Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
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
Qualifier:
no guideline followed
Principles of method if other than guideline:
see below
GLP compliance:
no
Limit test:
no
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
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.
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
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
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: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Dose descriptor:
NOAEL
Effect level:
90 other: mg/animal/day
Sex:
male/female
Remarks on result:
other: Generation: P to F3 generation (migrated information)
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
Reproductive effects observed:
not specified
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.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
Study duration:
chronic
Species:
rat
Quality of whole database:
NOAEL: 90 mg/rat/day
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In a multi-generation study, male and 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.

Effects on developmental toxicity

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Unpublished data cited in a peer-reviewed publication
Qualifier:
no guideline followed
Principles of method if other than guideline:
see below
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
other: FB30
Details on test animals and environmental conditions:
Age at study initiation: 10-14 weeks
Weight at study initiation: 200-250 g
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
no
Details on mating procedure:
not further specified
Duration of treatment / exposure:
days 6-15 of gestation
Frequency of treatment:
continuously via drinking water
Duration of test:
not further specified
Remarks:
Doses / Concentrations:
0.01, 0.1 and 1 % in drinking water (ca. 34, 351 and 3204 mg/rat/day)
Basis:

No. of animals per sex per dose:
10 f
Control animals:
yes
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: No data
WATER CONSUMPTION AND COMPOUND INTAKE: Yes
POST-MORTEM EXAMINATIONS: Yes
Ovaries and uterine content:
not further specified
Fetal examinations:
not further specified
Statistics:
no data
Indices:
not further specified
Details on maternal toxic effects:
Maternal toxic effects:no effects
Dose descriptor:
NOAEL
Effect level:
3 204 other: mg/rat/day
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects
Dose descriptor:
NOAEL
Effect level:
3 204 other: mg/rat/day
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEL
Effect level:
3 204 other: mg/rat/day
Basis for effect level:
other: embryotoxicity
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
In this study with female FB30 rats, the dosing with up to 3204 mg/rat/day via drinking water from day 6-15 of gestation caused no maternal toxicity or embryotoxic and teratogenic effects.
Executive summary:

In this study with female FB30 rats, the dosing with up to 3204 mg/rat/day via drinking water from day 6-15 of gestation caused no maternal toxicity or embryotoxic and teratogenic effects.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
Study duration:
subacute
Species:
rat
Quality of whole database:
NOAEL: 3204 mg/rat/day
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In a study with female rats, the dosing with up to 3204 mg/rat/day via drinking water from day 6-15 of gestation caused no maternal toxicity or embryotoxic and teratogenic effects.

Justification for classification or non-classification

Based on the negative results obtained, no classification according to EU and GHS criteria is required.