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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is well documented, meets generally accepted scientific principles and acceptable for assessment, thus klimisch 2e

Data source

Reference
Reference Type:
publication
Title:
Histopathological changes in the respiratory tract of mice exposed to ten families of airborne chemicals
Author:
Zissu D.
Year:
1995
Bibliographic source:
Journal of Applied Toxicology, 15(3): 207-213

Materials and methods

Principles of method if other than guideline:
Identify and compare the histological changes induced in the respiratory tract of Swiss mice exposed to repeated inhalation
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
α-chlorotoluene
EC Number:
202-853-6
EC Name:
α-chlorotoluene
Cas Number:
100-44-7
Molecular formula:
C7H7Cl
IUPAC Name:
(chloromethyl)benzene
Constituent 2
Reference substance name:
chloromethylbenzene
IUPAC Name:
chloromethylbenzene
Details on test material:
- Name of test material (as cited in study report): benzyl chloride
- Analytical purity: 99%
- Other:
Supplier: Merck Schuchard (Darmstadt, Germany)

No more data available

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4, 9, 14 days
Frequency of treatment:
4-day exposure: 6 hours per day, four consecutive days
9-day exposure: 6 hours per day; five consecutive days for the first week and four consecutive days for the second week
14-day exposure: 6 hours per day; five consecutive days for each of the first 2 weeks and four consecutive for the third week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
22 ppm (107 mg/m³)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
46 ppm (224 mg/m³)
Basis:
analytical conc.
No. of animals per sex per dose:
ten mice/dose (5 mice/dose as control)
Control animals:
yes, concurrent no treatment

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
22 ppm
Sex:
male
Basis for effect level:
other: 107 mg/m³
Dose descriptor:
LOEL
Effect level:
46 ppm
Sex:
male
Basis for effect level:
other: 224 mg/m³

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Clinical observations:

No mortality in treated and control groups during experiment

Histology of nasal passages:

Control: No histological disease, no neutrophils and no other inflammatory exudate

Treated animals: respiratory and olfactory epithelia lesion was observed at 46 ppm. Severity of lesions was severe to very severe but no relation was observed to exposure duration.

Trachea and lungs:

No injuries

Applicant's summary and conclusion

Conclusions:
The authors tested the repeated dose inhalation toxicity of benzyl chloride by identifying and comparing the histological changes induced in the respiratory tract of Swiss male mice. Neither mortality nor injuries in the trachea and lungs were observed in all treated mice. At the low dose exposure (22 ppm) no effects were observed caused by the treatment. In mice exposed to the high dose respiratory and olfactory epithelia lesions were observed. Although these lesions were severe to very severe no relation to the exposure duration was observed.
Executive summary:

The authors tested the repeated dose inhalation toxicity of benzyl chloride (CAS n° 100 -44 -7) by identifying and comparing the histological changes induced in the respiratory tract of Swiss male mice. Three subacute repeated dose tests with different exposure duration were performed and in each one animals were exposed to the test substance 6 hours per day. The following exposure durations were used: (1) four consecutive days of exposure, (2) exposing animals five consecutive days in the first week and four consecutive days in the second week and (3) exposing animals five consecutive days in each of the first 2 weeks and four consecutive days in the third week. For each of these exposure scenarios two concentrations were tested (i.e. 22 and 46 ppm) and 10 mice were exposed per dose. Per dose tested a control group of five mice was included.

Neither mortality nor injuries in the trachea and lungs were observed in all treated as well as the control mice. Furthermore no histological disease, no neutrophils and no other inflammatory exudate was noted in the nasal passages of the control mice. At the low dose exposure of 22 ppm no effects were observed caused by the treatment, thus the NOEL is 22 ppm. The LOEL is 46 ppm and mice exposed to this dosis exhibited respiratory and olfactory epithelia lesions. Although these lesions were severe to very severe no relation to the exposure duration was observed.

The GLP status of the study is unknown, but it is sufficiently described, based on generally well accepted scientific principles and acceptable for assessment. Therefore, this study should be considered reliable with restrictions, Klimisch 2e.

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