Benzene, ethenyl-

Substance overview Plus
Name:
Benzene, ethenyl-
CAS Number:
100-42-5
Synonyms:
Cinnamene, Phenethylene, Phenylethylene, Styrene, Styrol, Vinyl benzene
Approval number:
HSR001221, Approved with controls
UN Class:
Class 3: Flammable liquids; Packing group III: Substances presenting low danger
UN Number:
2055
Molecular weight:
104.2
Relative density:
0.9059
Water solubility:
300 mg/L
Classification Flam. Liquid 3 Plus
Classification route species:
 
Classification description:
H226: Flammable liquid and vapour.
Classification key study:
Flash point: 34.4 °C
Boiling point: 145 °C
Classification Acute Tox. 3 Plus
Classification route species:
(inhalation)
Classification description:
H331: Toxic if inhaled.
Classification key study:

Oral Route
SPECIES: Mouse
ENDPOINT: LD50
VALUE: 316 mg/kg
REFERENCE SOURCE: Progress Report for Contract No. NIH-NCI-E-C-72-3252, Submitted to the National Cancer Institute by Litton Bionetics, Inc. (Bethesda, MD) (NCI-E-C-72-3252,1973). [RTECS]. [IUCLID 2000]

Inhalation Route
SPECIES: Mouse
ENDPOINT: LC50
VALUE: 6.8 mg/l
REFERENCE SOURCE: BASF AG Ludwigshafen (197) BASF AG, Abteilung Toxikologie, unveroeffentlichte Untersuchung (78/259), 22.01.1980 [IUCLID 2000]

Classification Acute Tox. 4 Plus
Classification route species:
(oral)
Classification description:
H302: Harmful if swallowed.
Classification key study:

Oral Route
SPECIES: Mouse
ENDPOINT: LD50
VALUE: 316 mg/kg
REFERENCE SOURCE: Progress Report for Contract No. NIH-NCI-E-C-72-3252, Submitted to the National Cancer Institute by Litton Bionetics, Inc. (Bethesda, MD) (NCI-E-C-72-3252,1973). [RTECS]. [IUCLID 2000]

Inhalation Route
SPECIES: Mouse
ENDPOINT: LC50
VALUE: 6.8 mg/l
REFERENCE SOURCE: BASF AG Ludwigshafen (197) BASF AG, Abteilung Toxikologie, unveroeffentlichte Untersuchung (78/259), 22.01.1980 [IUCLID 2000]

Classification Skin Irrit. 2 Plus
Classification route species:
 
Classification description:
H315: Causes skin irritation.
Classification key study:

Skin Irritation
SPECIES: Rabbit
RESULT: Irritating
REFERENCE SOURCE: REPSOL QUIMICA, S.A. MADRID (215) Union Carbide Data Sheet. 12/13/63
[IUCLID 2000]
REMARK: EC Classification: Irritating

Eye Irritation
R-PHRASE: R 36 Irritating to eyes. [IUCLID 2000].

Classification Eye Irrit. 2 Plus
Classification route species:
 
Classification description:
H319: Causes serious eye irritation.
Classification key study:

Skin Irritation
SPECIES: Rabbit
RESULT: Irritating
REFERENCE SOURCE: REPSOL QUIMICA, S.A. MADRID (215) Union Carbide Data Sheet. 12/13/63
[IUCLID 2000]
REMARK: EC Classification: Irritating

Eye Irritation
R-PHRASE: R 36 Irritating to eyes. [IUCLID 2000].

Classification Repr. 2 Plus
Classification route species:
 
