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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Klimisch 2e as the study is well documented, meets generally accepted scientific principles and acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Chronic bioassay of benzyl chloride in F344 rats and (C57BL/6J x BALB/c)F1 mice
Author:
Lijinsky W.
Year:
1986
Bibliographic source:
J. Natl.Cancer Inst., 76: 1231-1236

Materials and methods

Principles of method if other than guideline:
Female and male rats were repeatedly exposed to the test substance by oral gavage in a subchronic test. During the experiment they were weekly weighed and at the end of the experiment they were sacrificed and examined histopathologically.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): benzyl chloride
- Physical state: colorless liquid
- Analytical purity: 97.5–98 %
- Composition of test material, percentage of components: Besides 97.5 - 98% benzylchloride, six or seven minor components (e.g. benzene and toluene) each constituting 0.1% or more
- Other:
Supplier: Fisher Scientific Co., Fairlawn, NJ

No more data available

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
26 weeks
Frequency of treatment:
once daily, 3 times/week
Doses / concentrations
Remarks:
Doses / Concentrations:
15, 30, 62, 125 or 250 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
10 male and 10 female rats/group
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
6.4 mg/kg bw/day (nominal)
Sex:
female
Basis for effect level:
other: corresponds to 15 mg/kg
Dose descriptor:
NOEL
Effect level:
12.9 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: corresponds to 30 mg/kg
Dose descriptor:
LOEL
Effect level:
12.9 mg/kg bw/day (nominal)
Sex:
female
Basis for effect level:
other: corresponds to 30 mg/kg
Dose descriptor:
LOEL
Effect level:
26.6 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: corresponds to 62 mg/kg

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Dose of 30 mg/kg (12.9 mg/kg bw/day)

- a few females had hyperkeratosis of the forestomach.

Dose of 62 mg/kg (26.6 mg/kg bw/day)

- females: only 4 survived to 26 weeks; acute myocardial necrosis in 4 and hyperplasia of the forestomachwas observed

- statistically significant depression of weight gain in males, in females the weight gain depression was smaller

Dose of 125 mg/kg (53.6 mg/kg bw/day)

- all females died within 2 weeks

- all males died within 3 weeks

- cause of death was mainly severe acute and chronic gastritis of the forestomach (often with ulcers). In many cases there was also acute myocardial necrosis and edema of the heart

Dose of 250 mg/kg (107.1 mg/kg bw/day)

- all rats died within 2 weeks

- common cause of death was acute myocardial necrosis and edema of the heart

Applicant's summary and conclusion

Conclusions:
The authors tested the oral toxicity of benzyl chloride by repeatedly exposing female and male rats to the test substance by oral gavage in a subchronic test. In these test conditions the NOEL was 6.4 and 12.9 mg/kg bw/day and the LOEL was 12.9 and 26.6 mg/kg bw/day for females and males respectively.
Executive summary:

The authors tested the oral toxicity of benzyl chloride (CAS n° 100-44-7) by repeatedly exposing female and male F344 rats to the test substance by oral gavage in a subchronic test. The test substance was mixed with corn oil and administered once a day, three times a week for 26 weeks.Ten rats/sex were exposed to 15, 30, 62, 125 or 250 mg/kg and a control group was included. During the experiment the rats were weighed and at the end of the experiment tha animals were sacrificed and examined histopathologically.

In these test conditions, a few females exposed to 30 mg/kg (12.9 mg/kg bw/day) had hyperkeratosis of the forestomach. At a dose of 62 mg/kg (26.6 mg/kg bw/day) only four females survived till the end of the experiment (26 weeks). Furthermore acute myocardial necrosis was observed in 4 female rats and hyperplasia of the forestomach was also noted. Also at 62 mg/kg depression of weight gain was seen in females and males, but only for males this decrease in weight gain was statistically significant. Exposure to 125 mg/kg (53.6 mg/kg bw/day) led to death within 2 weeks for all females and 3 weeks for all males. The cause of death was mainly severe acute and chronic gastritis of the forestomach (often with ulcers) and in many cases there was also acute myocardial necrosis and edema of the heart. Finally after exposure to 250 mg/kg (107.1 mg/kg bw/day) all rats died within 2 weeks and the most common cause of death was acute myocardial necrosis and edema of the heart.

Finally, in the test conditions , the aurhors established the NOEL was 6.4 and 12.9 mg/kg bw/day and the LOEL was 12.9 and 26.6 mg/kg bw/day for female and male rats respectively.

No data is available on the GLP status of the study. Although some details of the study are lacking, the study itself is well conducted, well documented, meets generally accepted scientific principles and acceptable for assessment. Therefore we consider it reliable with restrictions, Klimisch 2e.