Clinical and experimental research into the pathogenesis of toxic effect of styrene. VI. The effect of styrene on carbohydrate balance, experimental research.
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Animals↗
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Clinical and experimental research into the pathogenesis of toxic effect of styrene. VII. Appraisal of the nervous system in the workers exposed to styrene.
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Adolescent↗
Emulsion intercalation of smectite clays with comb-branched copolymers consisting of multiple quaternary amine salts and a poly(styrene-butadiene-styrene) backbone.
Layered silicates were intercalated with comb-branched copolymers consisting of a hydrophobic polystyrene-b-poly(ethylene/butylene)-b-polystyrene (SEBS) backbone and multiple pendants of poly(oxyalkylene) (POA) quaternary ammonium salts. The requisite intercalating agents were synthesized by grafting POA amines on the maleated SEBS. The corresponding SEBS-POA amine salts were found to have two functions, the capability to emulsify toluene/water mixtures to fine particle sizes of 60-70 nm in diameter and to exchange ions with sodium montmorillonite. The resulting silicate hybrids were characterized by X-ray diffraction and transmission electron microscopy. Two types of intercalations with silicate d spacing of 18 and 50 A were obtained, in which the dissimilarity is attributed to disparate polymer incorporations, POA pendants only or the combination of both the SEBS backbone and POA in the gallery. Furthermore, the two conformations of polymer-intercalated silicates are reversibly transformable by varying emulsion conditions, micelle sizes, and solvents.
Journal Article↗
Acrylonitrile, acrylic and modacrylic fibres, and acrylonitrile-butadiene-styrene and styrene-acrylonitrile copolymers.
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Abnormalities, Drug-Induced↗
[Hygienic chemical studies on plastics (V). Migration of acrylonitrile from acrylonitrile-butadiene-styrene copolymer and acrylonitrile-styrene copolymer into various food simulating solvents in long period (author's transl)].
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Acrylonitrile↗
Biological monitoring of exposure to low concentrations of styrene.
A field study was conducted on 39 male workers exposed to styrene at concentrations below 40 ppm (time weighted average, TWA). Analyses were carried out on environmental air, exhaled air, blood, urine, and two major urinary metabolites of styrene: mandelic acid (MA) and phenylglycoxylic acid (PGA). Head space gas chromatography (GC) with a flame ionization detector (FID) was used for determination of styrene in blood and urine. Postexposure exhaled air was analyzed using capillary GC. Environmental styrene exposure was measured by personal sampling using carbon cloth personal samplers. Urinary metabolites of styrene were determined by high pressure liquid chromatograph (HPLC). When the end-of-shift breath, blood, and urine styrene levels were compared with environmental TWA values, blood styrene correlated best with styrene in air (r = 0.87), followed by breath styrene (r = 0.76). Poor correlation (r = 0.24) was observed between environmental styrene exposure and urine styrene. When styrene metabolites were compared with environmental styrene, the sum of urinary MA and PGA correlated better with styrene in air than MA or PGA alone. The correlations between urinary metabolites and environmental styrene improved when corrected for the specific gravity of urine. Even better correlations were observed when the urinary metabolites were corrected for creatinine. The correlation coefficients for environmental styrene and end-of-shift MA, PGA, and MA+PGA were 0.83, 0.84, and 0.86, respectively. The correlation coefficients between environmental styrene and next morning urinary metabolites fell to 0.47, 0.61, and 0.65 for MA, PGA, and MA+PGA, respectively. These results suggest that determination of the total MA and PGA in urine samples is preferred than separate measurements of MA or PGA. The good correlation between environmental exposure and styrene in the exhaled air also suggests that breath styrene level can be a useful indicator for low level styrene exposure, as the method is specific, noninvasive, and rapid. Urinary styrene seems to be a less reliable indicator for low level styrene exposure.
Adult↗
Review of the metabolic fate of styrene.
