Registration Dossier

Toxicological information

Toxicity to reproduction

Currently viewing:

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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 0.35, 1.4 or 7.2 mg respirable polymeric MDI/m3 for SC1
Basis:
analytical conc.
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).