Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “BUTADIENE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1997

Induction of micronuclei and sister chromatid exchange in mouse splenocytes after exposure to the butadiene metabolite 3,4-epoxy-1-butene.

3,4-Epoxy-1-butene (EB) is one of the main metabolites of 1,3 butadiene, a widely used industrial chemical. The mutagenic potential of 1,3 butadiene and its metabolites have been studied in different test systems. In this work the genotoxic effects of EB were studied by estimating micronuclei (MN) and sister chromatid exchange (SCE) frequencies in stimulated mouse splenocytes. Mice were treated in vivo with various doses of EB (24.4, 48.8 and 73.2 mg/kg). The antikinetochore antibody technique (CREST) was also applied to MN in cytokinesis blocked cells to investigate any possible aneugenic effect. Both MN and SCE frequencies increased after EB treatment. The induced MN resulted mainly from acentric fragments but a weak aneugenic effect was found as well. Cytotoxic effects of EB were observed at the highest dose. The above results, in combination with others on the effect of 1,3 butadiene and its metabolites in somatic and germ cells of mouse and rat as well as in somatic human cells, form a part of the information needed for application of the parallelogram approach and extrapolation to human risk.

Animals↗
PubMed2000

Inhibition of cytochrome P450 2E1 decreases, but does not eliminate, genotoxicity mediated by 1,3-butadiene.

1,3-Butadiene (BD), a rodent carcinogen, is metabolized to mutagenic and DNA-reactive epoxides. In vitro data suggest that this oxidation is mediated by cytochrome P450 2E1 (CYP2E1). In this study, we tested the hypothesis that oxidation of BD by CYP2E1 is required for genotoxicity to occur. Inhalation exposures were conducted with B6C3F1 mice using a closed-chamber technique, and the maximum rate of butadiene oxidation was estimated. The total amount of butadiene metabolized was then correlated with the frequency of micronuclei (MN). Three treatment groups were used: (1) mice with no pretreatment; (2) mice pretreated with 1,2-trans-dichloroethylene (DCE), a specific CYP2E1 inhibitor; and (3) mice pretreated with 1-aminobenzotriazole (ABT), an irreversible inhibitor of cytochromes P450. Mice in all 3 groups were exposed to an initial BD concentration of 1100 ppm, and the decline in concentration of BD in the inhalation chamber with time, due to uptake and metabolism of BD, was monitored using gas chromatography. A physiologically based pharmacokinetic model was used to analyze the gas uptake data, estimate V(max) for BD oxidation, and compute the total amount of BD metabolized. Model simulations of the gas uptake data predicted the maximum rate of BD oxidation would be reduced by 60% and 100% for the DCE- and ABT-pretreated groups, respectively. Bone marrow was harvested 24 h after the onset of the inhalation exposure and analyzed for frequency of micronuclei in polychromatic erythrocytes (MN-PCE). The frequency of MN-PCE per 1000 PCE in mice exposed to BD was 28.2 +/- 3.1, 19.8 +/- 2.5, and 12.3 +/- 1.9, for the mice with no pretreatment, DCE-pretreated mice and ABT-pretreated mice, respectively. Although inhibition of CYP2E1 decreased BD-mediated genotoxicity, it did not completely eliminate genotoxic effects. These data suggest that other P450 isoforms may contribute significantly to the metabolic activation of BD and resultant genotoxicity.

Administration, Inhalation↗
PubMed2003

Detection of carboxylic acids and inhibition of hippuric acid formation in rats treated with 3-butene-1,2-diol, a major metabolite of 1,3-butadiene.

