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 199 records · Page 11Linked to original sources
PubMed1992

Butenes and butadiene in urban air.

Samples of urban air hydrocarbons were taken on specifically made adsorbent cartridges and analysed by gas chromatography after thermal desorption. The four isomeric butenes and 1,3-butadiene were favourably resolved and separated from the abundant alkanes on an aluminium oxide PLOT column. The concentrations of butadiene, reflecting outdoor urban exposure, were in the range of 0.5-5 micrograms/m3. An approximate 1:4 ratio was observed between butadiene and propene which both originate predominantly from vehicle exhaust. The four butenes made up approximately 50% of the propene concentration in exhaust-polluted air, with methylpropene greater than 1-butene greater than trans-2-butene greater than cis-2-butene. Petrol vapour contributed less than exhaust but about five times more to the 2-butenes than to methylpropene and 1-butene. The highest exposure levels of butadiene and butenes were consistently observed in the vicinity of exhaust pipes and petrol-fuelled vehicles.

Air Pollutants↗
PubMed1995

Heritable translocations induced by inhalation exposure of male mice to 1,3-butadiene.

Previously, we reported that dominant lethal mutations were induced in spermatids after inhalation exposure of male (102/El x C3H/El)F1 mice to 1300 ppm of 1,3-butadiene on 5 days for 6 h per day (exposure dose 39,000 ppm h). The same inhalation exposure was given to male C3H/El inbred mice which were mated to inbred line 102/El females 8-14 d after the end of exposure. Male and female F1 hybrid progeny were tested for the presence of heritable translocations by observation of litter sizes and by cytogenetic analyses in meiotic and somatic cells. 1,3-Butadiene induced heritable translocations in late spermatids. The translocation frequency after 1,3-butadiene exposure to 39,000 ppm h was 2.7% (16 translocation heterozygotes among 559 F1 offspring). This frequency is 54 times higher than the historical control frequency (0.05%; 5 translocation heterozygotes among 9500 F1 offspring). Thus, 1,3-butadiene causes heritable germ cell effects in mice.

Administration, Inhalation↗
PubMed1996

hprt mutation frequency among workers exposed to 1,3-butadiene in China.

Hypoxanthine-guanine phosphoribosyl transferase (hprt) mutation frequency (M(f)) was studied in workers at a polybutadiene rubber production facility in Yanshan, China. Exposed workers included for study were active either as process analysts, who sampled butadiene production process lines and analyzed product by gas chromatography, or as process operators, who did routine process control, minor maintenance and, as needed, major repair operations. For process analysts at the polymer and dimethyl formamide (DMF) facilities, the median air levels of BD were 1.0 and 3.5 ppm, respectively. Among process operators, air levels of 1.1 ppm were found during routine activities, while the median air level during pump repair and related operations was 45 ppm (6-h time-weighted average). Overall, M(f) was similar in unexposed (mean M(f) = 20.2 x 10(-6)) and butadiene-exposed (mean M(f) = 21.6 x 10(-6)) workers (P = 0.68). M(f) decreased with cloning efficiency, increased with age, and was moderately greater in women than in men. After adjustment by multiple regression analysis for mean age, sex, and cloning efficiency, the adjusted mean M(f)(Xadj) was 13.6 x 10(-6) in unexposed and 18.0 x 10(-6) in butadiene-exposed. This 32% difference was, however, not statistically significant (P = 0.13). Butadiene exposure was associated with a modest, if any, increase in hprt M(f) in this population of Chinese workers.

Adult↗
PubMed1996

Review of risk assessments on 1,3-butadiene (1985-1991).

