Registration Dossier
Registration Dossier
Diss Factsheets
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
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Endpoint summary
Administrative data
Description of key information
Acute oral toxicity:
LD50 (rat) = 2321.58 mg/kg bw (QSAR; 3-methylstyrene, CAS no. 100-80-1)
LD50 (male rat) = 4000 mg/kg bw (No guideline; Vinyl toluene, CAS No. 25013-15-4)
LD50 (rat) = 2255 mg/kg bw (No guideline; 4-Methylstyrene, CAS No. 622-97-9)
Acute inhalation toxicity: LC50 (male/female) = >5.02 mg/L (OECD 403/GLP)
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Guideline:
- other: REACH guidance on QSARs R.6
- Principles of method if other than guideline:
- - Software tool(s) used including version: T.E.S.T. (Toxicity Estimation Software Tool; version 4.2.1)
- Model(s) used: T.E.S.T. Oral rat LD50 4.2.1
- Model description: Endpoint represents the amount of the chemical (mass of the chemical per body weight of the rat) which when orally ingested kills half of rats.
Reference(s) to main scientific papers and/or software package:
Martin, T; Toxicity Estimation Software Tool (TEST); U.S. Environmental Protection Agency,
Washington, DC, (2016)
https://www.epa.gov/chemical-research/toxicity-estimation-software-tool-test - Specific details on test material used for the study:
- CC1=CC=CC(C=C)=C1
- Species:
- rat
- Route of administration:
- oral: unspecified
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 2 321.58 mg/kg bw
- Remarks on result:
- other: QSAR predicted value
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute oral LD50 of 3-methylstyrene(CAS No.100-80-1) was predicted as 2321.58 mg/kg.
- Executive summary:
The predicted LD50 is 2321.58 mg/kg based on Consensus, which can be concluded as not classified for acute oral toxicity. The results of the model can be considered reliable in terms of numerical value because the closest neighbours in the test set and training set predicted accurately and both MAE of similar compounds in the test/training set lower than the error observed for the whole dataset. Although the predicted value of the most similar chemical CAS No. 622- 97-9 is slightly lower than experiment value, the difference ≤0.5, which is acceptable.
Reference
4. Defining the algorithm - OECD Principle 2
4.2. Explicit algorithm
Hierarchical method: The toxicity for a given query compound is estimated using the weighted average of the predictions from several different models. The different models are obtained by using Ward’s method to divide the training set into a series of structurally similar clusters. A genetic algorithm based technique is used to generate models for each cluster. The models are generated prior to runtime. FDA method: The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime. Nearest neighbour method: The predicted toxicity is estimated by taking an average of the 3 chemicals in the training set that are most similar to the test chemical. Consensus method: The predicted toxicity is estimated by taking an average of the predicted toxicities from the above QSAR methods (provided the predictions are within the respective applicability domains).
5. Defining the applicabilitv domain - OECD Principle 3
5.1. Description of the applicability domain of the model:
Hierarchical method: The applicability domain is defined using several different constraints. The first constraint, the model ellipsoid constraint, checks if the test chemical is within the multidimensional ellipsoid defined by the ranges of descriptor values for the chemicals in the cluster (for the descriptors appearing the cluster model). The second constraint, the Rmax constraint, checks if the distance from the test chemical to the centroid of the cluster is less than the maximum distance for any chemical in the cluster to the cluster centroid. The last constraint, the fragment constraint, is that the compounds in the cluster have to have at least one example of each of the fragments contained in the test chemical. For example if one was trying to make a prediction for ethanol, the cluster must contain at least one compound with a methyl fragment (- CH3 [aliphatic attach]), one compound with a methylene fragment (-CH2 [aliphatic attach]), and one compound with a hydroxyl fragment (-OH [aliphatic attach]). This constraint was added to avoid situations where a chemical might have a similar backbone structure to the chemicals in a given cluster but has a different functional group attached. For example if a given cluster contained only short-chained aliphatic amines one would not want to use it to predict the toxicity of ethanol. If a chemical contains a fragment that is not present in the training set, the toxicity cannot be predicted. The fragment constraint can be removed before execution.