Classification description:
H361: Suspected of damaging fertility or the unborn child <state specific effect if known> <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.
Classification key study:
Effect on fertility: When male rats were exposed to a styrene concentration of 200 mg/m3 (48 ppm) for 5 h/day, 5 days per week for 4 months, Ivanova-Tchemichanska et al. (1982) found decreased osmotic resistance and mobility of spermatozoa, decreased sulfhydryl content, and desquamated epithelium in the seminiferous tubules.
Styrene (EHC 26, 1983)
[INCHEM]
Species: rat Sex: male
Strain: Wistar
Route of admin.: gavage
Exposure period: 60 day
Frequency of treatment: 6 day/week
Post. obs. period: 24 hour
Doses: 200 & 400 mg/kg
Control Group: yes, concurrent vehicle
NOAEL: = 200 mg/kg bw
LOAEL: = 400 mg/kg bw
Method: other
Year: GLP: no data
Test substance: other TS
Remark: Study limited to testicular biochemistry and histopathology, and epididymal sperm counts. -
Result: There was no significant effect upon body weight, testes weight or epididymes weight at either dose. At 400 mg/kg/day styrene caused a significant decrease in sperm count (36%), sorbitol dehydrogenase and acid
phosphatase, and increases in lactate dehydrogenase, gamma-glutamyl transpeptidase, B-glucuronidase and glucose-6-phosphate dehydrogenase.
Hitopathological evaluation of testes from animals in this group showed shrunken seminiferous tubules with damaged nuclei. Some tubules showed extensive loss of germ cells, consisting mainly of Sertoli cells with few spermatogonia.
The interstitium was oedematous with dilated and congested blood vessels.
The results of this study are compatible with damage to maturing germ cells, and loss of spermatozoa through maturation depletion.
Source: BP Chemicals Ltd. London
(255) Srivastava S. et al (1989), Arch Toxicol, 63, 43-46. [iuclid 2000]
Effect on developmental toxicity: When male rats were exposed to a styrene concentration of 200 mg/m3 (48 ppm) for 5 h/day, 5 days per week for 4 months, Ivanova-Tchemichanska et al. (1982) found decreased osmotic resistance and mobility of spermatozoa, decreased sulfhydryl content, and desquamated epithelium in the seminiferous tubules.
Styrene (EHC 26, 1983)
[INCHEM]
Species: rat Sex: male
Strain: Wistar
Route of admin.: gavage
Exposure period: 60 day
Frequency of treatment: 6 day/week
Post. obs. period: 24 hour
Doses: 200 & 400 mg/kg
Control Group: yes, concurrent vehicle
NOAEL: = 200 mg/kg bw
LOAEL: = 400 mg/kg bw
Method: other
Year: GLP: no data
Test substance: other TS
Remark: Study limited to testicular biochemistry and histopathology, and epididymal sperm counts. -
Result: There was no significant effect upon body weight, testes weight or epididymes weight at either dose. At 400 mg/kg/day styrene caused a significant decrease in sperm count (36%), sorbitol dehydrogenase and acid
phosphatase, and increases in lactate dehydrogenase, gamma-glutamyl transpeptidase, B-glucuronidase and glucose-6-phosphate dehydrogenase.
Hitopathological evaluation of testes from animals in this group showed shrunken seminiferous tubules with damaged nuclei. Some tubules showed extensive loss of germ cells, consisting mainly of Sertoli cells with few spermatogonia.
The interstitium was oedematous with dilated and congested blood vessels.
The results of this study are compatible with damage to maturing germ cells, and loss of spermatozoa through maturation depletion.
Source: BP Chemicals Ltd. London
(255) Srivastava S. et al (1989), Arch Toxicol, 63, 43-46. [iuclid 2000]
Classification Muta. 2 Plus
Classification route species:
 
Classification description:
H341: Suspected of causing genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.
Classification key study:
Genetic toxicity in Vitro: In making the overall evaluation, the Working Group took into consideration the following supporting evidence: Styrene is metabolized to styrene-7,8-oxide, which binds covalently to DNA and shows activity in various in-vitro and in-vivo assays for genetic effects. The genetic and related effects of styrene are therefore associated with its oxidation, which also occurs, e.g. in human whole blood cultures, where styrene induces dose-related responses of chromosomal damage at low concentrations. Styrene-7,8-oxide is detected in blood of workers exposed to styrene. Adducts in haemoglobin and DNA, DNA single-strand breaks/alkali-labile sites, as well as significant increases in the frequency of chromosomal damage have been found in workers exposed to styrene in the reinforced plastics industry. Positive results are associated with higher overall styrene levels and negative results with decreasing exposures to styrene. Although in human studies the role of other contaminants cannot be excluded, their occurrence is variable and their concentrations are very low in comparison with that of styrene.
[iarc VOL.: 60 (1994) (p. 233)]
[IARC]

Genetic toxicity in Vivo: In making the overall evaluation, the Working Group took into consideration the following supporting evidence: Styrene is metabolized to styrene-7,8-oxide, which binds covalently to DNA and shows activity in various in-vitro and in-vivo assays for genetic effects. The genetic and related effects of styrene are therefore associated with its oxidation, which also occurs, e.g. in human whole blood cultures, where styrene induces dose-related responses of chromosomal damage at low concentrations. Styrene-7,8-oxide is detected in blood of workers exposed to styrene. Adducts in haemoglobin and DNA, DNA single-strand breaks/alkali-labile sites, as well as significant increases in the frequency of chromosomal damage have been found in workers exposed to styrene in the reinforced plastics industry. Positive results are associated with higher overall styrene levels and negative results with decreasing exposures to styrene. Although in human studies the role of other contaminants cannot be excluded, their occurrence is variable and their concentrations are very low in comparison with that of styrene.
[iarc VOL.: 60 (1994) (p. 233)]
[IARC]