During the past decade, several assessments have estimated the carcinogenic risk of inhaled 1,3-butadiene (BD) to the general population as well as for occupational exposures. Although most of the risk assessments have been based on inhalation bioassays in mice, some of the assessments have included the 2-year inhalation bioassay in rats. Because of the marked species differences in the carcinogenic response to butadiene, estimates of risk vary over nine orders of magnitude going from the most sensitive target organ in female mice to less sensitive male rats. An important tool in determining which estimate is most relevant for extrapolation to humans is to ascertain consistency with human experience. Estimated workplace cancer risks which are based on the assumption that humans are as responsive as the mouse suggest added risks of 200 or more out of 1000 workers (1 in 5) exposed to 2 ppm butadiene (assume 40 years of exposure). This estimate is clearly inconsistent with what has been seen and this would not have been missed in epidemiology studies. Risk assessments based on the growing understanding of the mechanisms of toxicity and the importance of various tissues ability to produce and maintain reactive epoxide metabolites demonstrate why rats are much less susceptible than the mouse. By developing a mechanistic understanding of humans, it is possible to refine the traditional approach to risk assessment, whereby better risk assessments can be made. This paper presents a summary of eight risk assessments that have been developed to date for butadiene.

Animals↗
PubMed1996

Risk assessment of butadiene in ambient air; the approach used in the UK.

The UK Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC) and the related Committee on Mutagenicity provided advice on 1,3-butadiene in 1992. This followed detailed consideration of the available mutagenicity, animal carcinogenicity and epidemiology data plus information on toxicokinetics. They concluded that 1,3-butadiene was an in vivo mutagen, a potent genotoxic animal carcinogen and should be regarded as a probable human carcinogen. The Department of Health is not aware of more recent data warranting reconsideration of these conclusions. General advice on setting air quality standards for carcinogenic air pollutants was given by the COC. Although the prudent assumption of the absence of any safe level for genotoxic carcinogens was preferred, a pragmatic approach based essentially on assessment of the exposure at which no increased risk would be detected, plus a safety factor, was considered reasonable for compounds like butadiene where exposure cannot be totally avoided. This approach, plus recognition that it is unadvisable to allow ambient levels of genotoxic carcinogens to rise, is used in the UK. The procedure by which the Department of Environment's Expert Panel on Air Quality Standards recommended a value of 1 ppb for butadiene based on these principles is described.

Air Pollutants↗
PubMed2006

Urinary biomarkers of 1,3-butadiene in environmental settings using liquid chromatography isotope dilution tandem mass spectrometry.

Although, 1,3-butadiene is a known human carcinogen emitted from mobile sources, little is known about traffic-related human exposure to this toxicant. This pilot study was designed to characterize traffic-related environmental exposure to 1,3-butadiene and evaluate its urinary mercapturic acids as biomarkers of exposure in these settings. Personal air samples and multiple urine samples were collected on two separate occasions from three groups of individuals that differed by spatial proximity as well as intensity of traffic: (i) toll collectors, (ii) urban-weekday and (iii) suburban-weekend group. Air samples were analyzed using thermal desorption followed by GC/MS and urine samples were analyzed using isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) for two mercapturic acids of 1,3-butadiene: monohydroxy-3-butenyl mercapturic acid (MHBMA) and 1,2-dihydroxybutyl mercapturic acid (DHBMA). Exposure differed between groups (p<0.05) with median values of 2.38, 1.62 and 0.88 microg/m(3) for toll collectors, the urban-weekday group and the suburban-weekend group, respectively. A refined ID-LC-MS/MS method enabled detection of MHBMA, previously detected only in occupational settings, with high frequency. MHBMA and DHBMA were detected in 95 and 100% of urine samples at levels (mean+/-S.D.) of 9.7+/-9.5, 6.0+/-4.3 and 6.8+/-2.6 ng/mL for MHBMA and 378+/-196, 258+/-133 and 306+/-242 ng/mL for DHBMA for the three different groups, respectively. Mean biomarker levels were higher among the toll collectors compared to the other two groups, however, the differences were not statistically significant (p>0.05). This study is the first to evaluate 1,3-butadiene biomarkers for subtle differences in environmental exposures. However, additional research will be required to ascertain whether the lack of statistical association observed here is real or attributable to unexpectedly small differences in exposure between groups (<1 microg/m(3)), non-specificity of the biomarker at low exposure, and/or small sample size.

Air Pollutants, Occupational↗
PubMed2005

Hemoglobin adducts and micronuclei in rodents after treatment with isoprene monoxide or butadiene monoxide.

