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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline, non-GLP, animal experimental study, published in peer-reviewed literature. Pre-dates implementation of GLP and guideline but otherwise acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
The joint toxic action of perchloroethylene with benzene or toluene in rats
Author:
Withey RJ and Hall JW
Year:
1975
Bibliographic source:
Toxicology 4, 5-15

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
only male rats used
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Toluene
EC Number:
203-625-9
EC Name:
Toluene
Cas Number:
108-88-3
Molecular formula:
C7H8
IUPAC Name:
toluene
Details on test material:
- purity not stated

Test animals

Species:
rat
Strain:
other: Sprague-Dawley Cobb
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Canadian Breeding Farms, St. Constante, Quebec, Canada
- Weight at study initiation: 150-200 g
- Fasting period before study: overnight prior to dosing
- Housing: individually
- Diet: rat pelleted diet ad libitum
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Dose levels selected based on the results of a pilot study

Doses:
5 dose levels; 4000, 4560, 5200, 5930, or 6760 mg/kg
No. of animals per sex per dose:
20 males
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: observed three times daily, weighed prior to the day of dosing
- Necropsy of survivors performed: yes
Statistics:
LD50's were estimated by the method of probit analysis. The analysis included a goodness of fit test to ensure that the probit model was applicable.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
5 580 mg/kg bw
95% CL:
5 300 - 5 910
Remarks on result:
other: death within 36 hours of dosing and neurotoxic effects at high doses
Mortality:
The majority of deaths occurred 24-36 hours after dosing
Clinical signs:
Rats dosed at high levels with toluene exhibited hind-limb paralysis and petechial bleeding, especially from the urinary tract, eyes and nose
Body weight:
No data
Gross pathology:
Epithelial cells of the stomach lining were stripped and mild acute gastritis was observed in the glandular portion

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of toluene, calculated by probit analysis, was 5580 mg/kg to male rats.
Executive summary:

The acute oral LD50 was determined to be >5000 mg/kg using groups of 20 males rats. Toluene is of low oral toxicity and does not warrant classification under Dir 67/548/EEC or GHS.