Registration Dossier

Administrative data

Endpoint:
carcinogenicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is sufficiently documented, acceptable for assessment and conducted with generally accepted scientific principles. Therefore, this study should be considered as reliable with restrictions.

Data source

Reference
Reference Type:
publication
Title:
Carcinogenicity of benzyl chloride, benzal chloride, benzotrichloride and benzoyl chloride in mice by skin application
Author:
Fukuda K., Matsushita H., Sakabe H. and Takemoto K.
Year:
1981
Bibliographic source:
GANN, 72, 655-664.

Materials and methods

Principles of method if other than guideline:
The authors conducted a repeated dose toxicity tests (42 and 50 weeks period) on female mice by painting benzal chloride on skin. cf examinations for full details
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): BAC, benzal chloride
- Analytical purity: reagent grade commercial obtained from Wako pure chemicals industries Co.
No further data

Test animals

Species:
mouse
Strain:
ICR
Sex:
female

Administration / exposure

Route of administration:
dermal
Vehicle:
other: benzene
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
- Experiment II: about ten months (9.8 months, 42 weeks)
- Experiment III: about twelve months (11.7 months, 50 weeks)
Frequency of treatment:
- Experiment II: 3/w for the initial 4 weeks, and thereafter 2/w until the end of the experiment
- Experiment III: twice a week during 12 months
Post exposure period:
- Experiment II: No post observation
- Experiment III: 7 months
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2.3 µL
Basis:
analytical conc.
pipette measured
Remarks:
Doses / Concentrations:
10 µL
Basis:
analytical conc.
pipette measured
No. of animals per sex per dose:
- Experiment II: 10 female exposed to 10 µL 3/w for the initial 4 weeks, and thereafter 2/w until the end of the experiment
- Experiment III: 19 females exposed to 2.3 µL twice a week during 12 months
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Remarks:
Impossible due to study design
Sex:
female
Remarks on result:
not determinable
Remarks:
no NOAEL identified. Effect type:carcinogenicity (migrated information)

Any other information on results incl. tables

During a few minutes after dermal painting of mice a marked irritation of the eyes, the skin and the respiratory system as well as elevated motor activities were seen.

At the painted area first erythema and swelling were noted later alopecia, induration, marked keratinization, ulcers and/or necrosis of the epidermis were observed. The lesions were rather severe.

Experiment II:

The dose represented a total of 1100 mg over the exposure period (294 days; around 3.7 mg/day). Mortality at termination was 0 and 0 for the control and the tested-dose groups, respectively. The number of mice with tumours was 0/10 and 4/10 in the control and tested-dose groups, respectively.

Experiment III:

The total dose was approximately 288 mg over the exposure period (351 days; 0.82 mg/day). Mortality at termination was 20% in the controls compared with 74% in the treated group. In the control group, 2/20 mice had lung adenomas while in the treated group, 11/19 had skin carcinoma and 5/19 had lung adenoma/carcinoma. One mouse was observed with other tumors in the lips (two squamous cell carcinomas) and in the forestomach (squamous cell carcinoma). These carcinomas were attributed to the licking.

Applicant's summary and conclusion

Conclusions:
In the test conditions, the authors showed that benzal chloride painted regularly at low level (0.82 mg/day) on the clipped back of female mice induced significantly more skin carcinomas than in the control (pure benzene) over a 12 month exposure period.
Executive summary:

The authors tested the carcinogenicity of benzal chloride (CAS n° 98 -87 -3 ), besides multiple chlorinated compounds, on clipped skin of female IRC mice (seven weeks old) in a serie of experiment.

They created in the longest subset of expreriment, two groups each consisting of 19 (tested dose) or 20 female mice (control) which were given skin applications of 25 µL of benzene (for vehicle controls) or 25 ul of a 9.2% solution of benzal chloride in benzene twice a week for 50 wk (total dose, about 288 mg/animal). All mice were killed at week 82 and checked besides mortality along the test, on tumors development and histopathological changes.

Furthermore, no skin tumor was observed in any control. Of the 19 benzal chloride treated mice, 14 (74%) had died by the end of the experiment; 12 (63%) developed tumors: 9 with squamous cell carcinomas of the skin (p < 0.01), 2 with skin fibrosarcoma, and 1 with a lymphoma; lung adenomas were reported in 5 treated mice and 2 controls.

At this level of information, no effect level coud have been derivated as the study design was not intentionnaly build for this. Besides, the number of tested animals was not sufficient to reach a reliable level and to be representative.

However the general scientific principle of the test is good and the study is sufficiently described. This study should therefore be considered as reliable with restrictions and the document acceptable for assessment.