Epidemiological studies have indicated that 1,3-butadiene exposure is associated with an increased risk of leukemia. In human liver microsomes, 1,3-butadiene is rapidly oxidized to butadiene monoxide, which can then be hydrolyzed to 3-butene-1,2-diol (BDD). In this study, BDD and several potential metabolites were characterized in the urine of male B6C3F1 mice and Sprague-Dawley rats after BDD administration (i.p.). Rats given 1420 micromol kg(-1) BDD excreted significantly greater amounts of BDD relative to rats administered 710 micromol kg(-1) BDD. Rats administered 1420 or 2840 micromol kg(-1) BDD excreted significantly greater amounts of BDD per kilogram of body weight than mice given an equivalent dose. Trace amounts of 1-hydroxy-2-butanone and the carboxylic acid metabolites, crotonic acid, propionic acid, and 2-ketobutyric acid, were detected in mouse and rat urine after BDD administration. Because of the identification of the carboxylic acid metabolites and because of the known ability of carboxylic acids to conjugate coenzyme A, which is critical for hippuric acid formation, the effect of BDD treatment on hippuric acid concentrations was investigated. Rats given 1420 or 2272 micromol kg(-1) BDD had significantly elevated ratios of benzoic acid to hippuric acid in the urine after treatment compared with control urine. However, this effect was not observed in mice administered 1420 or 2840 micromol kg(-1) BDD. Collectively, the results demonstrate species differences in the urinary excretion of BDD and show that BDD administration in rats inhibits hippuric acid formation. The detection of 1-hydroxy-2-butanone and the carboxylic acids also provides insight regarding pathways of BDD metabolism in vivo.

Animals↗
PubMed1985

Multiple organ carcinogenicity of 1,3-butadiene in B6C3F1 mice after 60 weeks of inhalation exposure.

Groups of 50 male and 50 female B6C3F1 mice were exposed 6 hours per day, 5 days per week, for 60 to 61 weeks to air containing 0, 625, or 1250 parts per million 1,3-butadiene. These concentrations are somewhat below and slightly above the Occupational Safety and Health Administration standard of 1000 parts per million for butadiene. The study was designed for 104-week exposures but had to be ended early due to cancer-related mortality in both sexes at both exposure concentrations. There were early induction and significantly increased incidences of hemangiosarcomas of the heart, malignant lymphomas, alveolar-bronchiolar neoplasms, squamous cell neoplasms of the forestomach in males and females and acinar cell carcinomas of the mammary gland, granulosa cell neoplasms of the ovary, and hepatocellular neoplasms in females. Current workplace standards for exposure to butadiene should be reexamined in view of these findings.

Air Pollutants, Occupational↗
PubMed2001

Assessment of 1,3-butadiene exposure in polymer production workers using HPRT mutations in lymphocytes as a biomarker.

1,3-Butadiene (BD), which is used to make styrene-butadiene rubber, is a potent carcinogen in mice and a probable carcinogen, associated with leukemia, in humans. We have previously used HPRT mutation as a biomarker to evaluate exposures to BD in a monomer production plant. We now report on a study of 49 workers in a styrene-butadiene rubber plant in which we used the concentration of the BD metabolite 1,2-dihydroxy-4-(N-acetylcysteinyl-S)-butane (M1) in urine as a biomarker of exposure and the frequency of HPRT variant (mutant) lymphocytes (Vf) as a biomarker of effect. Workers were assigned to high- and low-exposure groups based on historical information about work areas and jobs. Personal exposure to BD for one work shift was measured using a passive badge dosimeter. Each participant provided a urine specimen and blood sample at the end of the work shift and completed a questionnaire providing information on lifestyle, health, and work activities. The average BD exposures in the high- and low-exposure groups were significantly different, even after excluding two extreme values, (high 1.48 ppm; low 0.15 ppm, p < 0.002). This study was done in 1994 and 1995 before the establishment, in 1996, of the new permissible exposure limit of 1 ppm. Both the mean M1 and the HPRT Vf were more than three times greater in the high-exposure group than in the low-exposure group (p < 0.0005). The three end points correlated with each other, with sample correlation coefficients between 0.4 and 0.6. The correlations among BD exposure and the biomarkers of internal exposure and genotoxicity suggest that occupational exposure to BD, in the range of 1-3 ppm, may be associated with adverse biological effects.

Acetylcysteine↗
PubMed1990

Inhalation toxicity and carcinogenicity of 1,3-butadiene in Sprague-Dawley rats.

