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Toxicological information

Genetic toxicity: in vivo

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Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-09-22 to 1992-11-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is rated "reliable with restrictions" because though this study did not specify the use of GLP guidance it was conducted in close accordance to OECD TG 474
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-09-22 to 1992-11-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is rated "reliable with restrictions" because though this study did not specify the use of GLP guidance it was conducted in close accordance to OECD TG 474
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
no
Type of assay:
micronucleus assay
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Route of administration:
inhalation: vapour
Vehicle:
- Vehicle(s)/solvent(s) used: Air
- Concentration of test material in vehicle: 1000 ppm
Duration of treatment / exposure:
6 hours/day
Frequency of treatment:
Daily for 10 consecutive days
Post exposure period:
Samples collected 24 hours post last exposure
Remarks:
Doses / Concentrations:
1000 ppm
Basis:

No. of animals per sex per dose:
5/sex/dose group
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide
- Justification for choice of positive control(s): Not provided
- Route of administration: Oral gavage
- Doses / concentrations: 40 mg/kg
Tissues and cell types examined:
Bone marrow suspended in fetal bovine serum; 1000 polychromatic erythrocytes (PCE) were examined from each exposed animal for the presence of micronuclei. In addition, the ratio of PCEs to NCEs were determined for each animal by counting 1000 erythrocytes (PCEs and NCEs)
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
MRD 92-321 did not induce a statistically significant decrease in the mean percent of polychromatic erythrocytes which is a measure of bone marrow toxicity. Hence, the test chemical was not toxic to the B6C3F1 mouse bone marrow.
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Conclusions:
negative

MRD 92-321 did not induce a statistically significant decrease in the mean percent of polychromatic erythrocytes which is a measure of bone marrow toxicity. Hence, the test chemical was not toxic to the B6C3F1 mouse bone marrow under the conditions of the test. The test material also did not induce a statistically significant increase in the mean number of micronucleated polychromatic erythrocytes. Based on these results, the test material is not clastogenic to the bone marrow of the B6C3F1 mouse.
Executive summary:

In an in-vivo micronucleus assay, five male and five female B6C3F1 mice were exposed nose only for six hours/day for ten consecutive days to 1000 ppm of MRD 92-321 (C6 alkene) in air. The positive control, cyclophosphamide in water, was administered via oral gavage at a dose of 40 mg/kg, while air served as the negative control. Bone marrow samples were collected at approximately 24 hours after the last exposure and evaluated for micronucleus formation.

 

MRD 92-321 did not induce a statistically significant decrease in the mean percent of polychromatic erythrocytes which is a measure of bone marrow toxicity. The test material also did not induce a statistically significant increase in the mean number of micronucleated polychromatic erythrocytes. The positive and negative control gave appropriate results. Based on these results, the test material is not clastogenic to the bone marrow of the B6C3F1 mouse.

 

This study received a Klimisch score of 2 and is classified as “reliable with restrictions” because though this study did not specify the use of GLP guidance it was conducted in close accordance to OECD TG 474.

 

[This study was selected as a supporting study because …………………]

 

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MRD 92-321 (C6 Alkene; hexene)
- Substance type: Alkenes, C6
- Physical state: Colourless liquid

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: vapour
Vehicle:
- Vehicle(s)/solvent(s) used: Air
- Concentration of test material in vehicle: 1000 ppm
Duration of treatment / exposure:
6 hours/day
Frequency of treatment:
Daily for 10 consecutive days
Post exposure period:
Samples collected 24 hours post last exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 ppm
Basis:

No. of animals per sex per dose:
5/sex/dose group
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide
- Justification for choice of positive control(s): Not provided
- Route of administration: Oral gavage
- Doses / concentrations: 40 mg/kg

Examinations

Tissues and cell types examined:
Bone marrow suspended in fetal bovine serum; 1000 polychromatic erythrocytes (PCE) were examined from each exposed animal for the presence of micronuclei. In addition, the ratio of PCEs to NCEs were determined for each animal by counting 1000 erythrocytes (PCEs and NCEs)

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
MRD 92-321 did not induce a statistically significant decrease in the mean percent of polychromatic erythrocytes which is a measure of bone marrow toxicity. Hence, the test chemical was not toxic to the B6C3F1 mouse bone marrow.
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
negative

MRD 92-321 did not induce a statistically significant decrease in the mean percent of polychromatic erythrocytes which is a measure of bone marrow toxicity. Hence, the test chemical was not toxic to the B6C3F1 mouse bone marrow under the conditions of the test. The test material also did not induce a statistically significant increase in the mean number of micronucleated polychromatic erythrocytes. Based on these results, the test material is not clastogenic to the bone marrow of the B6C3F1 mouse.
Executive summary:

In an in-vivo micronucleus assay, five male and five female B6C3F1 mice were exposed nose only for six hours/day for ten consecutive days to 1000 ppm of MRD 92-321 (C6 alkene) in air. The positive control, cyclophosphamide in water, was administered via oral gavage at a dose of 40 mg/kg, while air served as the negative control. Bone marrow samples were collected at approximately 24 hours after the last exposure and evaluated for micronucleus formation.

 

MRD 92-321 did not induce a statistically significant decrease in the mean percent of polychromatic erythrocytes which is a measure of bone marrow toxicity. The test material also did not induce a statistically significant increase in the mean number of micronucleated polychromatic erythrocytes. The positive and negative control gave appropriate results. Based on these results, the test material is not clastogenic to the bone marrow of the B6C3F1 mouse.

 

This study received a Klimisch score of 2 and is classified as “reliable with restrictions” because though this study did not specify the use of GLP guidance it was conducted in close accordance to OECD TG 474.

 

[This study was selected as a supporting study because …………………]