1,1'-Methylenebis(4-isocyanatobenzene) and its oligomeric reaction products with [(methylethylene)bis(oxy)]dipropanol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Falling short of highest standards concerning aspects of protocol or reporting. Acceptable literature publication. Useful: supporting data.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Untersuchungen zur Stabilitat aromatischer Diisocyanat in Dimethylsulphoxid |(DMSO): Toluylendiisocyanat (TDI) und Diphenylmethandiisocyanat (MDI) im Ames-Test

Author:

Gahlmann R, Herbold B, Ruckes A & Seel K

Year:

1993

Bibliographic source:

Zbl.Arbeitsmed. 43: 34-38

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

Pre-dates, but is similar to, those of 84/449/EEC, B12, and OECD Test Guideline 474.

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-methylenediphenyl diisocyanate

EC Number:

202-966-0

EC Name:

4,4'-methylenediphenyl diisocyanate

Cas Number:

101-68-8

Molecular formula:

C15H10N2O2

IUPAC Name:

1,1'-methylenebis(4-isocyanatobenzene)

Constituent 2

Reference substance name:

benzene, 1,1'- methylenebis[4-isocyanato-

IUPAC Name:

benzene, 1,1'- methylenebis[4-isocyanato-

Details on test material:

4,4'-diphenylmethane diisocyanate in dimethyl sulphoxide,
suspended in corn oil before use.

Test animals

Species:

mouse

Strain:

ICR

Sex:

not specified

Administration / exposure

Route of administration:

intraperitoneal

Duration of treatment / exposure:

24 hour

Doses / concentrations

Remarks:

Doses / Concentrations:
0-200 mg MDI/kg
Basis:

Results and discussion

Test results

Sex:

not specified

Additional information on results:

An acute toxicity test gave a 7 day LD50 of about 100 mg/kg.
There were no deaths within 24 hr.
It was concluded that the test substance did not cause micronuclei, and therefore did not induce in vivo chromosomal aberration.
The number of erythrocytes with micronuclei differed little between treated groups and the solvent control.
The only statistically significant decrease in polychromatic erythrocytes occurred when the test substance was used at 200 mg/kg. This was taken to suggest inhibited myelopoietic function of the bone marrow.
When compared with distilled water, dimethyl sulphoxide in corn oil gave a statistically insignificant reduction in polychromatic erythrocytes, and increase in erythrocytes with micronuclei.