Classification Carc. 2 Plus
Classification route species:
 
Classification description:
H351: Suspected of causing cancer <state route of exposure if it is conclusively proven that no other routs of exposure cause the hazard>.
Classification key study:
Key information: REMARK: Overall evaluation Styrene is possibly carcinogenic to humans (Group 2B).
REFERENCE SOURCE: IARC Monographs; VOL.: 60 (1994) (p. 233)[INCHEM]

Classification STOT Rep. Exp. 1 Plus
Classification route species:
 
Classification description:
H372: Causes damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.
Classification key study:
Repeated dose toxicity:

Oral Route
Primary Organ Effected: Blood and the Hematopoietic system
Secondary Organ(s) Effected: Hepatotoxicity (liver)
Reproductive system
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
Red blood cell and NOAEL: 200 mg/kg-day 1000 1 200 ug/kg-day
liver effects LOAEL: 400 mg/kg-day
Dog Subchronic Oral
Study
Quast et al., 1979 Quast, J.F., C.G. Humiston, R.Y. Kalnins, et al. 1979. Results of a toxicity study of monomeic styrene administered to beagle dogs by oral intubation for 19 months. Toxicology Research Laboratory, Health and Environmental Sciences, DOW Chemical Co., Midland, MI. Final Report
[USEPA IRIS]

Inhalation Route
Endpoint: NOAEL
Value: 0.094
Primary Organ Effected: Neurotoxicity (nervous system)
Also see ATSDR Tox profile
I.B.1. Inhalation RfC Summary:
Critical Effect Exposures* UF MF RfC
-------------------- --------------------------- ----- --- ---------
CNS effects NOAEL: 94 mg/cu.m (25 ppm = 30 1 1E+0 mg/cu.m
150 mmole urinary styrene metabolites/mole creatinine adjusted to lower 95% confidence limit = 22 ppm) Occupational Study NOAEL(HEC): 34 mg/cu.m
Mutti et al. (1984)
LOAEL: >94 mg/cu.m (>22 ppm derived as in NOAEL listing)
--------------------------------------------------------------------------------
*Conversion Factors: MW = 104.15. Assuming 25 C and 760 mmHg, NOAEL
(mg/cu.m) = NOAEL (ppm) x MW/24.45 = 94 mg/cu.m. The NOAEL exposure level is
based on a back extrapolation from worker urinary concentration of styrene
metabolites reported in the principal study and adjusted to the lower 95%
confidence limit listed in Guillemin et al. (1982), which was 88%, 25 ppm x
0.88 = 22 ppm. The NOAEL(HEC) is calculated using an 8-hour TWA occupational
exposure. MVho = 10 cu.m/day, MVh = 20 cu.m/day. NOAEL(HEC) = 94 mg/cu.m x
MVho/MVh x 5 days/7 days = 34 mg/cu.m. The feasibility of applying the
exposure model of Perbellini et al. (1988) for extrapolation of the values in
the principal study is currently being investigated. Application of this
model may result in changes in the NOAEL(HEC) value and, therefore, the RfC.
Mutti, A., A. Mazzucchi, P. Rusticelli, G. Frigeri, G. Arfini, and I. Franchini. 1984. Exposure-effect and exposure-response relationships between occupational exposure to styrene and neuropsychological functions. Am. J. Ind. Med. 5: 275-286.
[USEPA IRIS]
In a cross-sectional study, Mutti et al. (1984) examined the neuro-psychological function in 50 workers whose mean duration of styrene exposure was 8.6 (SD of 4.5) years. Styrene exposure was assessed by the authors to correspond to air concentrations ranging from 10-300 ppm as a mean daily exposure. These concentrations were estimated from the summation of the principal urinary metabolites of styrene, mandelic acid (MA) and phenylglyoxylic acid (PGA). Urinary metabolite levels are considered as reliable biological indicators of styrene exposure (ACGIH, 1986; WHO, 1983), and several laboratories have determined collectively that the specific method used in this study, the summation of the principal metabolites collected in next-morning urine, is the most reliable and representative of actual air exposure concentrations (Guillemin et al., 1978, 1982; Ikeda et al., 1982; Franchini et al., 1983). Workers with absence of metabolic and neurologic disorders, smoking habits of <20 cigarettes/day, and an alcohol intake of <80 mL of ethanol/day were chosen. These same eligibility criteria were used to select a control group of 50 workers that was matched for age, sex, and educational level. The exposed workers were further segregated into four subgroups (n = 9-14) according to increasing levels of urinary styrene metabolites. A battery of neuropsychological tests was conducted on the same day as the urine collection and included exams evaluating visuo-motor speed, memory, and intellectual function. No other endpoints were considered. Correlation analysis of the test results and urinary metabolite levels showed a clear concentration response in at least three of eight tests, including block design (intellectual function), digit-symbol (memory), and reaction times (visuo-motor speed). Evidence of a concentration-response relationship was also present for short- and long-term logical memory and embedded figures (impaired visual perception). When the results were analyzed using duration
of exposure as a covariate, increases in reaction times and a decrease in digit symbol (memory, concentration) were apparent. The only test showing results in the lowest exposure group, short-term verbal memory loss, exhibited no concentration-response relationship. The neuropsychological results from this study are from established tests for CNS dysfunction, are present when compared against a stringently matched control population, and show concentration-response relationships. Also, the deficiencies noted in the reaction-times corroborate the results presented by Moller et al. (1990) and others discussed below.
The concentration-response relationship between urinary metabolite concentration (mandelic acid and phenylglyoxylic acid levels normalized to creatinine in "morning-after" urine) and test results indicated a significant effect level in the subgroup whose urine contained 150-299 mmole urinary metabolites/mole creatinine. Workers with metabolite concentrations of up to
150 mmoles/mole appeared to have no significant effects, and this level is therefore designated as the NOAEL in this study. The authors state that this level of urinary metabolites corresponds to a mean daily 8-hour exposure to air styrene of 25 ppm (106 mg/cu.m). Derivation of this air level is from the creatinine-normalized, combined concentration of the styrene metabolites, MA and PGA, in urine collected from the workers on Saturday mornings. Guillemin et al. (1982) demonstrated a logarithmic relationship (r = 0.871) between the summation of urinary metabolites (MA + PGA, next morning) and air concentrations of styrene (ppm x hours). Guillemin calculated the mean combined urinary metabolite concentration (next morning) for an 8-hour exposure to 100 ppm. This relationship was used by both Mutti et al. (1984) and Guillemin and Berode (1988) in a proportional manner to obtain styrene air levels at lower urinary metabolite concentrations. The 95% confidence interval was also calculated for an 8-hour exposure at 100 ppm, the lower limit of the confidence calculation being 88% of the mean styrene exposure. This factor was applied directly to the NOAEL of 25 ppm [25 ppm x 0.88 = 22 ppm (94 mg/cu.m)]. Due to the construction of the subgroups, designation of a LOAEL was the lower limit of the subgroup in which adverse effects were observed
[i.e., greater than the NOAEL of 22 ppm (94 mg/cu.m)].
[USEPA - IRIS]