A 2-year inhalation study was conducted in Sprague-Dawley rats with 1,3-butadiene. Groups of 110 male and 110 female rats inhaled 1,3-butadiene at 0, 1000, or 8000 ppm for 6hr/day, 5 days/week. Interim clinical pathology, neuromuscular, and histopathology investigations were carried out. The study terminated at 20 to 25% survival (105 weeks for females, 111 weeks for males). Following exposure to 1,3-butadiene there were no effects on hematology, blood chemistry, urine analysis, and neuromuscular function that definitely could be associated with treatment. Treatment was associated with changes in clinical condition, suppression of body weight gain, reduced survival, and increases in certain organ weights and in both common and uncommon tumor types. Although the biological interpretation of the significance of some of the tumor types is equivocal, the evidence suggests that the test article is an oncogen to the rat under the conditions of exposure used in this study, and the mechanism is more likely to be an indirect effect through the endocrine system, rather than a direct effect through the production of reactive metabolites.

Air Pollutants, Occupational↗
PubMed1990

Results of NTP-sponsored mouse cytogenetic studies on 1,3-butadiene, isoprene, and chloroprene.

Studies were conducted to determine the cytotoxic and cytogenetic effects of 1,3-butadiene and two structural analogs, chloroprene and isoprene, in the bone marrow cells of B6C3F1 mice exposed to the chemicals by inhalation. In one study, animals were exposed to 1,3-butadiene concentrations of 6.25, 62.5, or 625 ppm 6 hr/day on 10 exposure days and in the second study, to the same concentrations on weekdays for 13 weeks. Chloroprene and isoprene treatments involved 6 hr/day exposures on 12 exposure days at concentrations of 0, 12, 32, 80, and 200 ppm for chloroprene and 0, 438, 1750, and 7000 ppm for isoprene. In the 10-day study, 1,3-butadiene induced significant increases in sister chromatid exchange (SCE) at 6.25 ppm, micronuclei at 62.5 ppm, and chromosomal aberrations at 625 ppm. In the 13-week study, the frequency of micronucleated normochromatic erythrocytes in the peripheral blood was significantly elevated in all exposure groups including the 6.25-ppm group. Isoprene induced both SCE and micronuclei, whereas chloroprene gave negative results for all cytogenetic end points assessed in bone marrow cells.

Animals↗
PubMed1990

Future directions--toxicology studies of 1,3-butadiene and isoprene.

Examination of a profile of data already existing on 1,3-butadiene shows adequate knowledge in many areas of toxicology that are conventionally required in hazard identification. However, while much progress has been made in areas of metabolism and pharmacokinetics, further studies would be worthwhile to improve mechanistic understanding such as the examination of alternate metabolic pathways, the generation of interspecies scaling factors, and an assessment of the relevance of various tumor sites. In this respect, data pertaining to repeated and pulse exposures of rodents and primates would be helpful. Another important aspect is the need to understand any human health implications of the observed 1,3-butadiene-induction of the murine leukemia virus. In this respect, studies have been pursued that include the comparison of leukemogenesis in congenetic strains, the leukemogenicity of viral isolates in rodent carcinogenicity and human cell culture studies, and the mechanisms of activation of ecotropic proviral sequences. Molecular epidemiological and toxicological research is ongoing in rodents and primates to evaluate hemoglobin adduct formation as an index of 1,3-butadiene exposure. Challenges of specificity, sensitivity, and simplification of current procedures need to be overcome. Recent mutagenicity and metabolism data suggest that structurally-related isoprene may have carcinogenic potential. The use of interstrain comparative studies and data in a second species is discussed, as well as proposed metabolism studies.

Animals↗
PubMed2006

Treatment of the butadiene washing stream from a synthetic rubber industry and recovery of p-TBC.

Butadiene is marketed containing p-tertbutylcatechol (p-TBC), a polymerization inhibitor that should be removed before butadiene utilization in synthetic rubber production. p-TBC can be removed from butadiene by washing with sodium hydroxide (NaOH) solution, producing a wastewater with pH 14, which contains high amounts of p-TBC, a toxic chemical compound. The aim of this work was to develop a treatment process that could reduce the content of p-TBC from the wastewater. Since p-TBC is very soluble in basic, but not in neutral and acid solutions, acidification tests were performed with phosphoric acid (H3PO4) to precipitate p-TBC. Reaction between NaOH and H3PO4 can result in crystallization of large amounts of salt without p-TBC precipitation. Under selected acidifying conditions p-TBC precipitates and the wastewater COD is highly reduced (> 90/o). Chromatographic determinations showed that the precipitated p-TBC could be recovered with 99% purity.