FDA method: For a prediction to be valid, the cluster must not violate the model ellipsoid and fragment constraints described above (for Hierarchical method). In addition, the predicted toxicity value must be within the range of experimental toxicity values for the chemicals used to build the model.
Nearest neighbour method: In order to make a prediction, each of the structural analogs must exceed a certain minimum cosine similarity coefficient (SCmin). SCmin was set at 0.5 so that the prediction coverage was similar to that of the other QSAR methods.
Consensus method: In the consensus method, the predicted toxicity is simply the average of the predicted toxicities from the other QSAR methodologies (taking into account the applicability domain of each method).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- > 2 000 mg/kg bw
- Quality of whole database:
- The quality of the database is high as there is QSAR data and 2 in vivo studies available.
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 25 November 2020 – 9 September 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.2 (Acute Toxicity (Inhalation))
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- traditional method
- Limit test:
- yes
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: Provided by Sponsor, Batch no.: 20200608
- Expiration: 07 August 2021
- Purity, including information on contaminants, isomers, etc.: 99.66% (3-Vinyltoluene CAS No. 100-80-1: 64.3 %; 4-Vinyltoluene CAS No. 622-97-9: 35.7 %)
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Stored at +2 °C to +8 °C in a tightly closed container - Species:
- rat
- Strain:
- other: Crl: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories,Research Models and Services, Germany GmbH, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Males: 49 days; Females: 63 days
- Housing: During the 14-day observation period the animals are caged by sex in groups of 2 or 3 by sex in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, Goldenstedt, Germany) is used as bedding material for the cages. The cages are changed and cleaned twice a week.
- Diet: Commercial diet ssniff® R/M-H V1534 served as food (ssniff Spezialdiäten GmbH, 59494 Soest, Germany). This food was offered ad libitum. Food residue was removed.
- Water: Tap water was offered ad libitum.
Acclimitisation period: 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 55% ± 10%
- Air changes (per hr): air changes/h (≥12)
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Mass median aerodynamic diameter (MMAD):
- ca. 9.205 µm
- Geometric standard deviation (GSD):
- ca. 4.913
- Remark on MMAD/GSD:
- Feasibility tests:
1st: 5.20 mg/L air MMAD = 9.124 µm GSD = 5.443;
2nd: 2.06 mg/L air MMAD = 9.768 µm GSD = 2.057.
The feasibility tests revealed that the MMAD at a concentration of 2 mg/L air was even slightly worse compared to a concentration at 5 mg/L air. The cumulative mass of particles less than 4 µm was approximately 31% at a concentration at 5 mg/L air and only 11% at a concentration at 2 mg/L air. Hence, the use of 5 mg/L air is from a toxicological point of view more suitable than employing 2 mg/L air, as at a concentration of 5 mg/L air the absolute concentration of smaller particles reaching the alveoli is considered to be larger than at 2 mg/L air.
Limit test:
Nominal concentration: 49.88 mg/L air;
Gravimetric (actual) concentration: 5.02 ± 0.02 mg/L air;
Mean MMAD: 9.205 µm;
Mean GSD: 4.913. - Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Feasibility test:
Before initiating the study with the animals, a feasibility test was carried out with the exposure system in order to verify that under the experimental settings chosen, the limit concentration of 5 mg/L air could be achieved by gravimetric analysis. The assay confirmed the functionality of the inhalation system and a limit concentration of 5.20 mg/L air was achieved. The determination of the aerosol particles at a concentration of 5 mg/L air revealed a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) out of the recommended range of 1 - 4 µm for MMAD and 1.5 - 3.0 for GSD as recommended in the OECD guideline 403. Hence, a further feasibility test was carried out with a limit concentration of 2 mg/L air.
