of attention to secondary, community-level and interpersonal-level health impacts in the face of epidemiological uncertainty.

Lymphohematopoietic cancers and butadiene and styrene exposure in synthetic rubber manufacture.

The described nested case-control study of lymphohematopoietic cancers occurring in a cohort of synthetic rubber production workers was conducted to determine the associations of these cancers with exposure to butadiene and styrene. Cases have been confirmed through hospital record review of 95 percent of the cancers. Exposures are based on measured values of the two chemicals from personal monitoring data in seven of the eight plants under study. The results indicate that the risk of leukemia increases with exposure to a time-weighted average butadiene measure. The odds ratio at only 1 ppm average butadiene exposure is 1.50 (95% CI 1.07, 2.10). Work in specific areas also contributes to the risk, possibly because these areas have not been completely characterized for differences in butadiene exposure. Hodgkins disease is also associated with butadiene exposure. Multiple myeloma, lymphosarcoma, and all lymphomas are associated with exposure to styrene. Since workers in this industry are apparently exposed to two carcinogenic agents, further effort must be made to distinguish the exposures to each chemical over time and to characterize their interrelationship with the risk of cancers of the lymphohematopoietic system.

Epidemiologic study of cancer mortality among chloroprene workers.

Both case-control and cohort studies were undertaken from July 1, 1969 to June 30, 1983 to ascertain whether exposure to chloroprene increases the risk of cancer. Fifty-five cases of cancer deaths were verified, 16 of which had histories of exposure to chloroprene ranging from 3 to 23 years (median 11 years) with a latent period of 8-27 years, except for one case of 3 years (median 12.5 years). Fifty-four pairs were obtained by matching the cancer deaths to noncancer deaths in accordance with strict requirements. The odds ratio for the paired data was 13, X2 = 8.64, P less than 0.005. The average age at death from cancer of workers exposed to chloroprene was 12.7 years younger than that of unexposed workers, t' = 2.98, P less than 0.001. The total cohort consisted of 1213 persons, among whom 149 (11.6%) had histories of exposure for over 25 years, 381 (31.5%) for over 20 years, and 852 (70.2%) for over 15 years. The SMR for the total cohort was 2.38 (P less than 0.01), and all SMRs for the high-exposure occupations were of significance (P less than 0.05 or P less than 0.01), in contrast to those of the low-exposure grups whose SMRs were low or zero. Thus, a dose-response relationship existed. Among the high-exposure occupations, maintenance mechanics seem to have the highest risk of cancers, and SMRs for liver, lung, and lymphatic cancers were significant in this group. These results suggested that chloroprene exposure increases the risk of developing cancer.

Mercapturic acid formation is an activation and intermediary step in the metabolism of hexachlorobutadiene.

14C-hexachlorobutadiene (HCBD), a mutagenic and nephrocarcinogenic pollutant, was administered by oral gavage of 100 mg/kg to female rats, and the radioactivity in 24 hr urine pooled. The average amount of radioactivity recovered in urine was 5.4% of the total 14C-activity ingested. Solvent extraction, high performance liquid chromatography (HPLC), radio gas chromatography and gas chromatography/mass spectrometry were used for separation and identification of metabolites. After solvent extraction and HPLC four fractions were separated containing 1%, 5%, 15% and 80% of radioactivity. In the 80% fraction one metabolite was identified after derivatization and comparison with the authentic compound as the mercapturic acid of HCBD (N-acetyl-S-1,1,2,3,4-pentachlorobutadienyl)-L-cysteine). The mercapturic acid accounts for 10% of the urinary 14C-activity. In a first attempt the mutagenic potential of the mercapturic acid was determined on Salmonella typhimurium TA 100 with and without metabolic activating S9 mix. In the presence of S9 mix the mercapturic acid exerts a strong mutagenic effect which proved to be about 80 times higher than that of HCBD. The results identify the formation of the mercapturic acid via direct glutathione conjugation as an activating and intermediary step in the metabolism of hexachlorobutadiene.

A hematology survey of workers at a styrene-butadiene synthetic rubber manufacturing plant.

A previous epidemiologic study of the U.S. rubber industry indicated that there has been an excess of leukemia and lymphoma mortality among hourly workers at one styrene-butadiene rubber manufacturing plant. This investigation was a combined industrial hygiene and hematology cross-sectional survey at the same plant. The objectives of the survey were to quantify exposure levels for styrene, butadiene, benzene and toluene, and to relate these levels to hematologic variation. Personal air samples and blood specimens were obtained from 157 production workers. All exposure levels for the four chemicals assayed were well below recommended standards. The higher mean styrene (13.67 ppm) and butadiene (20.03 ppm) concentrations were found in the Tank Farm area; in all other departments the mean levels for the four chemicals were less than 2 ppm. The Tank Farm workers had slightly lower levels of circulating erythrocytes, hemoglobin, platelets and neutrophils, and slightly higher mean corpuscular red cell volumes and neutrophil band counts than the other workers. Overall, in this population there was no pronounced evidence of hematologic abnormality, as determined from examination of peripheral blood.

Epidemiologic investigations of styrene-butadiene rubber production and reinforced plastics production.

The United States National Institute for Occupational Safety and Health (NIOSH) began an epidemiologic study of workers employed in the styrene-butadiene rubber (SBR) industry during 1976. This study was prompted by reports of relatively high numbers of leukemia deaths occurring within SBR production work populations. Simultaneous with the initiation of this investigation, the University of North Carolina released a report associating an excess risk of death due to hematopoietic and lymphatic malignancies among workers producing several synthetic rubbers, including SBR. This report presents NIOSH's preliminary mortality observations and a discussion of progress made on the analyses of contaminants found in two SBR production facilities. Currently, NIOSH is determining the feasibility of doing an epidemiologic study in the reinforced plastics industry. Interest in this study developed as part of an effort to determine health hazards associated with occupational exposure to styrene. Most of the technology for the reinforced plastics industry developed in the 1950s, and therefore this process represents a relatively new industry. This report also includes information on environmental conditions observed in the reinforced plastics industry and enumerates some of the complicating characteristics of this industry which increase the complexity of this study.