Registration Dossier

Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1972
Report Date:
1972

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
no
Type of assay:
other: cytogenicity study: bone marrow chromosome aberration

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on species / strain selection:
flow laboratories random-bred, closed colony, Sprangue-Dawley CD strain rats (ten to twelve weeks old, 280 - 350 g)
Sex:
not specified
Details on test animals and environmental conditions:
Husbandry
Each animal room utilized in the study contained only one species. Rats were housed one to five to a cage as prescribed in each protocol. Animals were identified by ear punch. Sanitary cages and bedding were used, and changed two times per week, at which time water containers were cleaned, sanitized and filled. Once a week, cages were repositioned on racks; racks were repositioned within rooms monthly. Personnel handling animals or working with animal facilities wore head covering and face masks as well as suitable garments. Individuals with respiratory or other overt infections were excluded from the animal facilities.

Administration / exposure

Route of administration:
other: intubation or by mixing the compound in the feed
Details on exposure:
Preparation of Diet
A commercial 4%.fat diet was fed to all animals. Periodic tests to verify the absence of coliforms, Salmonella and Pseudomonas sp. were performed.

Dosage Determination
1. High Levels were prepared from information supplied by the sponsor.
2. The Usage Level was 1/10 of the Intermediate Level.
3. The Intermediate Level was 1/10 of the High Level.
4. Subacute Doses were identical to those used in the acute studies unless contraindicated.
C. Mutagenicity Testing Protocols 1. Cytogenetic Studies
Ten to twelve week old male, albino rats obtained from a closed colony (random-bred) were used, as illustrated in the following protocol:

Number of animals used
Subacute Study
Treatment Time Killed after Administration
48 hours 5 days
High Level 5
Medium Level 5
Low Level 5
Positive Control 5
Negative Control 3

Dosage: 1x/day x 5 days
Doses / concentrationsopen allclose all
Dose / conc.:
0.63 mg/kg bw/day (nominal)
Remarks:
Low dose level (dose contained in 1 mL)
The solvent employed was 0.5 % methylcellulose. The solution was prepared on a volume/volume basis.
Dose / conc.:
6.3 mg/kg bw/day (nominal)
Remarks:
Medium dose level (dose contained in 1 mL)
The solvent employed was 0.5 % methylcellulose. The solution was prepared on a volume/volume basis.
Dose / conc.:
63 mg/kg bw/day (nominal)
Remarks:
High dose level (dose contained in 1 mL)
The solvent employed was 0.5 % methylcellulose. The solution was prepared on a volume/volume basis.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
triethylene melamine (dose 0.3 mg/kg bw/day contained in 1 mL)
The solvent employed was 0.5 % methylcellulose. The solution was prepared on a volume/volume basis.

Results and discussion

Any other information on results incl. tables

Cytogenetics

This compound produced no detectable significant aberrations of the bone marrow metaphase chromosomes of rats when administered orally at the dosage levels employed in this study.

Toxicity

No abnormal signs or pathology were noted in the animals used at the dose levels employed.

Test

Cytogenetics—The negative control group contained 2% breaks and the positive controls showed the expected severe damage. The intermediate and high (LD5) groups each contained 3% cells with breaks. This was not considered significant and is within historical negative control values.

Metaphase summary sheet

Compound Dosage*
(mg/kg)
No. Of
Animals
No. of
Cells
Mitotic Index % % Cells
with Breaks
% Cells with
Reunions
% Cells with more than 1 type of aber. % Cells with Aber.
Negative control methocel 3 150 9 2 0 0 2
Low level 0.63 5 250 9 0 0 0 0
Intermediate level 6.3 5 250 6 3 0 0 0
High level 63 5 250 7 3 0 0 3
Positive control (TEM**) 0.3 5 250 3 28 9 3 39
* Dosage 1x/day x 5 days
** TEM (Triethyl melamine) administered in an acute dose only one time. Animals killed 48 hours after administration of compound.

Applicant's summary and conclusion

Conclusions:
The compound vinylbenzyl chloride produced no detectable significant aberrations of the bone marrow metaphase chromosomes of rats when administered orally at the dosage levels employed in this study (0, 0.63, 6.3, and 63 mg/kg bw/day administered for 5 consecutive days).
Executive summary:

In a cytogenetics study in rats, doses of 0, 0.63, 6.3, and 63 mg/kg bw/day of vinylbenzyl chloride were orally administered on 5 consecutive days (5 animals per treatment group, 3 animals in the negative control group, 5 animals in the positive control group administered triethylene melamine). No abnormal signs or pathology were noted in the animals at the dose levels employed, and no detectable significant aberrations of the bone marrow metaphase chromosomes of rats were observed.

Cytogenetics of the bone marrow: The negative control group contained 2% breaks and the positive controls showed the expected severe damage. The intermediate and high dose groups each contained 3% cells with breaks. This was not considered significant and is within historical negative control values.