Registration Dossier

Administrative data

Endpoint:
multi-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1966
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older study described in sufficient detail, but not all endpoints according to recent standard protocols examined

Data source

Reference
Reference Type:
publication
Title:
Untersuchungen zur Toxikologie von Diaethylcarbonat
Author:
Bornmann G & Loeser A
Year:
1966
Bibliographic source:
Arch Toxicol 22, 98-114

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
see below
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Purity: > 99.5 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Weight at study initiation: 145-160 g
Housing: individually caging
Diet: ad libitum
Water: ad libitum

ENVIRONMENTAL CONDITIONS
Temperature (°C): 26-28

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
Drinking water solutions were prepared daily
Concentration in vehicle: 0, 0.015, 0.075 or 0.3 % (w/v)
Details on mating procedure:
the animals were mated for 20 days with daily changes of partner
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
breeding was done until F3 generation
Frequency of treatment:
continuously via drinking water
Details on study schedule:
After 9 weeks of treatment, 10 male and 10 female rats dosed with 0 or 0.015 % were mated for 20 days (daily changes of partner). After 27 weeks of treatment, groups of 10 rats dosed with 0.075 and 0.3 % were mated in the same way. For the F1 generation a comparable dosage/treatment regimen was used and at an appropriate age and weight they were used for breeding the F2-generation. The F3-generation was bred from the F2-generation in the same way.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.015, 0.075 or 0.3 % (ca. 0, 4, 22 or 90 mg/rat/day)
Basis:
nominal in water
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Positive control:
no

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS / CLINICAL OBSERVATIONS: Yes (not further specified)
BODY WEIGHT: Yes (not further specified)
HAEMATOLOGY: Yes (blood glucose)
Oestrous cyclicity (parental animals):
no data
Sperm parameters (parental animals):
not examined
Litter observations:
PARAMETERS EXAMINED: number of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain
GROSS EXAMINATION OF DEAD PUPS: abnormalities
Postmortem examinations (parental animals):
SACRIFICE: up to 10 m and 10 f from each generation
GROSS NECROPSY: yes
HISTOPATHOLOGY: yes (not described in detail)
ORGAN WEIGHTS: yes (pituitary, thyroid, adrenals, ovaries)
Postmortem examinations (offspring):
not described in detail
Statistics:
no data
Reproductive indices:
not described in detail
Offspring viability indices:
not described in detail

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
90 other: mg/animal/day
Sex:
male/female
Remarks on result:
other: Generation: P to F3 generation (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In a multi-generation study, groups of 10 male and 10 female Wistar rats were dosed with 0 - 0.3 % (up to 90 mg/rat/day) via drinking water. In none of the different generations (P to F3) adverse effects were seen and the dosing had no adverse effects on fertility or on foetal development.
Executive summary:

In a multi-generation study, groups of 10 male and 10 female Wistar rats were dosed with 0 - 0.3 % (up to 90 mg/rat/day) via drinking water. In none of the different generations (P to F3) adverse effects were seen and the dosing had no adverse effects on fertility or on foetal development.