Toluene

Acute Toxicity: oral

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

Test material information

Constituent 1

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:

other: Rats dosed at high levels with toluene exhibited hind-limb paralysis and petechial bleeding, especially from the urinary tract, eyes and nose

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.