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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Method and results sufficiently described, with significant technical problems

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
GLP compliance:
no
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Supplied by ICI; contained 11 ppm hydroquinone stabilizer.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Unit, Alderley Park, Cheshire
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 150-200 g
- Housing: four/cage
- Diet (e.g. ad libitum): Alderley Park rat cubes
- Water (e.g. ad libitum): unspecified


ENVIRONMENTAL CONDITIONS
- Air changes (per hr): minimum 8
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation
Vehicle:
unchanged
Details on exposure:
whole body
Duration of treatment / exposure:
single treatment: 2 hours
repeated treatment: 5 hours
Frequency of treatment:
repeated treatment: daily for 5 days
Post exposure period:
24 h after the last exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
ca. 0.4, 1.6, 2.8 and 4 mg/L (corresponding to 100, 400, 700, 1000 ppm)
Basis:
nominal conc.
No. of animals per sex per dose:
12 animals in the negative control group; 8 animals in each of the treated and positive control groups.
Control animals:
yes, concurrent no treatment
Positive control(s):
Benzene, 7500 ppm

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
Bone marrow was collected 24 hours after the single two hour exposure and processed for scoring (blind). Categories used during evaluation included Chromatid or chromsome gaps, Chromatid breaks, Fragments, Minutes or Any other complex abnormality.
Statistics:
Proportion of cells with any abnormalities or proportion of cells with any abnormalities other than gaps: Analysis of Variance after transformation of the original data using a double arcsine transformation.
Proportion of rats which had any cells with any abnormality other than gaps: One-sided Fischers Exact test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
ambiguous
Toxicity:
no effects
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

The maximum concentration tested caused significant reductions in mitotic activity in the bone marrow of the
exposed animals. Small and non-dose related increases in 
the percentages of cells with chromosomal aberrations were
observed in the animals exposed to MMA. However, these 
increases were almost exclusively due to gap-type
aberrations and when these were excluded from the data 
small increases were only observed at 400 ppm. Such small 
increases, observed at lower, but not at higher
concentrations tested, are not considered to be 
biologically significant.

For further details, see attached document including 11 tables.

Applicant's summary and conclusion