Butadienes↗
PubMed1982

Hepatic microsomal metabolism of 1,3-butadiene.

1. In rat liver microsomes, 1,3-butadiene was metabolized to butadiene monoxide, which was subsequently transformed into 3-butene-1,2-diol by microsomal epoxide hydrolase. 2. In the metabolism of butadiene oxide in microsomes, four metabolites were detected, namely two stereoisomers of DL-diepoxybutane, and two stereoisomers of 3,4-epoxy-1,2-butanediol. No meso-diepoxybutane was detected.

Animals↗
PubMed2000

Mutagenic potential of adenine N(6) adducts of monoepoxide and diolepoxide derivatives of butadiene.

To determine the biological effects of specific DNA adducts resulting from the interaction of 1,3-butadiene metabolites with DNA, deoxyoligonucleotides have been synthesized with four different adducts at the N(6) position of adenine, centrally located within the human N-ras codon 61. The adducts are those arising from adduction by either the R or S stereoisomer of the monoepoxide (BDO) or the (R,R) or (S,S) isomer of the diolepoxide (BDE). The diolepoxide can arise from partial hydrolysis of the diepoxide (BDO(2)) or from epoxidation of hydrolyzed monoepoxide. These adducted oligonucleotides were used in in vivo and in vitro assays designed both to determine their mutagenic potency and to examine specific interactions with Escherichia coli polymerases. Each adducted oligonucleotide was ligated into a single-stranded vector M13mp7L2 that was subsequently used to transfect E. coli. The resulting mutagenic spectrum for these modified DNAs was stereoisomer specific. Both monoepoxide lesions were nonmutagenic, but the mutagenic spectra for the modified DNAs containing BDE adducts were stereoisomer specific. The mutations generated by adducts of the R,R enantiomer of the diolepoxide were exclusively A --> G, whereas adducts of the S,S enantiomer of the diolepoxide yielded exclusively A --> C mutations. None of the four modifications resulted in significant blocks to in vivo phage replication, as evidenced by no decrease in plaque-forming ability. Consistent with these data, when each of three purified E. coli polymerases was used to replicate DNAs containing these adducted deoxyoligonucleotides, the individual polymerases appeared to be virtually unaffected, such that all lesions were readily bypassed. Whereas previous animal model studies identified the mutagenic spectrum related to butadiene exposure, these studies begin to establish the specific lesions responsible for mutagenesis. This is the first report of stereoselectivity related to butadiene-induced mutagenesis.

Adenine↗
PubMedDate not supplied

[A simple method for risk assessment and its application to 1,3-butadiene].

BACKGROUND: This paper presents a risk assessment exercise applied to 1,3-butadiene, a probable carcinogenic agent, in the context of the activity of the Scientific Committee on Occupational Exposure Limits (SCOEL) of the European Commission. Data on cumulative exposures and relative risks for leukaemia in humans were derived from the open literature. METHODS: A variety of excess relative risk models were applied taking into consideration, in a life-table fashion, mortality from leukaemia by age. RESULTS: As an example of the outcome of the method, results are presented for a 1 ppm exposure (each year) lasting for a working lifetime. They show that in a population of 1,000 adult males experiencing mortality rates similar to those of the 1981 male population of England and Wales, occupational exposure to 1 ppm of 1,3-butadiene for each year of a working life (40 years between the age of 20 and 65) will cause from 0 to 7.1 extra leukaemia deaths between the age 20-85 years, in addition to the 5.1 leukaemia deaths expected to occur in the absence of exposure to 1,3-butadiene. A summary of the estimates, in terms of excess leukaemia deaths, obtained for 0.1 ppm, 0.2 ppm, 0.5 ppm, 1.0 ppm, 2.0 ppm, 5.0 ppm, and 10 ppm of exposure (each year) is also presented. CONCLUSIONS: The method can be applied to predict the risk of carcinogenic agents for which dose-response data exist and no health-based limit value can be established. Results are consistent with those of previous risk assessments based on similar assumptions

Adult↗
PubMedDate not supplied

Identification of 1,3-butadiene, benzene, and other volatile organics from wok oil emissions.

