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Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information
The study (Little, 1990) about genetic toxicity in vitro is available which gave negative result. The study (Little, 1990) about genetic toxicity in vivo is available which gave ambiguous result.
Link to relevant study records
Reference
Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11/1989-03/1990
Reliability:
2 (reliable with restrictions)
Qualifier:
no guideline followed
Principles of method if other than guideline:
Guideline followed not specified. In-vivo Chromosome aberration study in bone marrow
GLP compliance:
yes
Type of assay:
chromosome aberration assay
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Taconic(Germantown, NY)
- Age at study initiation:7weeks
- Weight at study initiation:
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study:
- Housing: in suspended stainless steel cages with Easi-litter bedding
- Diet (e.g. ad libitum): Agway Standard Rodent Chow ad libitum
- Water (e.g. ad libitum):Cambridge City tap water ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 to 30°C
- Humidity (%):
- Air changes (per hr):28 to 60%
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
water
Duration of treatment / exposure:
Single OG dosage. Sacrifice after 6, 18 or 24 hours.
Remarks:
Doses / Concentrations:
150, 500, 1500 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
18 rats/sex/group received at 150,500,1500mg/kg
5 rats/sex received Base at 3000mg/kg toxic dose, so not analysed
18 rats/sex received the vehicle (control)
6 rats/sex received 30mg/kg of cyclophosphamide (positive control)
Control animals:
yes, concurrent vehicle
Sex:
male/female
Genotoxicity:
ambiguous
Toxicity:
yes
Remarks:
4/6 females died at 1500mg/kg at 6hrs; 1/6 females died at 1500mg/kg at 24hrs
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Rats dosed at 3000 mg/kg were not analyzed due to toxicity. In females, 4/6 rats dosed at 1500 mg/kg (6-hour timepoint) and 1/6 rats dosed at 1500 mg/kg (24-hour timepoint) died prior to the scheduled sacrifice. No deaths occurred in males. An increase in the percent of cells with aberrations was noted in the 1500mg/kg males at the 6-hour sacrifice (4.8% cells with chromosomal aberrations compared to 1.6% for pooled negative controls and 2.4% in the six hour negative control). No increase in the percent of cells with aberrations or the number of aberrations per cell was seen at the 6-hour timepoint in the males treated with 150 or 500 mg/kg, in males at the 18 and 24 hour timepoints at any dose, or in any females. The positive and the negative controls showed the appropriate response indicating the assay was valid.
Conclusions:
Interpretation of results (migrated information): ambiguous
The substance was administered as a single dose by oral gavage to male and female rats at 150, 500, and 1500 mg/kg to evalute its clastogenic potential. An increase in the percentage of cells with aberrations was seen in the 1500 mg/kg male group sacrificed 6 hours after treatment (4.8% as compared to 1.6% in the pooled control and 2.4% in concurrent controls); no increase were seen in the other male groups at 6 hours, in any male group at 18 or 24 hours, or in any female group at 6, 18, or 24 hours. This response was considered ambiguous but may indicate that the substance is a potential clastogen in male rats, however, no dose response was observed and no response was observed at 18 or 24 hours or in female rats. The response of the positive and negative controls indicated that assay was valid.

Additional information

Additional information from genetic toxicity in vivo:

The study (Little, 1990) about genetic toxicity in vitro is available which gave negative result. Key study.

The study (Little, 1990) about genetic toxicity in vivo is available which gave ambiguous result. Key study.


Justification for selection of genetic toxicity endpoint
The study in vivo mammalian cells was chosen over that in vitro, as the higher level study.

Justification for classification or non-classification