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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Lacks compliance with contemporary guidelines and is insufficiently reported. However the results are considered to be adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Evaluation of a three-exposure mouse bone marrow micronucleus protocol: results with 49 chemicals
Author:
Shelby MD, Erexson GL, Hook GJ & Tice RR
Year:
1993
Bibliographic source:
Environ.Mol.Mutagen. 21: 160-79

Materials and methods

Type of assay:
other: Mouse bone marrow micronucleus

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
4,4’-MDA-dihydrochloride CAS 13552-44-8

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Corn oil
Details on exposure:
Groups of five mice were administered MDA by intraperitoneal injection on three consecutive days. Test doses were based on toxicity /mortality data from pre-studies. Doses for the micronucleus studies were the maximum tolerated dose, and one-half and one-quarted of that dose. Doses for MDA were 0, 9.3, 18.5 and 37 mg/kg bw.
Positive control(s):
Positive control and solvent control data are available.

Examinations

Tissues and cell types examined:
48-hrs after the third treatment animals were killed and bone marrow and peripheral blood smears prepared. Bone marrow smears from each animal were examined by fluorescence microscopy for determination of polychromatic erythrocytes.
2000 polychromatic erythrocytes were examined for micronucleus, and 200 erythrocytes examined for percent polychromatics.

Results and discussion

Any other information on results incl. tables

4,4'-Methylenedianiline (C) Positive

The initial test gave a trend P = .054 with MN-PCE frequencies ranging from 1.7 in control to 2.9 at the high dose of 37 mg/kg. The repeat test using the same doses gave significant trend test (P = .019) from 1.9 in control to 3.5 at 37 mg/kg. Based on the dose dependant increase in MN-PCE in the first test and the positive trend test in the second, overall results were considered positive.

Table 1. 4,4'-Methylene-dianiline 2HCl. CAS Number 13552-44-8

Tissue

Trend P value

Dose (mg/kg)

MN-PCE/1.000 (No. animals)

Pair-wise

Survival

% PCE

Bone marrow

0.054

0

1.70+/-0.20(5)

.

5/5

51.3

.

.

9.3

2.30+/-0.41(5)

0.1711

5/5

44.5

.

.

18.5

2.50+/-0.84(4)

0.1195

5/5

43.3

.

.

37

2.88+/-0.97(4)

0.0481

4/5

36.9

Bone marrow

0.019

0

1.90+/-0.19(5)

.

5/5

35.4

.

.

9.3

2.70+/-0.44(5)

0.1188

5/5

45.9

.

.

18.5

2.40+/-0.33(5)

0.2226

5/5

54.7

.

.

37

3.50+/-0.32(5)

0.0146

5/5

62.0

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: weak genotoxic effect
Industry does not have right to access the data. This study indicates some weak or inconclusive genotoxic activity in the test system. This is compatible with a variety of other published studies. As the official EU Classification of MDA is Category 3 mutagen and Category 2 carcinogen, it is considered that additional guideline studies are not required at this time.