The feasibility tests revealed that the MMAD at a concentration of 2 mg/L air (9.768 µm) was even slightly worse compared to a concentration at 5 mg/L air (9.124 µm). The cumulative mass of particles less than 4 µm was approximately 31% at a concentration at 5 mg/L air and only 11% at a concentration at 2 mg/L air. Hence, the use of 5 mg/L air is from a toxicological point of view more suitable than employing 2 mg/L air, as at a concentration of 5 mg/L air the absolute concentration of smaller particles reaching the alveoli is considered to be larger than at 2 mg/L air. For results of the feasibility tests, see Appendix 3.
- Exposure apparatus: The study was carried out using a dynamic inhalation apparatus (RHEMA-LABORTECHNIK, 65719 Hofheim/Taunus, Germany; air changes/hour approximately 30 times). The apparatus consists of a cylindrical exposure chamber which holds the animals in pyrex tubes at the edge of the chamber in a radial position.
- Exposure chamber volume: 28.5 L (Inner Diameter: 23.9 cm; Height: 63.0 cm)
- Method of holding animals in test chamber: The study animals were acclimatised to the test apparatus for approximately 5 minutes on 3 days prior to testing. The restraining tubes did not impose undue physical, thermal or immobilisation stress on the animals. Exposition started by locating the animals into the exposure chamber after equilibration of the chamber concentration for at least 15 minutes. Nose-only exposure was carried out according to KIMMERLE & TEPPER.
- Source and rate of air (airflow): A manometer and an air-flow meter (ROTA Yokogawa GmbH & Co. KG, 79664 Wehr/Baden, Germany) were used to control the constant supply of compressed air (inflow 900 L/h) and the exhaust (outflow 800 L/h), respectively. Flow rates were checked hourly and corrected if necessary.
Method of conditioning air: The oxygen content in the inhalation chamber was 21%. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set . No determination of the carbon dioxide concentration was carried out as there was no evidence that the CO2 concentration exceeded 1% during the exposure.
- System of generating particulates/aerosols: The aerosol of the test item was obtained using a spray-jet (ALUP Kompressorenfabrik, 73257 Köngen, Germany). The spray-jet was fed with compressed air (5.0 bar) from a compressor and with the test item using an infusion pump (TSE infustion pump no. 37, jet model no. 970, TSE Systems). At the bottom of the exposure chamber, the air was sucked off at a lower flow rate than it was created by the spray-jet in order to produce a homogenous distribution and a positive pressure in the exposure chamber.
- Method of particle size determination: An analysis of the particle size distribution was carried out twice during the exposure period (80 minutes and 160 minutes after start of exposure) using a cascade impactor according to May.
The impactor is a device that classifies particles present in a sample of air or gas into known size ranges by drawing the air sample through a cascade of progressively finer nozzles. The air jets from this impact on pre-weighed plane sampling surfaces (slides). Each stage represents an aerodynamic size range and collects finer particles than its predecessor. Each successive stage represents a special aerodynamic cut-off diameter.
The aerosol from the exposure chamber is sucked through the cascade impactor for a specified period of time at a constant flow rate which depends on the physical properties of the test item. Aerosols with mass median aerodynamic diameter (MMAD) ranging from 1 to 4 µm with a geometric standard deviation (σg) in the range of 1.5 to 3.0 are recommended to allow the exposure of all relevant regions of the respiratory tract.
In the present study, the aerosol from the exposure chamber was drawn through the cascade impactor for 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance with a precision of 0.1 mg. Deltas of slides’ weight were determined. The mass median aerodynamic diameter (MMAD) was estimated by means of non-linear regression analysis. The 32 µm particle size range and the filter (particle size range < 0.5 µm) were not included in the determination of the MMAD in order not to give undue weight to these values. The Geometric Standard Deviation (GSD) of the MMAD was calculated from the quotient of the 84.1%- and the 50%-mass fractions, both obtained from the above-mentioned non-linear regression analysis.
- Temperature, humidity in air chamber: The correct temperature (22°C ± 3°C) and humidity (55% ± 15%) in the inhalation chamber were checked once every hour with a climate control monitor.
