Registration Dossier

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
according guideline

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on exposure:
The dose formulations were prepared weekly; addition of 80% PEG 300 to the substance and homogenized; dose volume of 5 ml/kg body weight with daily adjustment to the actual body weight;
Details on mating procedure:
- M/F ratio per cage: 1/1
- Length of cohabitation: 14 d
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as day 0 of pregnancy
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
HPLC/UV-detection
Duration of treatment / exposure:
mailes: 14-day pre-pairing period, pairing period + 1 day; minimum 4 weeks
females: 14-day pre-pairing period, pairing period, gestation, lactation period up to day 4 post partum; approximately 7 weeks;
Frequency of treatment:
once daily orally by gavage
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
50 mg/kg body weight/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
200 mg/kg body weight/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
1000 mg/kg body weight/day
Basis:
actual ingested
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily;

BODY WEIGHT: Yes
- Time schedule for examinations: daily

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

Litter observations:
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
external examination at first Litter Check and a last litter check (day 4); clinical signs and macroscopic findings; number and sex of pups, stillbirths, live births, postnatal mortality, weight gain to day 4 post partum;

Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All animals after pairing period
- Maternal animals: All animals on day 4 post partem


Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
clinical signs considered to be incidental
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
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
adrenocortical changes consisting of minimal hypertrophic changes of the zona fasciculate at 200 mg/kg/day ; at 200 and 1000 mg/kg/day, erythropoiesis at minimal degree was noted in two females in each group.
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS):
All animals survived

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS):
At all dose-levels, there were no treatment-related effects;


REPRODUCTIVE Data (PARENTAL ANIMALS):
At all dose-levels, there were no treatment-related effects on precoital time, mean duration of gestation, number of corpora lutea and implantaions, post-implantation loss, pup survival or litter size from birth through to scheduled sacrifice an day 4 post partum;


ORGAN WEIGHTS (PARENTAL ANIMALS)
No test item related changes were noted in mean organ weight of thymus, adrenals, testes and epididymides in males;

In males and females at 200 mg/kg/day and in females at 1000 mg/kg/day, adrenocortical changes consisting of minimal to moderate hypertrophic changes of the zona fasciculate were noted.

Effect levels (P0)

open allclose all
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: with respect to reproduction/ developement toxicity;
Dose descriptor:
NOEL
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: based on the higher locomotor activity;
Dose descriptor:
NOEL
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: based on erithropoieseis noted during the histopathology examination;

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:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not examined
Histopathological findings:
not examined

Details on results (F1)

no findings regarding first litter check and last last litter check (day 4), clinical signs and macroscopic findings in all groups;

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: fetal toxicity

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
no indication of reproduction toxicity;