1,3-Butadiene and isoprene (2-methyl-1,3-butadiene) are chemically related substances that are carcinogenic to rodents. The overall aim of this work is to elucidate the role of the genotoxic action of diepoxide metabolites in the carcinogenesis of the dialkenes. In vivo doses of the diepoxide metabolites were measured through reaction products with hemoglobin (Hb adducts) in studies of induced micronuclei (MN) in rodents. In the reaction with N-terminal valine in Hb, diepoxybutane and isoprenediepoxide form ring-closed adducts, pyrrolidines [N,N-(2,3-dihydroxy-1,4-butadiyl)valine and N,N-(2,3-dihydroxy-2-methyl-1,4-butadiyl)valine, respectively]. The method applied for Hb-adduct measurement is based on tryptic degradation of the protein and liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) analysis. Mice were given single i.p. injections of the monoepoxides of butadiene and isoprene, 1,2-epoxy-3-butene or 1,2-epoxy-2-methyl-3-butene, respectively. Rats were treated in the same way with 1,2-epoxy-3-butene. In mice pyrrolidine adduct levels increased with increasing administered doses of the monoepoxides. The in vivo dose of diepoxybutane was on average twice as high (0.29+/-0.059 mMh) as the in vivo dose of isoprenediepoxide (0.15+/-0.053 mMh) per administered dose (mmol/kg body weight) of the monoepoxides. In mice the genotoxic effects of the two monoepoxides, measured as the increase in the frequencies of micronuclei (MN), were approximately linearly correlated to the in vivo doses of the diepoxides (except at the highest dose of diepoxybutane). In rats the pyrrolidine-adduct levels from diepoxybutane were below the limit of quantification at all administered doses of 1,2-epoxy-3-butene and no significant increase was observed in the frequency of MN. Measurement of the ring-closed adducts to N-termini in Hb by the applied method permits analysis of in vivo doses of diepoxybutane and isoprenediepoxide, which may be further used for the elucidation of the mechanisms of carcinogenesis of butadiene and isoprene.

Animals↗
PubMed2001

A review of the epidemiology of 1,3-butadiene and chloroprene.

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.

Butadienes↗
PubMed2001

Butadiene--progress under the European Union Existing Substances Regulation.

A draft risk assessment report (RAR) for 1,3-butadiene has been produced by the UK under the European Union's Existing Substances Regulation (ESR). In line with the requirements of ESR, the RAR presents an evaluation of the hazards and risks of butadiene to human health (for workers, consumers and the general public) and to the environment. If as a result of the risk assessment, concerns for human health and/or the environment are identified, proposals for measures to reduce those risks may be developed. In relation to the human health elements of the ESR RAR for butadiene, the risk assessment involves a comparison of health effects against exposures in the three population sectors. The position arrived at on risk is described in qualitative rather than quantitative terms. For butadiene, the conclusion reached for the human health hazard assessment has been influenced significantly by both the animal and human data available. Species differences in toxicity, in particular with regard to mutagenicity and carcinogenicity, are considered along with the mechanistic arguments for these differences and their relevance for human health. The information presented in the RAR has been extensively discussed within the EU and a generally agreed position has been reached, with respect to human health hazard and risk. It is concluded that whilst the risks to human health at current exposure levels in the workplace, for consumers and following exposure via the environment are uncertain, there are concerns for human health effects for all three populations. Thus, there is a need to limit the risks. The next stage in the ESR process will be to consider what, if any, additional risk reduction measures may be required, taking into account existing control measures.

Butadienes↗
PubMed2001

Future research needs for the health assessment of 1,3-butadiene.

In recent years, several organizations have evaluated the health effects of 1,3-butadiene. Dissimilar conclusions about the carcinogenicity of 1,3-butadiene have been reached, due to differences in interpretation of the same data. Although 1,3-butadiene has been extensively studied, various uncertainties and data gaps remain which will require further clarification to reduce the uncertainties in future health assessments. This paper discusses future research needs respective of cancer and non-cancer effects that would be useful for future assessments as to how 1,3-butadiene affects health.

