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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: 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: This is only a short summary of the repeated dose toxicity study related to the reproductive organs, the full study can be found in section 7.5.2
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Principles of method if other than guideline:
Chronic repeated dose toxicity test including macroscopically and gross pathologically assessment of the reproductive organs and tissues.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Monomeric 4,4'-methylenediphenyl diisocyanate (Desmodur 44 M Schuppen from Bayer AG, Leverkusen); 13 batches were tested (purity: >99.5 %)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
See section 7.5.2a Hoymann et al 1995 (rat, 2y)

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
See section 7.5.2a Hoymann et al 1995 (rat, 2y)
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 7.5.2a Hoymann et al 1995 (rat, 2y)
Duration of treatment / exposure:
up to 2 years
Frequency of treatment:
17 hours per day; 5 days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.2, 0.7, 2.1 mg/m3
Basis:
nominal conc.
No. of animals per sex per dose:
80 females per dose; at each dose level there were additional 80 rats per group in satellite groups for : chronic toxicity over 12 months (20 animals); lung function over 20 months (12 animals); lung clearance over 20 months (8 animals); bronchoalveolar lavage, biochemistry over 3 months +1 week recovery (20 animals); bronchoalveolar lavage, biochemistry over 12 months + 1 week recovery (20 animals).
Control animals:
yes, sham-exposed
Details on study design:
See section 7.5.2a Hoymann et al 1995 (rat, 2y)

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Full pathological examination was done on 20 rats/dose of a 12 months exposure group and 20 rats/dose of a 24 months exposure group. Reproductive organs assessed included e.g. adrenals, ovaries, uterus, vagina and mammary gland. Compound-related changes were found in the respiratory tract(LOAEC 0.23 mg/m³), but no treatment related findings on reproductive or any other systemic organ effects were reported.

Applicant's summary and conclusion

Executive summary:

In a further chronic inhalation study with respirable aerosols of 4,4’-MDI, 80 female rats per dose group were whole-body exposed to atmospheres of 0.23, 0.70 or 2.05 mg/m³ for 17 hours/day, 5 days /week for up to 24 months. Full pathological examination was done on 20 rats/dose of a 12 months exposure group and 20 rats/dose of a 24 months exposure group. Reproductive organs assessed included e.g. adrenals, ovaries, uterus, vagina and mammary gland. Again compound-related changes were found in the respiratory tract(LOAEC 0.23 mg/m³), but no treatment related findings on reproductive or any other systemic organ effects were reported (Hoymann et al. 1995; see repeated dose toxicity).