Formaldehyde, oligomeric reaction products with aniline

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting 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

Test material information

Constituent 1

Reference substance name:

4,4'-methylenedianilinium dichloride

EC Number:

236-934-2

EC Name:

4,4'-methylenedianilinium dichloride

Cas Number:

13552-44-8

Molecular formula:

C13H14N2.2ClH

IUPAC Name:

4,4'-methylenedianilinium dichloride

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

Test results

Sex:

male

Genotoxicity:

other: weak effects were recorded

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:

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.