Air Pollutants↗
PubMed2001

A cohort mortality study among workers at a 1,3 butadiene facility.

This is a cohort mortality study of 2800 male workers employed at least 6 months between 1943 and 1996 at a 1,3-butadiene monomer production facility. Earlier analyses of mortality for this cohort found statistically significant deficits for the 'all causes of death' category, and a lower than expected mortality for most leading causes of death. Past analyses also showed a significant elevation for deaths from cancers of the lymphohematopoietic system that was mainly due to an increase in deaths from lymphosarcoma. The purpose of this update was to examine the patterns of mortality through the end of 1999, for five additional years of follow-up. Persons who had become eligible between the last cohort update and April 1996 were added. Cohort membership was closed after April 1996 due to the sale of the facility. A total of 1422 deaths through December 1999 were identified, giving over 200 more deaths than in the last report on this aging cohort. The standardized mortality ratio (SMR) for all causes of death was 89 [95% confidence interval (95% CI) =84-94], which is statistically significantly low, and that for all malignant neoplasms was 90 (95% CI=81-101). The SMR for all lymphohematopoietic cancers (LHC) was 141 (95% CI=105-186) and is statistically significant. The SMR for leukemia was 129 (95% CI=77-204) and for non-Hodgkin's lymphoma (NHL), 148 (95% CI=89-231). The LHC elevations again were found only in workers first employed before 1950 and, in the group with the highest potential for exposure to butadiene, the elevations were highest in the short-term workers. Survival analyses were performed for all LHC [International Classification of Diseases (ICD) codes 200-209], NHL (ICD codes 200, 202), and leukemia (ICD codes 204-207) using an estimate of cumulative butadiene exposure as a time-dependent explanatory variable defined as a combination of job exposure class, calendar time, and length of time in job. The relative risks for the above causes of death were essentially 1.0, suggesting that there was no increase in risk with increasing butadiene exposure.

Butadienes↗
PubMed1998

Evaluation and characterization of micronuclei in early spermatids of mice exposed to 1,3-butadiene.

The frequency of micronuclei induced in mouse meiotic cells after exposure to 1,3-butadiene has been evaluated in early spermatids. Germ cells were isolated from mice exposed to three butadiene concentrations (130, 250 and 500 ppm), at time intervals allowing to evaluate effects induced in late spermatocytes or at the stage of prelepotene/differentiating spermatogonia. The characterization of the origin of micronuclei, by simultaneous detection of centromeric and telomeric sequences, was also done on spermatid preparations from the 250 ppm concentration. The same analysis was carried out on a group of mice treated with the major butadiene metabolite, 1,2,3,4-diepoxybutane. The results obtained indicate a weak clastogenic effect of butadiene to premeiotic germ cells in the mouse.

Animals↗
PubMed1998

A comparison of male-mediated effects in rats and mice exposed to 1,3-butadiene.

There is current concern that exposure of men to certain agents such as radiation and smoking can adversely affect their offspring in terms of cancer outcome. Studies in laboratory animals after radiation have supported such an association, and other studies after male exposure to radiation and various chemicals have also resulted in congenital malformations. The present study was undertaken to examine congenital malformations in offspring from males exposed to 1,3-butadiene over a lower dose range than that in an earlier mouse study and to determine if there was a species difference in sensitivity between rats and mice. An earlier extended dominant lethal study of male CD-1 mice exposed by inhalation to 12.5 ppm and 1250 ppm of 1,3-butadiene for 6 h/day, 5 days/wk, for 10 weeks produced an increase in F1 abnormalities and late deaths at 12.5 ppm and in early deaths at 1250 ppm. The present study examined the same reproductive effects after exposure of male CD-1 mice for 6 h/day, 5 days/wk, for 4 weeks to 12.5, 65 and 130 ppm of 1,3-butadiene. There was no increase in early deaths at 12.5 ppm as in the earlier study but there were statistically significant increases in early deaths at 65 and 130 ppm study and these were not dose-related. There was a non-significant increase in F1 gross abnormalities at 130 ppm and no increase in late deaths. The present study also examined male Sprague-Dawley rats after exposure to 65,400 and 1250 ppm for 6 h/day, 5 days/wk, for 10 weeks. There were no effects on early deaths, late deaths, or congenital malformations in the rat study. There was a reduction in implants at 65 ppm but this was not considered to be biologically/genetically significant as there was no corresponding increase in early deaths and the response was not dose-related. The differences observed between the rat and mouse studies would confirm the greater sensitivity to 1,3-butadiene of the mouse by comparison with the rat as reported by other workers for other parameters.

