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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
other information
Study period:
4 October 1996 - 18 February 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997
Reference Type:
publication
Title:
Genotoxicity Tests with|6-Acetyl-1,1,2,4,4,7- hexamethyltetraline and|1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma|--benzopyran.
Author:
Api, A.M., and San, R.H.C.
Year:
1999
Bibliographic source:
Mutation Research, 446: 67-81.

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylindeno[5,6-c]pyran
EC Number:
214-946-9
EC Name:
1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylindeno[5,6-c]pyran
Cas Number:
1222-05-5
Molecular formula:
C18H26O
IUPAC Name:
4,6,6,7,8,8-hexamethyl-1H,3H,4H,6H,7H,8H-indeno[5,6-c]pyran
Test material form:
liquid: viscous

Results and discussion

Test results
Key result
Genotoxicity:
negative
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF MAIN STUDY
-Appropriateness of dose levels and route: The dose level and route seems to be appropriate
-No mortality in mice was seen. Lethargy was observed in all animals on 1500 mg/kg bw, in 4/15 males and 4/15 females on 750 mg/kg, and 1/15 males and 0/15 females on 376 mg/kg bw.
-Reductions of up to 25% in the ratio of polychromatic erythrocytes to total erythrocytes were observed in some of the test item related groups relative to their vehicle controls. The reduction in the bone marrow suggests that there was toxicity and bioavailability of the test article to the bone marrow target tissue.
-The number of micronucleated polychromatic erythrocytes per 1000 polychromatic erythrocytes in the test item treated groups was not statistically increased relative to their respective vehicle control for all dose groups.

Any other information on results incl. tables

Summary of bone marrow micronucleus study using HHCB.











































































































































































































































































































































































































Treatment SexTime (hrs)Micronucleated polychromatic erythrocytes (number/1000 PCEs) ± Stdev
Corn oil         
20 mL/kg bwM241±0.71    
 F240.4±0.55    
HHCB         
376 mg/kg bwM240.6±0.89    
 F240.2±0.45    
750 mg/kg bwM240.2±0.45    
 F 1.2±1.3    
1500 mg/kg bwM240.4±0.55    
 F240.6±0.55    
CP         
60 mg/kg bwM2443.6±9.29    
 F2437.4±15.73    
          
Corn oil         
20 mL/kg bwM480.6±0.89    
 F481±1.22    
376 mg/kg bwM481±1    
 F480.4±0.55    
750 mg/kgM481.6±1.52    
 F480.2±0.45    
1500 mg/kgM481.2±1.1    
 F480.8±0.84    
Corn oil         
20 mL/kg bwM720.6±0.89    
 F720.8±0.84    
376 mg/kg bwM721.2±1.3    
 F721±1    
750 mg/kg bwM721.4±0.55    
 F721.2±1.64    
1500 mg/kg bwM720.6±0.55    
 F721±0.71    

Applicant's summary and conclusion

Conclusions:
The substance is negative in the micronuleus cytogenetic assay (OECD TG 474).
Executive summary:

In the micronucleus test (OECD TG 474, GLP), groups of 5 male (28.1-37.2 g) and 5 female ICR mice (24.5-31.0 g) were dosed with 0, 376, 750, or 1500 mg/kg bw test item (in corn oil - purity >99%) by intraperitoneal injection at a constant volume of 20 ml/kg bw. The high dose was selected to be approximately 70% of the estimated intraperitoneal LD50 based on a preliminary test. The positive control was cyclophosphamide. Bone marrow was harvested at 24, 48 and 72 hr after dosing and examined for micronucleated polychromatic erythrocytes (PCE). No mortality was seen. Lethargy was observed in all animals on 1500 mg/kg bw, in 4/15 males and 4/15 females on 750 mg/kg, and 1/15 males and 0/15 females on 376 mg/kg bw. Moderate reductions (up to 25%) in the ratio of PCE to total erythrocytes were observed in groups on 1500 mg/kg bw after 48 and 72 hrs indicating toxicity and bioavailability to the bone marrow target. The positive control induced a significant increase in micronucleated PCE in both male and female mice at 24 hr (the only harvest time for this group). No significant increase in micronucleated PCE in HHCB-treated groups relative to the respective vehicle control group was observed in male or female mice at 24, 48 or 72 hr after dose administration. Based on this the substance is not cytogenetic in this test.

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