TEST ATMOSPHERE
The actual aerosol concentration in the inhalation chamber was measured gravimetrically with
an air sample filter (0.45 µm; Minisart SM 17598) and pump (Membrane Pump,Vacuubrand GmbH
+ Co. KG, 97877 Wertheim/Main, Germany) controlled by a rotameter (Rota Yokogawa Deutschland GmbH, 40880 Rattingen, Germany). Aerosol samples were taken once every hour during the exposure. For that purpose, a probe was placed close to the animals' noses and air was drawn through the air sample filter at a constant flow of air of 5 L/min for 60 seconds. The filters were weighed before and after sampling (accuracy 0.1 mg). Individual chamber concentration samples did not deviate from the mean chamber concentration by more than 1%. In the report, both the nominal and the gravimetric concentrations are given, the inhalation chamber was equilibrated for at least 15 minutes.
TEST ATMOSPHERE (if not tabulated)
Limit test:
Nominal concentration: 49.88 mg/L air;
Gravimetric (actual) concentration: 5.02 ± 0.02 mg/L air;
Mean MMAD: 9.205 µm;
Mean GSD: 4.913. - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- Main test:
Target concentration = 5 mg/L air;
Gravimetric (actual) concentration = 5.02 ± 0.02 mg/L air - No. of animals per sex per dose:
- 3
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days: yes
- Frequency of observations and weighing: A careful clinical observation of each animal was made on the day of exposure (i.e. test day 1) and frequently during the treatment period, at least twice thereafter. Further observations were made at least once daily for 14 days or longer, if necessary. Records were maintained for each animal and any occurrence of findings. Observations on mortality were made at least once daily (in the morning starting on test day 2) to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Individual body weights of animals were determined once during the adaptation period on test day -1, before the exposure on test day 1, and on test days 4, 8, 15 and at time of death. Changes in weight were calculated and recorded in case of survival exceeded one day.
- Necropsy of survivors performed: Necropsy of all animals was carried out and all gross pathological changes were recorded. The lung weights of all animals were determined.
- Clinical signs including body weight : Cageside observations included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system as well as somatomotor activity and behaviour pattern. Particular attention was directed to observations in form of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The animals were also observed for possible indications of respiratory irritation such as dyspnoea (shortness of breath, observed in form of a reduced respiratory rate). - Preliminary study:
- The feasibility tests revealed that the MMAD at a concentration of 2 mg/L air (9.768 µm) was even slightly worse compared to a concentration at 5 mg/L air (9.124 µm). The cumulative mass of particles less than 4 µm was approximately 31% at a concentration at 5 mg/L air and only 11% at a concentration at 2 mg/L air. Hence, the use of 5 mg/L air is from a toxicological point of view more suitable than employing 2 mg/L air, as at a concentration of 5 mg/L air the absolute concentration of smaller particles reaching the alveoli is considered to be larger than at 2 mg/L air. For results of the feasibility tests, see Appendix 3.
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 5.02 mg/L air
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: 5.02 ± 0.02 mg/L air
- Mortality:
- The test item led to mortality/morbidity in only 1 of the 6 animals. One female rat revealed a pronounced sedation until 60 minutes p.a. and was sacrificed prematurely 2 hours after end of exposure due to animal welfare reasons.
- Clinical signs:
- other: Refer to Any other information on results incl. tables
- Body weight:
- The body weight did not reveal test item-related changes in any of the rats at the end of the study.
- Gross pathology:
- The macroscopic examination at necropsy did not reveal any changes. Hence, no histopathological examination was performed. No influence on the lung weights was observed.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In an acute inhalation toxicity study in male/female Crl: CD(SD) rats, the LC50 of Vinyltoluene was > 5.02 mg/L air.
- Executive summary:
In an acute inhalation toxicity study (OECD 403/GLP), a group of young adult Crl: CD(SD) rats (3/sex) were exposed to a test atmosphere of Vinyltoluene (99.66%; 3-Vinyltoluene CAS No. 100-80-1: 64.3 %; 4-Vinyltoluene CAS No. 622-97-9: 35.7 %) in air (aerosol) for 4 hours (nose only) at the target concentration of 5 mg/L air (limit test). Animals were then observed for 14 days.
LC50 male/female > 5.02 mg/L air.