Animals↗
PubMed1993

Chemical suppression of a subpopulation of primitive hematopoietic progenitor cells: 1,3-butadiene produces a hematopoietic defect similar to steel or white spotted mutations in mice.

Chronic exposure of mice to 1,3-butadiene produces a macrocytic-megaloblastic anemia, thymic hypoplasia, and an increased incidence of T-cell lymphoma/leukemia. This is reminiscent of pathologies observed in mice bearing mutations at the W and Sl loci, which are deficient in c-kit and c-kit ligand (CKL), respectively. The influence of 3,4-epoxybutene (EB), the primary metabolite of 1,3-butadiene, on the colony-forming response of hematopoietic progenitor cells (HPCs) from C57BL/6, Sl, and W mice was investigated in order to elucidate the role of altered HPC regulation in the pathogenesis of 1,3-butadiene toxicity. EB pretreatment suppressed interleukin 3 colony formation and abrogated CKL synergism of the granulocyte-macrophage/colony-stimulating factor (GM-CSF) response in C57BL/6 cells, had no effect on colony formation induced by GM-CSF or granulocyte/colony-stimulating factor (G-CSF) alone, and failed to suppress CKL-induced synergism of the G-CSF response. Experiments conducted with cells from Sl and W mice revealed that they lack the same primitive HPC targeted by EB. EB pretreatment in vitro and butadiene exposure in vivo mimic hematopoietic defects seen in W and Sl mice, suggesting that the pleotypic pathologies encountered in these murine models may be largely due to a common defect in primitive HPCs. Susceptibility to EB appears to define a functional subpopulation of primitive HPCs and illustrates that differences observed in the susceptibility of specific cytokine responses to chemical/drug exposure may provide a valuable tool for characterizing functional subpopulations of HPCs.

Animals↗
PubMed1979

Inhalation toxicity studies with 1,3-butadiene -- 2. 3 month toxicity study in rats.

The available toxicological data for 1,3-butadiene are limited and contradictory. Three month toxicity and two year carcinogenicity studies have therefore been initiated to identify any potential hazard to occupationally exposed personnel. The results of the 3 month study are reported in this paper. Five groups of Sprague-Dawley rats were exposed to 1,3-butadiene gas at atmospheric concentrations of 0, 1000, 2000, 4000 and 8000 ppm v/v respectively, 6 hours/day, 5 days/week for 13 weeks. Forty male and forty female animals were used in each group, of which 10 of each sex were killed at 2 and 6 weeks. Exposure took place in 5 chambers, in an area prepared specifically for the handling of a potentially explosive gas-air mixture at concentrations just below the lower explosive limit. No untoward effects attributable to exposure were observed, except a moderately increased salivation, particularly in female animals during the last 5--8 weeks of exposure, at higher concentrations of butadiene. No effects considered to be attributable to treatment were seen in growth rate, food consumption, hematological and blood biochemical investigations or urine analysis after 2, 6 and 13 weeks exposure. Macroscopic and histopathological examination after 2, 6 and 13 weeks exposure showed no untoward changes related to exposure to butadiene gas. Erythrocyte and brain cholinesterase, erythrocyte osmotic fragility and neutrophil phagocytosis were also unaffected by treatment.

Air Pollutants↗
PubMed1990

Analysis of 1,3-butadiene and other selected gas-phase components in cigarette mainstream and sidestream smoke by gas chromatography-mass selective detection.

