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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: repeated dose
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 452 (Chronic Toxicity Studies)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 99.98%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Labs, Kingston, New York
- Age at study initiation: weanling rats
- Weight at study initiation: not reported
- Fasting period before study: none
- Housing: stainless steel, wire-mesh cages. Housed 3/cage upon arrival
- Diet (e.g. ad libitum): Purina Laboratory Chow Checkers #5001 (PLCC) available ad libitum except during exposures
- Water (e.g. ad libitum): ad libitum except during exposures
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±2°C
- Humidity (%): 50%±10%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
other: air
Details on exposure:
The study was designed to evaluate the potential chronic toxicity and oncogenicity of the test substance in male and female rats when exposed by inhalation. Reproductive organs were examined during histopathology examinations at 6-, 12-, 18-month, and 2-year sacrifices.
Details on mating procedure:
Animals were not mated.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Chamber atmospheres were analyzed by a GC every half hour during the 6 hour daily exposure period.
Duration of treatment / exposure:
2 years
Frequency of treatment:
6 hours/day, 5 days/week (excluding holidays)
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 0.2, 1.0, 2.5 % DME vapors
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0. 0.21, 1.02, 2.47% DME vapors
Basis:
analytical conc.
No. of animals per sex per dose:
100 male and 100 female per dose group
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
Reproductive organs were examined during histopathology examinations at 6-, 12-, 18-month, and 2-year sacrifices.
Statistics:
The incidences of gross and histopathological lesions were compared to control group incidences by the Fisher's Exact test.

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
2.5 other: %
Sex:
male/female
Basis for effect level:
other: No adverse effects on reproductive organs or tissues were observed at the highest concentration tested.
Remarks on result:
other: Generation not specified (migrated information)

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

No compound-related effects on the reproductive organs of either male or female rats were observed.  An increase in the incidence of mammary tumors (benign or malignant) was observed in female rats in the 2.5% exposure group.  The incidence of mammary tumors was considered not to be compound related because the incidences of tumors in the control group were uncharacteristically low in comparison with the control groups incidence in studies previously conducted at Haskell Laboratory.  See Section 7.7 for additional details regarding incidence levels and historical control data.

Applicant's summary and conclusion

Conclusions:
No adverse effects on reproductive organs or tissues at concentrations of 2.5% (highest concentration tested).

The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

A 2-year inhalation study was conducted in male and female rats (see Section 7.5.3 for details on the study design).  Ten rats/sex/group were sacrificed and necropsied at 6, 12, and 18 months and all rats alive at the 2-year time point. All rats underwent both gross and microscopic examinations. Reproductive organs included in the histopathological evaluation included testis, epididymis, prostate, seminal vesicles, cervix, mammary gland, ovary, uterus, and vagina. The testis was weighed.

No compound-related effects on the reproductive organs of either male or female rats were observed. An increase in the incidence of mammary tumors (benign or malignant) was observed in female rats in the 2.5% exposure group. The incidence of mammary tumors was considered not to be compound related because the incidences of tumors in the control group were uncharacteristically low in comparison with the control groups incidence in studies previously conducted at Haskell Laboratory.