The determination of the aerosol particle distribution did not reveal the range for MMAD (1 - 4 µm) and GSD (1.5 - 3.0) as recommended in the guideline. The feasibility tests revealed that the MMAD at a concentration of 2 mg/L air (9.768 µm) was even slightly worse compared to a concentration at 5 mg/L air (9.124 µm).The cumulative mass of particles less than 4 µm was approximately 31% at a concentration at 5 mg/L air and only 11% at a concentration at 2 mg/L air. Hence, the use of 5 mg/L air is from a toxicological point of view more suitable than employing 2 mg/L air, as at a concentration of 5 mg/L air the absolute concentration of smaller particles reaching the alveoli is considered to be larger than at 2 mg/L air. The gravimetric (actual) concentration in the limit test was 5.02 ± 0.02 mg/L air. The mean MMAD and GSD were 9.205 μm and 4.913, respectively.
The test item led to mortality/morbidity in only 1 of the 6 animals. One female rat revealed a pronounced sedation until 60 minutes p.a. and was sacrificed prematurely 2 hours after end of exposure due to animal welfare reasons. Systemic toxicity was noted in in form of reduced motility, ataxia, tremor, a reduced respiratory rate, tonic and clonic convulsions, and/or lacrimation immediately after end of exposure up to 3 hours after end of exposure in all 3 of 3 male and up to 3 of 3 female animals. Pilo-erection was noted up to 48 hours after end of exposure. The body weight did not reveal test item-related changes in any of the rats at the end of the study.The macroscopic examination at necropsy did not reveal any changes. Hence, no histopathological examination was performed. No influence on the lung weights was observed.
Reference
Clinical signs
The following signs of systemic toxicity occurred in all 3 male and 3 female animals immediately after end of the 4-hour exposure and lasted for up to test day 3:
Moderately to severely reduced motility and ataxia were noted in all male and female rats until 60 minutes p.a., and slightly reduced motility and ataxia until 3 hours p.a.
Slightly reduced respiratory rates, tonic and clonic convulsions and slight tremor were observed in all 3 male and 2 of 3 female animals until 3 hours p.a. Slight lacrimation was observed for all animals up to 3 hours p.a. One female rat (no. 5 f) revealed a pronounced sedation until 60 minutes p.a. and was sacrificed prematurely 2 hours after end of exposure due to animal welfare reasons.
Slight pilo-erection was noted up to test day 2 (all 3 females) or test day 3 (all 3 males) p.a.
Furthermore, the following sign of systemic toxicity occurred in 1 of 3 female animals in test week 2 p.a.:
Ptosis and corneal oedema was noted in female no. 6 f on test day 8 or 9 and lasted until test day 11 or 13, respectively.
Feasibility test results summary
Feasibility test
| Initial concentration
| MMAD
| GSD
| Cumulative mass of particles (approximate values) less than | |
< 1 µm | < 4 µm | ||||
1st | 5.20 mg/L air | 9.124 µm | 5.443 | 10% | 31% |
2nd | 2.06 mg/L air | 9.768 µm | 2.057 | 0.08% | 11% |
Limit study test results summary
Nominal concentration | Gravimetric (actual) concentration and standard deviation | Mass median aerodynamic diameter (MMAD) | Geometric standard deviation (GSD) | Relation of actual to nominal concentration |
[mg/L air] | [mg/L air] | [µm] |
|
|
49.88# | 5.02 ± 0.02 | 9.205 | 4.913 | 0.10 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- > 5.02
- Quality of whole database:
- The quality of the database is high as a guideline/GLP study is available. (OECD 403/GLP)
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Acute oral toxicity
There is one QSAR report for 3-methylstyrene (CAS No. 100-80-1), one in vivo study in rats for Vinyltoluene (CAS No. 25013-15-4) and one in vivo study in rats for 4-Methylstyrene (CAS No. 622-97-9) available. The QSAR report was selected as the key study as the results were derived from a valid QSAR model and fell into its' applicability domain, with adequate and reliable documentation.
