Styrene CAS No. 100-42-5

Synonyms. Cinnamene; Cinnamol; Ethylbenzene; Phenylethylene; Styrol; Styrolene; Vinyl benzene.

Properties. Colorless, viscous liquid with a characteristic penetrating unpleasant ()clear. On exposure to air or light undergoes polymerization and oxidation. Water solubility is I _2S mg/l at 20 (' and 320 tug/I at 25"C, soluble in alcohol. ()doe perception threshold is ().()5 to ().12 mg/l or 0.01 I mg/l;02,010 taste perception threshold is 0.06 mbl.¹

Applications and Exposure. S. is used as a monomer in the production of various plastics, resins and vulcanizes: styrenebutadiene rubber, acrylonitrile-butadiene-styrene (ABC) polymer, and styrene-acrylonitrile copolymer (SAN) resins. It is also used as a cross-linking agent and in solvent for unsaturated polyester resins. S. has been found in food packaged in polystyrene containers (in yogurt up to 0.02 mg/l),² and in water (0.05 to 0.1 mg/l).^3,4 It was shown to migrate From ABC-polymers into water: t).()5 mg/I for 24 h at 37°C.' Concentrations reported in drinking eater arc ().()1 to ().()s mg/l.

Acute Toxicity. In rats, LD₅₀ varies from 5 to 8 g/kg BW.⁵ Poisoned animals displayed NS impairment, convulsions, loss of reflexes, cyanosis, and body temperature drop. Oil administration of the lethal oral doses, rats became comatose and died. Gross pathological examination revealed hepatic dystrophic changes and, incidentally, renal changes,⁶ but also diffuse damage to the upper sections of the CNS. The maximum tolerated closes appear to be 0.5 mg/kg BW for mice and 2 g/kg BW for rats. These doses caused no appreciable morphological changes.¹

Repeated Exposure. Male rats were given 1 ml/kg BW by oral intubation for 15 d. There was an increase in the serotonin and noradrenaline contents in the brain, but no changes in the amount of dophamine were marked. The monoaminooxidase activity was suppressed, but that of ACE was unaltered.⁷ Doses of 100 and 200 mg/kg BW administered to rats over the same period of time caused no disruption of behavioral reactions. An increase was observed in the serotonin level in the hippocampus and hypothalamus as a result of exposure to the 20() mg/kg BW dose.⁷

Short-term Toxicity. Doses up to 500 mg/kg BW caused irritation of the esophagus and stomach and hyperkeratosis of the forestomach. No hematological changes were observed in the short-term oral studies in rats.⁶ The dose of 400 mg/kg BW given orally for 100 d produced elevated levels of hepatic AST and ALT. In addition, significantly decreased activity of hepatic acid phosphatase and of other enzymes was found. Histopathological examination revealed liver focal necrosis, which was supported by the biochemical analysis described earlier.⁸

Long-term Toxicity. In a 6-month oral toxicity study (Wolf et al., 1956), the NOEL of 133 mg/kg BW was suggested. In the more recently reported experiment, beagle dogs were given S. in a peanut oil suspension by gavage for up to 561 d.⁹ The NOAEL of 200 mg/kg BW was identified in this study. Parameters investigated in another oral rat study were clinical signs, mortality, growth, food and water intake, hemograms, clinical chemistry, urinalysis, gross necropsy, and histopathology. The NOAEL was found to he 125 mg/l of drinking water, that corresponds to 7.7 mg/kg BW for males and 12 mg/kg BW for females.¹⁰

Reproductive Toxicity. Embryotoxicity. Negative results were reported in gals following oral dosing with 90 to 150 mg/kg BW.⁸ No adverse effects were observed in Sprague-Dawley rats in the three generation reproductive study: there were no treatment-related changes in rats exposed for two years to 125 or 250 ppm in drinking water. ¹² Teratogenicity. The oral teratogenicity study in rats did not reveal maternal toxicity, teratogenic, or embryotoxic effect at dose-levels up to and including 300 mg/kg BW.¹³ Teratogenic effect for chicken embryos, rats. and rabbits. as well as fetotoxicity in mice and hamsters following inhalation was reported in some studies. ^{11, 13} Inhalation of S. at low concentrations affects the gonads, embryogeny, and the offspring of mammals. S. penetrates through the placenta into the milk of feeding females.¹⁴

Genotoxicity. S. requires metabolic activation to produce genotoxic action. Mutagenic effect is to the formation of styrene oxide (q.v.) in the body. S. is transformed into styrene oxide in the blood of humans under the action of oxyhemoglobin of erythrocytes. S. is mutagenic in a variety of test systems, results being sometimes rather equivocal. It induces gene mutations in prokaryotic anti eukaryotic microorganisms, in Dr. melanogaster, and in mammalian cells in vitro. Reports on chromosomal abnormalities are also contradictory. When positive results were observed. mainly high doses were used.¹⁵ According to Simula and Priestly,¹⁶ S. produced weak genotoxic response in the hone marrow micronucleus, sperm morphology, and SCE assays in Swiss mice and Porton rats

Carcinogenicity. Carcinogenicity studies in mice and rats with various routes of administration did not provide the evidence of S. being a carcinogen. In the oral carcinogenicity study with B6C3F₁ mice, a significantly increased incidence of lung tumors (adenoma and carcinomas) was seen in males at the highest dose-level (300 mg/kg BW administered in corn oil). However, in this study the control group was rather small.¹⁷ In a study with Fisher 344 rats,¹⁴ the doses of 500 to 2000 mg/kg BW given in corn oil did not cause any significantly increased tumor incidence. Sprague- Dawley rats received doses of 9 to 250 mg/kg BW in olive oil over a period of 52 weeks. The study was terminated after 140 weeks. No significantly increased tumor incidences were observed.18

A 2-year oral toxicity/carcinogenicity study in conjunction with a three-generation reproduction study was carried out.¹⁰ Rats received 0.125 and 250 mg S./l in their drinking water. No increase tumor incidence was observed. BW loss was noted in a group of females exposed to 250 mg S./l.  No other treatment-related effects were seen. Long-term effects of oral administration were reported. S. was given in olive oil to pregnant female O₂₀ mice (1350 mg/kg BW), C57BL mice (300 mg/kg BW), and BD IV rats (1350 mg/kg BW) on day 17 of gestation. Their offspring were treated weekly throughout their life-span. The incidence of tumors occurring at the sites other than the lung was higher in the untreated mice than in the S.-treated animals. Very high doses, which caused earlier mortality, were used in this study."