Styrene and styrene oxide have been implicated as reproductive toxicants, neurotoxicants, or carcinogens in vivo or in vitro. The use of these chemicals in the manufacture of plastics and polymers and in the boat-building industry has raised concerns related to the risk associated with human exposure. This review describes the literature to date on the metabolic fate of styrene and styrene oxide in laboratory animals and in humans. Many studies have been conducted to assess the metabolic fate of styrene in rats, and investigations on the metabolism of styrene in humans have been of considerable interest. Limited research has been done to assess metabolism in the mouse. The metabolism of styrene to styrene oxide and further conversion to styrene glycol (via epoxide hydrolase), mandelic acid, and phenylglyoxylic acid has been given considerable attention, and is considered to be the major pathway of activation and detoxication for humans. While the hydrolysis of styrene oxide to styrene glycol historically has been the favored pathway for the rat, studies in more recent years have indicated that glutathione conjugation also is a viable and significant pathway for both the rat and the mouse. This pathway has not been established in humans. Mandelic acid and phenylglyoxylic acid have been used as urinary markers of exposure in humans exposed to styrene. Extensive investigations have been conducted on the kinetics of styrene and styrene oxide in rodents. In people, the kinetics of styrene and styrene oxide in the blood of occupationally exposed workers and volunteers have been determined. Pharmacokinetic models developed in the last decade have become increasingly complex, with the most recent physiologically based model describing the kinetics of styrene and styrene oxide. This model shows pronounced species differences in sensitivity coefficients for styrene or styrene oxide between mice, rats, and humans, where mice are the more sensitive species to the Vmax for both epoxide hydrolase and monooxygenase. This result is particularly interesting in light of the recent findings of extensive mortality and hepatotoxicity for mice exposed to relatively low levels of styrene (250 to 500 ppm), while rats and humans exhibit only nasal and eye irritations at exposure concentrations well above 500 ppm.
Animals↗
A re-evaluation of the cytogenetic effects of styrene.
Results from new chromosome studies in laboratory animals, comparative investigations of styrene metabolism and pharmacokinetics in humans and animals, and several recent cytogenetic surveys of styrene-exposed workers have necessitated a comprehensive re-evaluation of the chromosome-damaging effects of this chemical. Both styrene and its genotoxic metabolite, styrene oxide, can induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in vitro, but the chromosome-damaging ability of styrene is only manifested if test conditions favour its metabolic activation over inactivation. There is no convincing evidence of styrene clastogenicity in experimental animals. Styrene oxide is clastogenic only at lethal concentrations via i.p. injection in Chinese hamsters (but not via inhalation) or after oral treatment of mice, a route considered inappropriate for investigating the chromosome-damaging potential of inhaled styrene in man. Styrene and styrene oxide can induce SCE in animals at very high concentrations. Eighteen of 52 cytogenetic studies (CA, micronuclei, SCE) on peripheral blood lymphocytes of styrene workers have reported increases in chromosome damage. The positive findings are not compatible with the conclusion that styrene is responsible for the cytogenetic effects for the following reasons. (a) The positive or negative outcome of the various investigations bears no relationship to the degree of exposure of the workers. (b) There is no convincing evidence of a positive dose response relationship. (c) The relative induction of CA and SCE in worker studies are the opposite of observations of styrene effects in cultured lymphocytes and in laboratory animals. (d) The reports of chromosome-type exchanges in some studies of styrene workers is inconsistent with observations of styrene clastogenicity in cultured lymphocytes. (e) Reports of SCE induction in workers exposed to low concentrations of styrene are not compatible with results of animal inhalation studies, particularly in view of the differences in styrene metabolism and pharmacokinetics between humans and rodents. The increases in cytogenetic effects reported in some studies on styrene workers are probably attributable to the presence of other chromosome-damaging agents in the workplace and/or to inadequate investigations.
Animals↗
Investigation of bioactivation and toxicity of styrene in CYP2E1 transgenic cells.
Styrene has been found to be toxic to the respiratory system, and the toxicity of styrene is metabolism-dependent. CYP2E1 is suggested to be one of the cytochrome P450 enzymes responsible for the bioactivation of styrene. Our work focused on the roles of CYP2E1 and epoxide, a metabolite of styrene epoxidation, in the cytotoxicity of styrene. Styrene was found to be more toxic to h2E1 cells than to the wild type, while there was no difference found when styrene oxide was administered. Both soluble and microsomal epoxide hydrolase inhibitors dramatically enhanced styrene toxicity. Glutathione and glutathione ethyl ester showed protection against styrene cytotoxicity. Cytotoxicity of a selection of styrene analogues, such as ethylbenzene, vinylcyclohexane, and ethylcyclohexane, was assessed to determine if unsaturation is required for styrene toxicity. Ethylbenzene and vinylcyclohexane were found to be as toxic as styrene to h2E1 cells, whereas little toxicity of ethylcyclohexane to h2E1 cells was observed. This indicates the importance of vinyl group of styrene in its cytotoxicity, but saturation of the vinyl group does not necessarily eliminate styrene toxicity. An N-acetylcysteine conjugate derived from styrene oxide was identified by LC/MS/MS in the sample obtained from the incubation of h2E1 cell lysate with styrene in the presence of N-acetylcysteine. Formation of the N-acetylcysteine conjugate was found to be NADPH-dependent. These studies provided strong evidence in support of toxic role of styrene epoxide metabolite in styrene toxicity.