An analytical procedure was developed for the analysis of 1,3-butadiene, acrolein, isoprene, benzene and toluene in the gas phase of cigarette smoke and environmental tobacco smoke (ETS) utilizing cryogenic gas chromatography-mass selective detection (GC-MSD). The MSD was operated in the selective ion monitoring (SIM) mode. The compounds of interest eluted in less than 15 min. The gas phase of freshly generated mainstream smoke was introduced into the GC-MSD via a 10-port gas sampling valve on a puff-by-puff basis. This method minimizes the ageing of tobacco smoke. The levels of 1,3-butadiene in the mainstream smoke ranged from 16 to 75 micrograms/cigarette. The gas phase of sidestream smoke was trapped in methanol using three midget impingers at -78 degrees C. The amount of 1,3-butadiene in the sidestream smoke ranged from 205-361 micrograms/cigarette. The concentration of 1,3-butadiene in ETS in a smoke-filled bar amounted to 2.7-4.5 micrograms/m3.

Acrolein↗
PubMed1994

Activation of H-ras is prevalent in 1,3-butadiene-induced and spontaneously occurring murine Harderian gland tumors.

Treatment of B6C3F1 mice with concentrations of 62.5-625 p.p.m. 1,3-butadiene by inhalation for up to 2 years causes a significantly increased incidence of Harderian gland (HG) neoplasms over untreated controls (Melnick,R., Huff,J., Chou,B.J. and Miller,R.A. Cancer Res., 50, 6592-6599, 1990). Since a specific K-ras mutation (codon 13 GGC-->CGC) had previously been described in lung and liver tumors from 1,3-butadiene-treated B6C3F1 mice, we analyzed 23 adenomas and six adenocarcinomas of the HG from mice exposed to 1,3-butadiene for this mutation and mutations in the H-ras gene. We also examined ras activation in 16 spontaneously occurring HG adenomas and one adenocarcinoma. DNA samples were prepared from paraffin-embedded tissues and analyzed by PCR followed by direct sequencing methods. Only one 1,3-butadiene-induced HG tumor contained the K-ras codon 13 mutation previously detected in lung and liver tumors. However, 16/29 HG tumors from the treated B6C3F1 mice contained H-ras codon 61 mutations. The mutations detected were: 12 CAA-->CGA transitions, two CAA-->CTA and two CAA-->AAA transversions. Eleven of 17 spontaneous HG tumors contained mutations in H-ras codon 61: five CAA-->CGA transitions, two CAA-->CTA transversions and four CAA-->AAA transversions. While the spectrum of ras mutations did not differ between the spontaneously occurring and chemically induced tumors, these data indicate that activation of H-ras contributes to the process of HG tumorigenesis in both groups of these neoplasms.

Animals↗
PubMed1997

32P-postlabelling/HPLC assay reveals an enantioselective adduct formation in N7 guanine residues in vivo after 1,3-butadiene inhalation exposure.

We have established a protocol that allows qualitative and quantitative determination of butadiene monoepoxide-DNA adducts formed as a result of inhalation exposure to 1,3-butadiene. We observed that in this particular case in vivo samples required extensive sample purification to facilitate a low background. Sample preparation included a solid phase extraction carried out with a strong anion exchange column and one-dimensional ion exchange TLC. The ultimate analysis is based on reverse phase HPLC with on-line radioactivity and UV detectors. The qualitative identification and quantitation is based on characterized markers, which are used as external and internal standards. Modified 3'-dGMP markers were used to control labelling efficiency, which varies, and modified 5'-dGMP markers were used as an optical standard to qualitatively assign the products and to determine recovery of the sample preparation. Using this method we were able to demonstrate, for the first time, specific enantio- and regioisomeric adduct formation at the N7 position of guanine residues in liver DNA of rats inhalation-exposed to 1,3-butadiene. The major adduct formed was the C-2 isomer derived from the R enantiomer of butadiene monoepoxide, contributing 47% of all adducts formed at the N7 position of guanine. The relative proportions of the remaining three other adducts detected were 22 (R C-1), 18 (S C-2) and 14% (S C-1) respectively. Inhalation exposure to 200 p.p.m. for 5 days resulted in an alkylation level of 7.2 fmol/10 microg DNA or 2.4 adducts/10(-7) normal nucleotides.

Administration, Inhalation↗