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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
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:
publication
Title:
Mutagenic activity of 41 compounds in the in vivo micronucleus assay
Author:
Salamone, M.F., Heddle, H.A., and Katz, M.
Year:
1981
Bibliographic source:
In Progress In MutationResearch: Evaluation of Short-Term Tests for Carcinogens (F.J. de Serres and J. Ashby, Eds.),Vol. I, pp. 686-697. Elsevier North Holland, NewYork

Materials and methods

Principles of method if other than guideline:
This investigation used a new protocol that incorporates multiple samples and consists of two phases In the first phase, mice were injected intraperitoneally with test agent at 0 and 24 hr, and samples were taken at 48, 72, and 96 hr. Each treatment consisted of a dose equal to 80% of the 7-day LD50. If there was a significant increase in the frequency of micronuclei at any sample time, then the treatment was repeated and animals sampled at the appropriate time or a graded series of doses were tested at the appropriate sample time. In either case, the agent was classified as clastogenic if there was a confirmation of the initial positive response, no further testing was performed. If in phase 1 or in the confirmation test no increase in the micronucleus frequency was detected, then a single treatment of either 50% or at both 80% and 40% of the 7-day LD50 was given and samples were taken at 30, 48, and 72 hr (phase 2). Where the response was negative for both phases, the agent was classified as nonclastogenic. However, when an increase in the frequency of micronuclei was noted in phase 2, a confirmation test was then performed. In general, when the results from phases 1 and 2 did not agree, a third test was used to reach a decision.
GLP compliance:
not specified
Type of assay:
mammalian erythrocyte micronucleus test

Test material

Constituent 1
Chemical structure
Reference substance name:
γ-butyrolactone
EC Number:
202-509-5
EC Name:
γ-butyrolactone
Cas Number:
96-48-0
Molecular formula:
C4H6O2
IUPAC Name:
dihydrofuran-2(3H)-one

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals or test system and environmental conditions:
B6C3Fl hybrid mice were purchased from Biobreeders Laboratory, Ottawa, Ontario.

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: no data
Frequency of treatment:
Phase 1: mice were injected intraperitoneally at 0 and 24 hr, and samples were taken at 48, 72, and 96 hr.
Phase 2: single treatment
Post exposure period:
Phase 1: samples were taken at 48, 72, and 96 hr after the last treatment
Phase 2: 30, 48, and 72 hr after the treatment
Doses / concentrationsopen allclose all
Dose / conc.:
1.4 other: mL/kg
Remarks:
Phase 1: 2 doses of 80% of the 7-day LD50 (0.875 ml/kg)
Dose / conc.:
0.875 other: mL/kg
Remarks:
Phase 2: 1 dose at 100% of the 7-day LD50 (0.875 mL/kg)
Dose / conc.:
0.438 other: mL/kg
Remarks:
Phase 2: 1 dose at 50% of the 7-day LD50 (0.875 mL/kg)
No. of animals per sex per dose:
5 males per group
Control animals:
not specified
Positive control(s):
Not shown. This was part of a study of the protocol on 41 coded compounds, many of which were known clastogens and were identified as positive by this protocol.

Results and discussion

Test results
Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified

Any other information on results incl. tables

For this material Phase 1 and Phase 2 were negative giving the following number of micronuclei per 500 PCE at the indicated sampling times after 2 doses of 80% of the 7-day LD50:

Time # PCE/Mouse (5 per group)

48 hours 0,0,0,1,1

72 hours 0,0,0,1,1

96 hours 0,0,0,1,0

Phase 2: 1 dose at 100% of the 7-day LD50

Time # PCE/Mouse (5 per group)

36 hours 0,0,0,0,0

48 hours 0,0,0,0,0

72 hours 0,0,0,1,0

Phase 2: 1 dose at 50% of the 7-day LD50

Time # PCE/Mouse (4 per group)

36 hours 0,0,0,0

48 hours 0,0,0,0

72 hours 0,0,0,0

Applicant's summary and conclusion

Conclusions:
negative