Acetylcysteine↗
NTP-CERHR monograph on the potential human reproductive and developmental effects of styrene.
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for styrene to cause adverse effects on reproduction and development in humans. Styrene was selected for evaluation because of (1) public concern about styrene exposure and (2) recently available exposure studies. Styrene (ethenylbenzene; CAS RN: 100-42-5) is a high production volume chemical (a million pounds or more produced each year) and is used in the production of polystyrene resins and as a co-polymer with acrylonitrile and 1,3-butadiene. Styrene is found in items such as foam cups, dental fillings, matrices for ion exchange filters, construction materials, and boats. It is also used in protective coatings, reinforced glass fiber, agricultural products, and as a food additive. The Food and Drug Administration regulates styrene for use as a synthetic flavoring substance and as a component of polymers in contact with dry food, and also regulates the amount of residual styrene monomer allowed in polystyrene intended for use in contact with food. The public can be exposed to styrene by ingesting food or drink that has been in contact with styrene polymers or through inhalation of polluted air and cigarette smoke. The results of this evaluation on styrene are published in a NTP-CERHR monograph that includes: (1) the NTP Brief, (2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Styrene, and (3) public comments received on the expert panel report. The NTP reached its conclusion of negligible concern for adverse developmental and reproductive effects resulting from styrene exposures in humans based on information presented in the NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Styrene and the public comments on that report. This conclusion is based on estimated exposures in both the general population and in people whose occupation involves styrene exposure. The expert panel estimated styrene exposure in the general U.S. population to be less than 0.3 microg/kg body weight/day in nonsmokers and 3.51 and 2.86 microg/kg body weight/day in smokers ages 12-19 years and 20-70 years, respectively. Average occupational exposures are estimated to range from 1,400-52,000 microg/kg body weight/day. Studies in humans show no evidence that occupational exposures or exposure of the general population to styrene adversely affect reproduction or development. Further, data from experimental animal studies show no adverse reproductive or developmental effects at styrene doses far above human exposure levels. The NTP will transmit the NTP-CERHR monograph on styrene to federal and state agencies, interested parties, and the public and it will be available in electronic PDF format on the CERHR web site http://cerhr.niehs.nih.gov and in printed text or CD-ROM from the CERHR: M.D. Shelby, Ph.D., Director, CERHR, NIEHS, P.O. Box 12233, MD EC-32, Research Triangle Park, NC 27709, 919-541-3455 [phone], 919-316-4511 [fax], shelby@niehs.nih.gov [email].
Animals↗
Metabolic interactions of 1,3-butadiene and styrene in male B6C3F1 mice.
Butadiene and styrene are a mixture of hazardous air pollutants found in the workplace of industries producing polymers such as styrene-butadiene rubber. Both butadiene and styrene require metabolic activation to exert their genotoxic effect; therefore metabolic interactions may influence their genotoxicity. Our objective was to quantitate potential metabolic interactions in mice exposed to a mixture of butadiene and styrene. The rate of metabolism of butadiene and styrene was estimated from the steady-state rate of uptake of the chemicals by male B6C3F1 mice exposed for 8 hr in a dynamic, whole-body inhalation system to 100 or 1000 ppm butadiene in combination with 0, 50, 100, or 250 ppm styrene. Styrene, styrene oxide, 1,2-epoxy-3-butene, and 1,2:3,4-diepoxybutane concentrations in blood were measured by gas chromatography-mass spectrometry at 2, 4, 6, and 8 hr of exposure. As the styrene concentration in the mixture increased, the rate of butadiene metabolism was inhibited up to 48%. 1,2-Epoxy-3-butene blood concentrations were increased by approximately 1.5-fold; however, 1,2:3,4-diepoxybutane blood concentrations were unaffected. Styrene uptake in the inhalation system was inhibited slightly by exposure with butadiene, but styrene blood concentrations increased significantly as the butadiene concentration in the mixture increased to 1000 ppm. Blood concentrations of styrene oxide increased approximately 1.6-fold for the 250-ppm styrene exposures when the butadiene concentration was increased from 0 to 1000 ppm. The data suggest that metabolic interactions occurred among the reactive metabolites (e.g., competition for detoxication pathways) as well as between butadiene and styrene in mice exposed to mixtures of butadiene and styrene. However, metabolic interactions were significant only at concentrations of butadiene and styrene higher than those typically observed in the workplace of industries producing polymers of butadiene and styrene.
