Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 246-562-2 | CAS number: 25013-15-4
Endpoint summary
Administrative data
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Effects on fertility
Description of key information
Toxicity to Reproduction (Screening): In accordance with Column 2 of ANNEX VIII of the REACH regulation, screening for reproductive/developmental toxicity study does not need to be conducted as a pre-natal developmental toxicity study is available.
Extended one-generation reproductive toxicity: In accordance with Column 2 of ANNEX IX of the REACH regulation, a extended one-generation reproductive toxicity study does not need not to be conducted as the existing repeated dose toxicity study does not indicate adverse effects on reproductive organs or tissues.
Link to relevant study records
- Endpoint:
- extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- the extended one-generation reproductive toxicity study does not need to be conducted because there are no results from available repeated dose toxicity studies that indicate adverse effects on reproductive organs or tissues, or reveal other concerns in relation with reproductive toxicity
- Endpoint:
- screening for reproductive / developmental toxicity
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Reason / purpose for cross-reference:
- data waiving: supporting information
- Reason / purpose for cross-reference:
- data waiving: supporting information
- Reason / purpose for cross-reference:
- data waiving: supporting information
- Reproductive effects observed:
- not specified
Referenceopen allclose all
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Toxicity to Reproduction (Screening): In accordance with Column 2 of ANNEX VIII of the REACH regulation, screening for reproductive/developmental toxicity study does not need to be conducted as a pre-natal developmental toxicity study is available.
Extended one-generation reproductive toxicity: In accordance with Column 2 of ANNEX IX of the REACH regulation, a extended one-generation reproductive toxicity study does not need not to be conducted as the existing repeated dose toxicity study does not indicate adverse effects on reproductive organs or tissues.
Effects on developmental toxicity
Description of key information
Pre-natal developmental toxicity study (rat, oral):
NOAEL for maternal/foetotoxicity toxicity: 600 mg/kg bw/day.
NOAEL for embryotoxicity/teratogenicity: 600 mg/kg bw/day.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Read-across justification attached below.
- Reason / purpose for cross-reference:
- read-across source
- Species:
- rat
- Strain:
- CD-1
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Compared to the control group there was a reduction in maternal weight gain in all treated groups.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- >= 600 mg/kg bw/day (nominal)
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- mortality
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- effects observed, non-treatment-related
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No malformations were observed in the control, 50 or 300 mg/kg/day groups. One malformation,
meningocele, was observed in one fetus from one litter in the 600 mg/kg/day. The number of
fetuses and litters with genetic or developmental variations in all treated groups was comparable to the control group. - Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- >= 600 mg/kg bw/day (nominal)
- Basis for effect level:
- reduction in number of live offspring
- fetal/pup body weight changes
- external malformations
- skeletal malformations
- visceral malformations
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Treatment with 4-methylstyrene did not produce a teratogenic response when administered orally to pregnant rats at a dosage level of 600 mg/kg/day or less.The target substance is also predicted to be not teratogenic.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- according to guideline
- Guideline:
- other: Not referenced
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- Sexually mature, virgin female Charles River COBS CD rats (approximately 12 weeks old).
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Remarks:
- Dose volume of 5 mL/kg
- Details on exposure:
- Beginning on day 6 of gestation and continuing daily through day 19 of gestation, the test substance was suspended in corn oil and administered by oral gavage (volume, 5.0 ml/kg) to pregnant females at a single daily dose of 50, 300, and 600 mg/kg/day. A control group received the vehicle only on comparable regimen at a volume of 5 ml/kg.
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Sexually mature, virgin female Charles River COBS CD rats (approximately 12 weeks old) were mated in 1:1 with males in sufficient numbers to assign a minimum of 25 pregnant animals per group.
- Duration of treatment / exposure:
- seven days/week
- Frequency of treatment:
- Once daily
- Duration of test:
- 20 days after gestation
- Dose / conc.:
- 600 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 25 females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Sexually mature, virgin female Charles River COBS CD rats (approximately 12 weeks old) were mated in 1:1 with males in sufficient numbers to assign a minimum of 25 pregnant animals per group. Beginning on day 6 of gestation and continuing daily through day 19 of gestation, the test substance was suspended in vehicle and administered by oral gavage (volume, 5.0 ml/kg) to pregnant females at a single daily dose of 50, 300, and 600 mg/kg/day. A control group received the vehicle only on a comparable regimen at a volume of 5 ml/kg.
