Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
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 lack of effects of pretreatment with phenobarbitol and chlorpromazine on the acute toxicity of benzene in rats
Author:
Drew RT and Fouts JR.
Year:
1974
Bibliographic source:
Toxic. Appl. Pharmacol. 27, 183-193

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
only females, group size of 10 or 12
GLP compliance:
not specified
Test type:
other:
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Reagent grade thiophene-free benzene containing no contaminants above a concentration of 0.05%
- Supplier: J T Baker Chemical Co.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 150-225 g
- Diet: NIH-D & G or Wayne Lab-Blox ad libitum except during exposure
- Water: ad libitum except during exposure

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 h dark / 12 h light
- No further details reported

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
Single 4 h inhalation exposures were performed in a chamber. Vapours generated by passing air through 2 fritted bubblers in series, each containing benzene. First bubbler maintained at approx. 35°C assuring that air emerging from second bubbler was saturated with benzene. The saturated air was diluted with filtered compressed air to desired concentration. Chamber concentrations of benzene were monitored at 30 minute intervals on a spectrophotometer.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
6 exposure levels ranging from 11500-15500 ppm (exact levels not reported)
No. of animals per sex per dose:
10 or 12 female
Control animals:
no

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LC50
Effect level:
13 700 ppm
95% CL:
13 050 - 14 380
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
43 767 mg/m³ air (nominal)
95% CL:
41 690 - 45 939
Exp. duration:
4 h
Mortality:
Animals which died as a result of exposure to benzene usually died during the exposure or in the first 24 h post-exposure. Death appeared to be caused by a depression of the central nervous system. These animals all had higher weights for both lung and liver.
Other findings:
Lung and liver congestion, defined as an increase in the number of red blood cells, and increases in the number of vacuolated hepatocytes seen in the livers of those animals which died from inhalation of benzene, were the principal observations noted histopathologically.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 for benzene to female rats was 13700 ppm (43767 mg/m3; 43.7 mg/L) with a range of 13050-14380 ppm (41690-45939 mg/m3).
Executive summary:

The acute inhalation LC50 of benzene was determined in groups of 10 or 12 female rats to be 13700 ppm (43767 mg/m3; 43.7mg/L) with a range of 13050-14380 ppm (41690-45939 mg/m3). Death appeared to be caused by a depression of the CNS. These animals had increased lung and liver weights, lung and liver congestion and an increased number of vacuolated hepatocytes in the liver.

Benzene is of low acute inhalation toxicity and does not warrant classification under Dir 67/548/EEC.