As part of a program to determine the underlying factors responsible for genotoxicity and perhaps lung cancer risk in Chinese women, we qualitatively identified the volatile components emitted during the heating of cooking oils to 265 degrees C. 1,3-Butadiene, benzene, and a series of aldehydes, olefins, and saturated hydrocarbons were elucidated in vapors from Chinese rapeseed oil. On a relative basis, the intensity of 1,3-butadiene vapors from this were 15.7-, 6.3-, and 1.4-fold greater than in the vapors from peanut, soybean, and Canola oils, respectively. Thus, the Chinese rapeseed oil yielded a higher emission rate of 1,3-butadiene than the other three oils investigated. The benzene formation rate followed a similar trend, i.e., its intensity in Chinese rapeseed oil was 14-, 6.6-, and 1.7-fold greater than in vapors from peanut, soybean, and Canola oils, respectively.

Arachis↗
PubMed1993

Biological monitoring of 1,3-butadiene: species differences in haemoglobin binding in rat and mouse.

The adduct formed by the reaction of 1,3-butadiene monoxide, a major metabolite of the mutagen and carcinogen 1,3-butadiene, with the N-terminal valine of haemoglobin was used as a dosimeter for the bioavailability of reactive metabolites. The dose-dependence of adduct formation was studied in female CB6F1 mice and female Wistar rats exposed to 0, 50, 200, 500 or 1300 ppm butadiene in an open inhalation chamber for 6 h per day for five consecutive days. Globin was isolated 18 h after the last exposure, and N-terminal valine was obtained by a modified Edman degradation procedure. Adduct levels were five times higher in mice than in rats (17 and 3.5 nmol/g globin, respectively, at 500 ppm), which may partially explain the greater susceptibility of mice to tumour formation. Adduct levels increased linearly with dose in rats, whereas in mice this slope of the curve became flatter at 500 ppm and increased with higher doses. Similar results were obtained in male and female C3H x 101/EL mice.

Administration, Inhalation↗
PubMed1993

Male-mediated F1 effects in mice exposed to 1,3-butadiene.

We examined the effects on dominant lethality and the incidence of fetal abnormalities of acute and subchronic exposure of male mice by inhalation to the industrial monomer 1,3-butadiene. Investigation of the effect on tumour incidence in surviving offspring is still in progress. In the acute study, CD-1 mice were exposed to atmospheres containing 0 (n = 25), 1250 (n = 25) or 6250 ppm (n = 50) for 6 h, and each male was caged five days later for one week with two untreated virgin females. One of the females was killed humanely on day 17 of gestation. The other was allowed to deliver and rear her litter; the litters are being monitored for life. The killed female was examined for the number of live fetuses, the number of post-implantation deaths (early and late) and the number and type of any gross malformations. In the subchronic study, males were exposed to 0 (n = 25), 12.5 (n = 25) or 1250 ppm (n = 50) for 6 h per day on 5 days per week for 10 weeks and then mated immediately. Mating and observation were conducted as in the acute study. Acute exposure to butadiene resulted in only a small decrease in implantations; after 10 weeks' subchronic exposure to either the high or the low concentration, however, a wide variety of statistically significant effects was seen. At 1250 ppm, the number of implantations was reduced, dominant lethal mutations were induced, and the incidences of early and late deaths were increased; some of the live fetuses had abnormalities. The low dose also increased the frequency of abnormalities and late deaths, but it did not affect the number of early deaths. Thus, butadiene is mutagenic in the germ cells of male mice, as shown by the induction of dominant lethality at 1250 ppm, and the frequencies of late deaths and congenital abnormalities appear to be increased at the subchronic level of 12.5 ppm.

Abnormalities, Drug-Induced↗
PubMed1993

Genetic toxicity of 1,3-butadiene and styrene.