- Maternal examinations:
- mortality(Prior to treatment and GD 6 to 19)
appearance and behavior(Prior to treatment )
clinical signs (GD 6 to 19)
body weights (GD 0 to 20) - Ovaries and uterine content:
- organ weight, the number and location of viable and nonviable fetuses, early and late resorptions, and the number of total implantations and corpora lutea
- Fetal examinations:
- weight, examined for external malformations and variations, including the palate and eyes. Each
fetus was externally sexed and individually numbered and tagged for identification. Approximately one-half of the fetuses were placed in Bouin’s fixative for subsequent visceral examination by razor-blade sectioning. The remaining one-half of the fetuses were fixed in alcohol, macerated in potassium hydroxide and stained with Alizarin Red S for subsequent skeletal examination. - Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Compared to the control group there was a reduction in maternal weight gain in all treated groups.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- >= 600 mg/kg bw/day (nominal)
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- mortality
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- effects observed, non-treatment-related
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No malformations were observed in the control, 50 or 300 mg/kg/day groups. One malformation, meningocele, was observed in one fetus from one litter in the 600 mg/kg/day. The number of
fetuses and litters with genetic or developmental variations in all treated groups was comparable to the control group. - Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- >= 600 mg/kg bw/day (nominal)
- Basis for effect level:
- reduction in number of live offspring
- fetal/pup body weight changes
- external malformations
- skeletal malformations
- visceral malformations
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Under the study conditions, the NOAEL for teratogenicity was established at 600 mg/kg bw/day.
- Executive summary:
A study was conducted to determine the teratogenic potential of the read across substance, 4-methylstyrene. Groups of 25 pregnant Charles River COBS CD rats were given the test substance by oral gavage (volume, 5.0 ml/kg), from Gestation Day (GD) 6 to 19 at a single daily dose of 50, 300, and 600 mg/kg/day. A control group received the vehicle only, olive oil, at a dose volume of 5 mL/kg bw.
There were no mortalities or clinical signs in the maternal groups. Compared to controls, there was a reduction in maternal weight gain in all treated groups and this was considered not statistically significant. Fetal weights in all treated groups were also significantly lower than the controls. However, this may have been the results of an unusually high control value for fetal weight, above the normal background range of the laboratory. There were no biologically meaningful differences in the mean number of corpora lutea, total implantations, early or late resorptions, post implantation loss, viable fetuses, fetal sex distribution, mean fetal body weight or number of fetuses (and litters) with malformations.
Under the study conditions, the NOAEL for teratogenicity was established at 600 mg/kg bw/day.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- according to guideline
- Guideline:
- other: Not referenced
- GLP compliance:
- not specified
- Limit test:
- yes
- Specific details on test material used for the study:
- no available
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- Female
- Route of administration:
- intraperitoneal
- Vehicle:
- corn oil
- Details on exposure:
- Female rats injected intraperitoneally with the test chemical dissolved or suspended in corn oil at 250 mg/kg (MTD, maximum tolerated dose) .
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- After the MTD determination, young adult female Sprague-Dawley rats (250-300 g) were caged with breeder males of the same strain. The females were examined daily for the presence of sperm in a vaginal lavage. The day sperm was detected was designated as day 1 of gestation. Inseminated females were randomly assigned to treatment and control groups.
- Duration of treatment / exposure:
- 15days
- Frequency of treatment:
- daily for 15 days
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10-15
- Details on study design:
- Young adult female Sprague-Dawley rats (250-300 g) were caged with breeder males of the same strain. The females were examined daily for the presence of sperm in a vaginal lavage. The day sperm was detected was designated as day 1 of gestation. Inseminated females were randomly assigned to treatment and control groups. Treatment began on day 1 of gestation and continued through day 15. Controls were injected intraperitoneally with corn oil, while the test group received the test chemical in corn oil at the MTD (250 mg/kg). Each group was composed of 10-15 inseminated females individually housed in stainless steel wire mesh cages with free access to food and water.