Animals↗
Possible regulatory role for nonaromatic carbon sources in styrene degradation by Pseudomonas putida CA-3.
Styrene metabolism in styrene-degrading Pseudomonas putida CA-3 cells has been shown to proceed via styrene oxide, phenylacetaldehyde, and phenylacetic acid. The initial step in styrene degradation by strain CA-3 is oxygen-dependent epoxidation of styrene to styrene oxide, which is subsequently isomerized to phenylacetaldehyde. Phenylacetaldehyde is then oxidized to phenylacetic acid. Styrene, styrene oxide, and phenylacetaldehyde induce the enzymes involved in the degradation of styrene to phenylacetic acid by P. putida CA-3. Phenylacetic acid-induced cells do not oxidize styrene or styrene oxide. Thus, styrene degradation by P. putida CA-3 can be subdivided further into an upper pathway which consists of styrene, styrene oxide, and phenylacetaldehyde and a lower pathway which begins with phenylacetic acid. Studies of the repression of styrene degradation by P. putida CA-3 show that glucose has no effect on the activity of styrene-degrading enzymes. However, both glutamate and citrate repress styrene degradation and phenylacetic acid degradation, showing a common control mechanism on upper pathway and lower pathway intermediates.
Aldehyde Oxidoreductases↗
Temporal association between serum prolactin concentration and exposure to styrene.
BACKGROUND: Previous studies have suggested that occupational exposure to styrene is associated with increased serum levels of the anterior pituitary hormone prolactin (PRL). AIMS: To test the hypotheses that: (1) the effect of styrene exposure on PRL secretion is an acute effect, not a subchronic or chronic effect; (2) blood styrene, as a measure of absorbed dose, is a stronger predictor of serum PRL level than personal breathing zone air styrene concentration. METHODS: Subjects were recruited from 17 workplaces in the reinforced plastics industry. Personal breathing zone air styrene, whole blood styrene, and serum PRL were measured during one to three sessions, approximately one year apart. Linear multiple regression was used to model the relations between acute (air styrene or blood styrene obtained at same time as PRL), subchronic (average air or blood styrene over two or three sessions), and chronic (years of work in industry or facility times average air styrene over all sessions) indices of styrene exposure and serum PRL. RESULTS: Acute blood styrene concentration was the strongest predictor of serum PRL concentration, with the model predicting a 2.06-fold increase in PRL (95% CI 1.11 to 3.84) for every 10-fold increase in blood styrene. Serum PRL tended to increase with increasing styrene exposure in both men and women; however, women tended to have higher PRL levels. For women, the change in blood styrene between sessions 1 and 2 was a significant predictor of the change in serum PRL between sessions. CONCLUSIONS: Results confirm that styrene exposure enhances serum PRL concentrations and support an acute effect of styrene on PRL secretion.
Adolescent↗
Metabolism and genotoxicity of styrene.