1,3-Butadiene and styrene (vinyl benzene) are indirect genotoxins, which require metabolic activation to an epoxide form in order to bind covalently to DNA. Styrene 7,8-oxide, the active metabolite of styrene, is a carcinogen in rodents and has been shown to be genotoxic in most in-vitro test systems and at various genetic endpoints. The few studies available on the genotoxicity of styrene 7,8-oxide in vivo have yielded negative or (in mice) weakly positive results. Styrene is not usually genotoxic in vitro in assays employing a microsomal preparation from rat liver for metabolic activation, but positive effects have been obtained when other sources of metabolic activation, such as human erythrocytes, were provided. In vivo, styrene has been found repeatedly to be weakly genotoxic in the assay for sister chromatid exchange, especially in mice. Cytogenetic damage (usually chromosomal aberrations) has been reported in many studies of workers, mainly from the reinforced plastics industry where ambient concentrations of styrene may be high (50-100 ppm), while most negative findings are associated with exposure to lower levels. Butadiene is metabolized to two reactive forms, 1,2-epoxy-3-butene and further to 1,2:3,4-diepoxybutane, both of which are genotoxic in various test systems in vitro. The lowest effective dose of the latter is 1-2 orders of magnitude higher than that of the respective monoepoxide. Butadiene itself has not been tested extensively for genotoxicity in vitro. A species-specific difference in the responses of mice and rats at various cytogenetic end-points is seen in vivo, the lowest effective concentrations in rats being clearly higher than those in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Mutagenicity of 1,3-butadiene and its epoxide metabolites in human TK6 cells and in splenic T cells isolated from exposed B6C3F1 mice.

The mutagenic potential of 1,3-butadiene and its epoxide metabolites have been measured in a human lymphoblastoid cell line (TK6) and in splenic T cells from exposed B6C3F1 mice. TK6 cells were exposed for 24 h to 0-400 microM 1,2-epoxybutene, 0-800 microM 3,4-epoxy-1,2-butanediol or 0-6 microM diepoxybutane and plated to measure the frequencies of mutations at the hprt and tk loci. All three metabolites were mutagenic at both loci, but diepoxybutane was active at concentrations 100 times lower than epoxybutene or epoxybutanediol. Mice exposed to 625 ppm butadiene for two weeks had an average hprt mutation frequency of 6.2 x 10(-6) in splenic T cells, whereas that in controls was 1.2 x 10(-6). In mice given three daily intraperitoneal doses of epoxybutene at 60, 80 and 100 mg/kg or diepoxybutane at 7, 14 and 21 mg/kg, the average hprt frequencies were 5.4, 4.1 and 8.6 x 10(-6) in those given epoxybutene and 4.6, 9.4 and 13 x 10(-6) in those treated with diepoxybutane. DNA sequencing revealed that 50% of the mutations induced in vivo by butadiene, epoxybutene and diepoxybutane were transition and transversion mutations at AT and GC base-pairs and 50% were frameshift mutations. The mutational spectra obtained are very similar to that produced by ethylene oxide, suggesting that these epoxides act through a similar mechanism.

Animals↗
PubMed1993

Industrial exposure to 1,3-butadiene in monomer, polymer and end-user industries.

Researchers from the National Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention conducted an extent-of-exposure study of 1,3-butadiene monomer, polymer and end-user industries to assess occupational exposure to butadiene and to evaluate control technologies. The findings of the exposure assessment are reported here. Walk-through surveys were conducted in 11 monomer, 17 polymer and two end-user plants; in-depth industrial hygiene surveys were conducted at four monomer, five polymer and two end-user plants. Airborne exposure concentrations of butadiene were determined for various job categories by personal sampling. The samples were analysed by a new method developed at NIOSH that is sensitive to 0.2 microgram per sample. A total of 687 personal (full-shift and short-term) and 232 area samples were taken. The results indicate that all exposures were well below the current permissible exposure limit of the US Occupational Safety and Health Administration of 1000 ppm. The US Occupational Safety and Health Administration (1990) has proposed a new standard that would reduce exposure to 2 ppm. Exposures ranged from less than 0.005 ppm to 374 ppm, and 3.7% of the samples contained more than 10 ppm, 7.8% more than 2 ppm but less than 10 ppm and 88.5% less than 2 ppm. We recommend means for reducing exposure by the use of engineering controls.

Air Pollutants, Occupational↗