The evidence of genotoxicity in short-term animal tests and in humans occupationally exposed to S., along with the data on the metabolite styrene-7,8-oxide, seems to be supportive of carcinogenicity of S. Carcinogenicity classification. IARC: Group 2B; USEPA: Group C; NTP: N^__N^__E^__N.

Chemobiokinetics. S. is readily absorbed and distributed in the body tissues, predominantly in fats. Following inhalation exposure, its content in paranephric fatty cells is ten times higher than in any other tissue.²⁰ S. is shown to enter the liver through the portal vein. It is believed that S. metabolism occurs under the action of liver monooxidase with participation of cytochrome P-450. The monomer is transformed into styrene oxide, which is covalently combined to the macromolecules of hepatocytes and then metabolized to several metabolites, the major ones being mandelic and phenylglyoxylic acids. Both of these metabolites have been detected in the urine of exposed rodents and humans. The nature of the S. metabolites varies according to the species of mammals.=' Unchanged S. in rats is excreted with the exhaled air.

Guidelines. WHO ( 1992): Guideline value for drinking water 0.02 mg/l. The levels of 0.004 to 2.6 mg/l are likely to give rise to consumer complaints of foreign odor and taste.

Standards. USEPA (1991 ). MCL and MCLG: 0.1 mg/l. Russia (1988). MAC and PML: 0.1 mg/l.

Regulations. USFDA ( 1993) approved the use of S. (1) as a component of paper and paperboard for contact with dry food, (2) in semirigid and rigid acrylic and modified acrylic plastics intended for use in food-contact articles, (3) as a component of adhesives to be safely used in food-contact surface, (4) in resinous and polymeric coatings that may be used safely as a food-contact surface of articles intended for use in producing, manufacturing, packing, transporting, or holding food, (5) in polyethylene phthalate polymers to be used safely as articles or components of plastics intended for use in contact with food, and (6) in cross-linked polyester resins used as articles or components of articles intended for repeated contact with food.

References:

1. See ACETONE, #3, 137.

2. Wharton, F. D. and Levinskas, G. l., Chemistry and Industry. 11, June 1976, p. 470.

3. Kataeva, S. Ye., Regulation of the application of polymeric materials in water supply systems used for economic and drinking purposes, Gig. Sanit.. 10, 8, 1988 (in Russian).

4. Petrova, L. I., Investigation of Possible Use of Polystyrene Plastics of Different Composition in Contact with Foodstuffs. Author's abstract of thesis, Leningrad, 1979, p. 20 (in Russian).

5. See -METHYL STYRENE, #1.

6. van Apeldoorn, M. E., van der Heijden, C. A., Heijena-Markus, E., et al., Styrene Criteria Documents. Air Effects Project No. 668310, National Institute of Public Health and Environmental Protection, The Netherlands, 1985.

7. Hussain, R., Srivastava, S. P., Mushtaq, M., et al., Effect of styrene on levels of seratonin. noradrenaline. dopamine, and activity of acetyl cholinesterase and monoamine oxidase in rat brain, Toxicol. Lett., 7, -17, 1980.

8. Srivastava, S. P., Das, h1., Mushtaq, M., et al., Metabolism and genotoxicity of styrene, Adv. Exp. Med. Biol., 136A, 1982.

9. Quast, J. F., Humiston, C. G.. Kalnins, R. V., et al., Results o/ Toxicity Study of Monomeric Styrene Administered to Beagle Dogs by Oral Intubation for 19 Months. Final report, Dow Chemical Co., Midland, MI. 1979.

10. Toxicology Study on Styrene Incorporated in Drinking-Water of Rats for Two Years in Conjunction With a Three Generation Reproduction Study, Styrene, Revised Final Report Weeks I-105, Vol. 1, Litton Bionetics to Chemical Manufacturers Association, 1980.

11. Murray, F. J., John, J. A., Balmer, M. F., et al., Teratologic evaluation of styrene given to rats and rabbits by inhalation or by gavage, Toxicology. 11, 335, 1978.

12. Beliles, R. P., Butala, J. H., Stack, C. R., et al., Chronic toxicity and three-generation reproduction study of styrene monomer in the drinking water of rats, Fundam. Appl. Toxicol., 5, 855, 1985.

13. Hemminki, K., Paasivirta, J., Kurnirinne, T., et al., Alkylation products of DNA bases by simple epoxides, Chem. Biol. Interact.. 30, 259, 1980.

14. Ragul'e, N., Problems concerning the embryotropic effects of styrene, Gig. Sanit., 11, 85, 197-1 (in Russian).

15. IPCS, Environmental Health Criteria 26, Styrene, WHO, Geneva, 1983.

16. Simula, A. P. and Priestly, B. G., Species differences in the genotoxicity of cyclophosphamide and styrene in three in vivo assays, Mutat. Res., 271, 49, 1992.

source: Sheftel, VO. Handbook of Toxic Properties of Monomers and Additives. 1995