An overview on the metabolism and genotoxicity of styrene is given in this article. The mutagenic potency of styrene has been confirmed in a number of test systems providing the metabolic activation of styrene. Styrene is converted to styrene-7,8-oxide as catalyzed by cytochrome P-450 cored enzyme complex. Styrene-7,8-oxide is mutagenic in prokaryotic and eukaryotic test systems without metabolic activation. It reacts with nucleic acid bases, especially with deoxyguanosine producing 7-alkylguanine and deoxycytidine producing N-3 alkylcytosine. Quite recently, styrene-7,8-oxide has been found to be a potent carcinogen in rats. In human whole blood cultures, styrene is metabolized into styrene-7,8-oxide. Styrene is able to induce both SCEs and chromosomal aberrations in cultured lymphocytes. The clastogenic action of styrene can be explained by the metabolism of styrene into styrene-7,8-oxide in cultured human blood cells. Although also an arene oxide, styrene-3,4-oxide, has been suggested in the biotransformation of styrene, the evidence so far supports the view that the vinyl group oxidation and oxirane formation plays a predominant role in the genotoxicity of styrene.
Animals↗
Effects of simultaneous administration of ethanol on styrene metabolism under fed and fasted conditions in the perfused rat liver.
The purpose of this study was to clarify the simultaneous administration of ethanol on styrene metabolism in the perfused rat liver under fed and fasted conditions. Styrene uptake rate, production rate of styrene glycol, oxygen consumption rate, and changes in reduced pyridine nucleotide fluorescence were monitored in the perfused rat liver. The effects of ethanol on parameters of styrene metabolism were observed in rat livers under fed and fasted conditions: fed (group I), fasted (group II), and fasted with xylitol in the perfusate (group III). The simultaneous administration of ethanol and styrene significantly decreased styrene uptake rate, production rate of styrene glycol, and oxygen consumption rate, and produced significant reduction of pyridine nucleotide fluorescence as compared with the single administration of styrene in groups I and III. In contrast, the simultaneous administration of ethanol and styrene significantly increased the production of styrene glycol and oxygen consumption as compared with the single administration of styrene in group II. Significant effects on the styrene uptake rate and the reduced pyridine nucleotide fluorescence were observed with regard to factors of both nutritional status and the interaction between ethanol and nutritional status by two-way analysis of variance. These findings showed that the effects of ethanol on styrene metabolism in the liver were dependent upon the nutritional status of the animal. The fed and fasted conditions affected the effect of ethanol on styrene metabolism by changing the supply of NADPH to the mixed-function oxidase system. In conclusion, ethanol suppressed styrene metabolism in the fed condition, but enhanced it in the fasted condition. This phenomenon should be considered in the prevention of occupational hazard of styrene exposure in industrial workers with alcohol drinking habits and nutritional problems.
Animals↗
Genotoxicity and cytotoxicity in male B6C3F1 mice following exposure to mixtures of 1,3-butadiene and styrene.
1,3-Butadiene and styrene are oxidized, in part, by cytochrome P450 2E1 and have been shown to metabolically interact in rodents exposed by inhalation to mixtures of both compounds. Because the reactive metabolites of butadiene and styrene are thought to be responsible for the toxicity of each compound, metabolic interactions may alter the response in animals exposed to mixtures of butadiene and styrene compared with the response in animals exposed to butadiene alone or styrene alone. The purpose of this study was to quantitate alterations in genotoxicity and cytotoxicity in male B6C3F1 mice exposed to mixtures of butadiene and styrene. Male B6C3F1 mice were exposed to 6.25, 62.5, 200, or 625 ppm butadiene alone, 50 ppm styrene alone, or mixtures of 6.25, 62.5, 200, or 625 ppm butadiene and 50 ppm styrene. Genotoxicity was assessed by quantitating the frequency of micronucleated polychromatic erythrocytes in bone marrow. Cytotoxicity was assessed by counting total spleen and thymus cells and by quantitating the frequency of polychromatic erythrocytes in the peripheral blood. Butadiene and mixtures of butadiene and styrene were genotoxic in mice, as shown by a significant increase in the frequency of micronucleated polychromatic erythrocytes. The increased frequency following exposure to mixtures of butadiene and styrene was not significantly different compared with the frequency following exposure to butadiene alone. Styrene and mixtures of butadiene and styrene were cytotoxic in mice, as shown by significantly decreased number of spleen cells. Exposure to mixtures of butadiene and styrene with butadiene concentrations of 62.5 or 625 ppm significantly reduced the number of thymus cells. Exposure to 200 ppm or 625 ppm butadiene alone, or to mixtures of 200 ppm or 625 ppm butadiene and 50 ppm styrene, significantly reduced the frequency of polychromatic erythrocytes in the peripheral blood. The results of the study demonstrate that exposure to mixture of butadiene and styrene does not reduce the respective genotoxicity of butadiene or cytotoxicity of styrene.
