4,4'-methylenediphenyldiisocyanate and 2,4'-diisocyanatodiphenylmethane and their oligomerisation reaction products with 2,2'-oxydiethanol, propane-1,2-diol and butane-1,3-diol

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: Sub-chronic repeated dose toxicity test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Acute, Subacute, and Subchronic Inhalation Toxicity Studies of Respirable Polymeric Methylene Diphenyl Diisocyanate (Polymeric MDI) Aerosol in Rats

Author:

Reuzel PGJ, Kuper CF, Feron VJ, Appelman LM and Löser E

Year:

1994

Bibliographic source:

Fundamental and applied toxicology 22, 186-194

Materials and methods

Principles of method if other than guideline:

Sub chronic repeated dose toxicity test including macroscopically and gross pathologically assessment of the reproductive organs and tissues.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

9016-87-9

Cas Number:

9016-87-9

IUPAC Name:

9016-87-9

Constituent 2

Reference substance name:

Isocyanic acid, polymethylenepolyphenylene ester

IUPAC Name:

Isocyanic acid, polymethylenepolyphenylene ester

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Details on test material:

Polymeric methylene diphenyl diisocyanate (pMDI) was supplied by Bayer AG, Leverkusen. It is a viscous (200 ± 40 mP), dark brown liquid with the following composition and trace impurities (%, w/w) as specified by the supplier: -N=C=O (isocyanate) content, 30±2: monomeric MDI content,52 ± 3: hydrolysable chlorine, -< 0.3: total chlorine, -<0.8; chloro-benzene, -<0.015; phenyl isocyanate, -<0.005 ± 0.001 :and sediment content, -<0.01.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

See section 7.5.2c Reuzel et al 1994 (rat, 90d)

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

whole body

Vehicle:

unchanged (no vehicle)

Details on exposure:

See section 7.5.2c Reuzel et al 1994 (rat, 90d)

Details on mating procedure:

Not included in the test as this is a repeated dose test.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

See section 7.5.2c Reuzel et al 1994 (rat, 90d)

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6hr/day, 5 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 0.35, 1.4 or 7.2 mg respirable polymeric MDI/m3 for SC1
Basis:
analytical conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 4.1, 8.4 or 12.3 mg respirable polymeric MDI/m3 for SC2
Basis:
analytical conc.

No. of animals per sex per dose:

15

Control animals:

yes

Details on study design:

See section 7.5.2c Reuzel et al 1994 (rat, 90d)

Examinations

Postmortem examinations (parental animals):

Reproductive organs and tissues were macroscopically and gross pathologically assessed at the autopsy. A detailed histopathological assessment was performed of 10 rats/sex of the control group and 20 rats/sex of the high-concentration group at the end of the exposure (week 14) and of 10 rats/sex of the control and high-concentration group at the end of the posttreatment period (in week 18).
Histopathological assessment included e.g. adrenals, epididymides, mammary glands, seminal vesicles, testes and uterus. Neither gross examination at autopsy nor histopathological assessment revealed any treatment related systemic effects. The only treatment related effects were confined to the respiratory tract (increased relative lung weight ratios in the mid- and high concentration groups, histopathological and microscopic changes in all pMDI exposed groups).

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Neither gross examination at autopsy nor histopathological assessment revealed any treatment related systemic effects. The only treatment related effects were confined to the respiratory tract (increased relative lung weight ratios in the mid- and high concentration groups, histopathological and microscopic changes in all pMDI exposed groups).

Applicant's summary and conclusion

Executive summary:

Reproductive organs and tissues were macroscopically and gross pathologically assessed at the autopsy. A detailed histopathological assessment was performed of 10 rats/sex of the control group and 20 rats/sex of the high-concentration group at the end of the exposure (week 14) and of 10 rats/sex of the control and high-concentration group at the end of the posttreatment period (in week 18).

Histopathological assessment included e.g. adrenals, epididymides, mammary glands, seminal vesicles, testes and uterus. Neither gross examination at autopsy nor histopathological assessment revealed any treatment related systemic effects. The only treatment related effects were confined to the respiratory tract (increased relative lung weight ratios in the mid- and high concentration groups, histopathological and microscopic changes in all pMDI exposed groups).