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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Each animal received a single dose of test chemical in distilled water. Animals were sacrificed 4 hours after treatment. Animals were sacrificed, and cell pellets of liver, intestine and stomach were lysed for 1 hour. Solutions were neutralized, and sonicated. Single and double stranded DNA repair were separated on a hydroxylapatite column at 60°C. Hoechst Dye 33258 was added and the amount of DNA in each fraction was determined fluorimetrically. The fraction of double stranded (ds) DNA remaining after alkaline unwinding in the sample is calculated by dividing the amount of ds DNA by the total (ss + ds) DNA.
GLP compliance:
not specified
Type of assay:
other: DNA alkaline unwinding assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No further data

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Wilmington, MA, USA
- Age at study initiation: no data
- Weight at study initiation: 30-35 g prior to acclimatization for 2 weeks.
- Assigned to test groups randomly: [no/yes, under following basis: ] no data
- Fasting period before study: no fasting period
- Housing: no data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 ± 2 °C
- Humidity (%): 40-60%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: no data

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
Distilled water.
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: test chemical was dissolved in distilled water
Duration of treatment / exposure:
Animals were sacrificed 4 hours after treatment
Frequency of treatment:
Once
Post exposure period:
4 hours
Doses / concentrationsopen allclose all
Dose / conc.:
1 other: mmol/kg
Dose / conc.:
10 other: mmol/kg
No. of animals per sex per dose:
2 animals per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
- Methylmethanesulfonate
- Route of administration: oral
- Doses / concentrations: 1 mmol/kg

Examinations

Tissues and cell types examined:
liver, stomach, duodenum
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: doses up to 1/4 to 1/3 of the LD50

METHOD OF ANALYSIS: Cell pellets of liver, intestine and stomach were lysed for 1 hour. Solutions were neutralized, and sonicated. Singel and double stranded DNA repair were separated on a hydroxylapatite column at 60°C. Hoechst Dye 33258 was added and the amount of DNA in each fraction was determined fluorimetrically. The fraction of double stranded (ds) DNA remaining after alkaline unwinding in the sample is calculated by dividing the amount of ds DNA by the total (ss + ds) DNA.
Evaluation criteria:
No data
Statistics:
Dunnett's test for multiple comparison of treatment means with a control mean. Level of significance was set at < 0.05

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
RESULTS OF STUDY
No significant increase in DNA strand breaks following exposure to 1 or 10 mmol/kg MCA

Applicant's summary and conclusion

Conclusions:
MCA did not induce DNA strand breaks following oral exposure to male B6C3F1 mice and is considered not mutagenic in this in vivo study.