QSAR data
The predicted LD50 is 2321.58 mg/kg based on Consensus, which can be concluded as not classified for acute oral toxicity. The results of the model can be considered reliable in terms of numerical value because the closest neighbours in the test set and training set predicted accurately and both MAE of similar compounds in the test/training set lower than the error observed for the whole dataset. Although the predicted value of the most similar chemical CAS No. 622- 97-9 is slightly lower than experiment value, the difference ≤0.5, which is acceptable.
In vivo data
In an acute oral toxicity test (no guideline/EPA), 42 male Wistar rats were administered Vinyltoluene (98%; combined 55%-70% meta-isomer and 30%-45% para-isomer), either as the undiluted material or as an olive-oil or corn-oil solution emulsified with a 5-10% aqueous solution of acacia (gum arabic) by oral gavage. All the surviving rats were observed until recovery was assured (usually about two weeks). Several experimental details (i.e., doses used, number of animals per dose, statistical methodology, detailed sublethal observations, etc.) were not reported in the study. When the rats were autopsied, slight liver changes and, in some instances, some kidney involvement of questionable significance was observed. The approximate LD50 in male rats is 4.0 g/kg.
In an acute oral toxicity test (no guideline/ChemIDPlus), rats were administered 4-Methylstyrene (CAS No. 622-97-9) orally. No further details were provided. Behavioral tremors, respiratory depression and unspecified gastrointestinal changes were noted. The LD50 in rats of 4-Methylstyrene (CAS No. 622-97-9) is 2255 mg/kg.
Based on the results of the QSAR report and 2 in vivo studies, the LD50 is >2000 mg/kg bw.
Acute inhalation toxicity
There is one acute inhalation toxicity study in the rat available.
In an acute inhalation toxicity study (OECD 403/GLP), a group of young adult Crl: CD(SD) rats (3/sex) were exposed to a test atmosphere of Vinyltoluene (99.66%; 3-Vinyltoluene CAS No. 100-80-1: 64.3 %; 4-Vinyltoluene CAS No. 622-97-9: 35.7 %) in air (aerosol) for 4 hours (nose only) at the target concentration of 5 mg/L air (limit test). Animals were then observed for 14 days.
The determination of the aerosol particle distribution did not reveal the range for MMAD (1 - 4 µm) and GSD (1.5 - 3.0) as recommended in the guideline. The feasibility tests revealed that the MMAD at a concentration of 2 mg/L air (9.768 µm) was even slightly worse compared to a concentration at 5 mg/L air (9.124 µm).The cumulative mass of particles less than 4 µm was approximately 31% at a concentration at 5 mg/L air and only 11% at a concentration at 2 mg/L air. Hence, the use of 5 mg/L air is from a toxicological point of view more suitable than employing 2 mg/L air, as at a concentration of 5 mg/L air the absolute concentration of smaller particles reaching the alveoli is considered to be larger than at 2 mg/L air. The gravimetric (actual) concentration in the limit test was 5.02 ± 0.02 mg/L air. The mean MMAD and GSD were 9.205 μm and 4.913, respectively.
The test item led to mortality/morbidity in only 1 of the 6 animals. One female rat revealed a pronounced sedation until 60 minutes p.a. and was sacrificed prematurely 2 hours after end of exposure due to animal welfare reasons. Systemic toxicity was noted in in form of reduced motility, ataxia, tremor, a reduced respiratory rate, tonic and clonic convulsions, and/or lacrimation immediately after end of exposure up to 3 hours after end of exposure in all 3 of 3 male and up to 3 of 3 female animals. Pilo-erection was noted up to 48 hours after end of exposure. The body weight did not reveal test item-related changes in any of the rats at the end of the study.The macroscopic examination at necropsy did not reveal any changes. Hence, no histopathological examination was performed. No influence on the lung weights was observed. The LC50 male/female was > 5.02 mg/L air.
Justification for classification or non-classification
Based on the available information in the dossier, the substance Vinyltoluene (CAS No. 25013-15-4) is not classified for acute toxicity or specific target organ toxicity, when the criteria outlined in Annex I of 1272/2008/EC are applied.
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.