Animals↗
Effects of intermittent styrene inhalation, ethanol intake and their combination on drug biotransformation in rat liver and kidneys.
The modifying effects of daily ethanol ingestion in the drinking water as a 15 % solution (v/v) on drug biotransformational changes induced by inhalation exposure to styrene (300 ppm or 1260 mg/m3, 6 h daily, 5 d/week, up to 17 weeks) were studied in rat liver and kidney. The drug hydroxylation activities (7-ethoxycoumarin O-deethylase and 2,5-diphenyloxazole hydroxylase) both in liver and in kidneys were increased more by ethanol ingestion than by styrene inhalation. When administered in combination, styrene and ethanol exerted mostly an additive enhancing effect. However, hepatic NADPH-cytochrome c reductase activity was reduced both in styrene and in ethanol-treated rats. Hepatic styrene oxide hydratase activity was virtually unaffected by styrene treatments. The depression of glutathione concentration in liver was greater after styrene-ethanol than after styrene treatment alone. The hepatic UDPglucuronosyltransferase activity was enhanced slightly both in styrene and in styrene-ethanol rats. The binding affinity of styrene towards cytochrome P-450 was increased after styrene inhalation as shown by lowered K8 values. The perirenal fat concentration of styrene showed a rough inverse relationship to the overall monooxygenation activities in liver and kidney. Despite the additively induced enzyme activities in styrene-ethanol-treated rats the accumulation of styrene in fat of these animals was on the whole somewhat greater, suggesting that these two solvents in vivo also have mutual inhibitory effects on biotransformation.
Animals↗
Species-specific pharmacokinetics of styrene in rat and mouse.
The pharmacokinetics of styrene were investigated in male Sprague-Dawley rats and male B6C3F1 mice using the closed chamber technique. Animals were exposed to styrene vapors of initial concentrations ranging from 550 to 5000 ppm, or received intraperitoneal (i.p.) doses of styrene from 20 to 340 mg/kg or oral (p.o.) doses of styrene in olive oil from 100 to 350 mg/kg. Concentration-time courses of styrene in the chamber atmosphere were monitored and analyzed by a pharmacokinetic two-compartment model. In both species, the rate of metabolism of inhaled styrene was concentration dependent. At steady state it increased linearly with exposure concentration up to about 300 ppm; more than 95% of inhaled styrene was metabolized and only small amounts were exhaled unchanged. At these low concentrations transport to the metabolizing enzymes and not their metabolic capacity was the rate limiting step for metabolism. Pharmacokinetic behaviour of styrene was strongly influenced by physiological parameters such as blood flow and especially the alveolar ventilation rate. At exposure concentrations of styrene above 300 ppm the rate of metabolism at steady state was progressively limited by biochemical parameters of the metabolizing enzymes. Saturation of metabolism (Vmax) was reached at atmospheric concentrations of about 700 ppm in rats and 800 ppm in mice, Vmax being 224 mumol/(h.kg) and 625 mumol/(h.kg), respectively. The atmospheric concentrations at Vmax/2 were 190 ppm in rats and 270 ppm in mice. Styrene accumulates preferentially in the fatty tissue as can be deduced from its partition coefficients in olive oil:air and water:air which have been determined in vitro at 37 degrees C to be 5600 and 15. In rats and mice exposed to styrene vapors below 300 ppm, there was little accumulation since the uptake was rate limiting. The bioaccumulation factor body:air at steady state (K'st*) was rather low in comparison to the thermodynamic partition coefficient body:air (Keq) which was determined to be 420. K'st* increased from 2.7 at 10 ppm to 13 at 310 ppm in the rat and from 5.9 at 20 ppm to 13 at 310 ppm in the mouse. Above 300 ppm, K'st* increased considerably with increasing concentration since metabolism became saturated in both species. At levels above 2000 ppm K'st* reached its maximum of 420 being equivalent to Keq. Pretreatment with diethyldithiocarbamate, administered intraperitoneally (200 mg/kg in rats, 400 mg/kg in mice) 15 min prior to exposure of styrene vapours, resulted in effective inhibition of styrene metabolism, indicating that most of the styrene is metabolized by cytochrome P450-dependent monooxygenases.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration, Inhalation↗