On day 21 of gestation, the females were killed by decapitation and the uterine contents were examined. The individual fetuses were weighed, measured for crown-rump length, sexed, and examined for externally visible malformations. One-half to two-thirds of each litter was preserved in Bouin’s fluid for internal examination by the Wilson method of free-hand razor-blade sectioning, and the balance of each litter was preserved in ethanol for clearing and skeletal staining with alizarin red. The internal organs of the maternal rats were examined grossly, and the brain, heart, lungs, liver, spleen, kidneys, adrenals, and ovaries were weighed and then preserved in 10% formalin for histopathological examination. - Ovaries and uterine content:
- On day 21 of gestation, the females were killed by decapitation and the uterine contents were examined.
- Fetal examinations:
- The individual fetuses were weighed, measured for crown-rump length, sexed, and examined for externally visible malformations;
internal examination;
skeletal examination. - Statistics:
- Fisher’s exact test
- Clinical signs:
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not examined
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Histopathological findings: neoplastic:
- not specified
- Number of abortions:
- not examined
- Pre- and post-implantation loss:
- not examined
- Total litter losses by resorption:
- not examined
- Early or late resorptions:
- not examined
- Dead fetuses:
- not examined
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- not examined
- Details on maternal toxic effects:
- The incidence of resorptions was significantly increased (p<0.05), No teratogenic effects were observed. In addition, no treatment-related histopathological changes were observed in maternal tissues.
- Dose descriptor:
- LOAEL
- Effect level:
- 250 mg/kg bw/day (nominal)
- Basis for effect level:
- early or late resorptions
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- not specified
- Reduction in number of live offspring:
- not examined
- Changes in sex ratio:
- effects observed, treatment-related
- Description (incidence and severity):
- fetal sex ratio was significantly altered (p<0.05) with a deficit of female fetuses
- Changes in litter size and weights:
- not examined
- Anogenital distance of all rodent fetuses:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- not specified
- Skeletal malformations:
- not specified
- Visceral malformations:
- not specified
- Dose descriptor:
- LOAEL
- Effect level:
- 250 mg/kg bw/day (actual dose received)
- Basis for effect level:
- changes in sex ratio
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- The substance is non-teratogenic.
- Executive summary:
In the pre-natal developmental toxicity study( Hardin BD,1981),female Sprague-Dawley rats was daily intraperitoneally administrated with the test chemical dissolved or suspended in corn oil at 250 mg/kg for 15 days.
The incidence of resorptions was significantly increased (p<0.05), and the fetal sex ratio was significantly altered (p<0.05) with a deficit of female fetuses. No teratogenic effects were observed. In addition, no treatment-related histopathological changes were observed in maternal tissues.
The substance is non-teratogenic.
Referenceopen allclose all
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 600 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The key study was well documented, and meets generally accepted scientific principles and was assigned a Klimisch score of 2. The overall quality of the database is high.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
A study was conducted to determine the teratogenic potential of the read across substance, 4-methylstyrene. Groups of 25 pregnant Charles River COBS CD rats were given the test substance by oral gavage (volume, 5.0 ml/kg), from Gestation Day (GD) 6 to 19 at a single daily dose of 50, 300, and 600 mg/kg/day. A control group received the vehicle only, olive oil, at a dose volume of 5 mL/kg bw.
There were no mortalities or clinical signs in the maternal groups. Compared to controls, there was a reduction in maternal weight gain in all treated groups and this was considered not statistically significant. Fetal weights in all treated groups were also significantly lower than the controls. However, this may have been the results of an unusually high control value for fetal weight, above the normal background range of the laboratory. There were no biologically meaningful differences in the mean number of corpora lutea, total implantations, early or late resorptions, post implantation loss, viable fetuses, fetal sex distribution, mean fetal body weight or number of fetuses (and litters) with malformations.
Under the study conditions, the NOAEL for teratogenicity was established at 600 mg/kg bw/day.
Justification for classification or non-classification
Based on the available information in the dossier, the substance Vinyltoluene does not need to be classified for reproductive toxicity when the criteria outlined in Annex I of 1272/2008/ EC are applied.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