Classification Aquatic Acute 1 Plus
Classification route species:
 
Classification description:
H400: Very toxic to aquatic life.
Classification key study:
Bioaccumulation: Bioaccumulative: No
log Pow: = 2.96
Method: OECD Guideline 107 "Partition Coefficient (n-octanol/water),
Flask shaking Method"
Year: 1981
GLP: no data
Source: BP Chemicals Ltd. London
(41) BASF AG, analytical laboratory report, unpublished data (BRU 87.206).
[IUCLID 2000]

Biodegradation in water: readily biodegradable
Short term toxicity to fish: SPECIES: Cyprinodon variegatus (Sheepshead minnow)
TYPE OF EXPOSURE: Static
DURATION: 96 hr
ENDPOINT: LC50 (Mortality)
VALUE: 9.1 mg/L
REFERENCE SOURCE: Ref No: 10366. Heitmuller, P.T., T.A.Hollister, and P.R.Parrish (1981) Acute Toxicity of 54 Industrial Chemicals to Sheepshead Minnows (Cyprinodon variegatus). Bull. Environ. Contam. Toxicol. 27(5):596-604 [ECOTOX]

Short term toxicity to invertebrates: SPECIES: Daphnia magna (Crustacea)
TYPE OF EXPOSURE: Flow through
DURATION: 48 hr
ENDPOINT: EC50
VALUE: 4.7 mg/l
REFERENCE SOURCE: BASF AG Ludwigshafen (145) Springborn Laboratories, Inc., Report No.95-6-5945, 14.09.1995 [IUCLID 2000]

Toxicity to freshwater algae and cyanobacteria: SPECIES: Selenastrum capricornutum (Algae)
TYPE OF EXPOSURE:
DURATION: 96 hr
ENDPOINT: EC50
VALUE: 0.72 mg/l
REFERENCE SOURCE: BASF AG Ludwigshafen
(161) Springborn Laboratories, Inc., Report No.95-6-5933, 14.09.1995 [iuclid 2000]