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EC number: 309-928-3 | CAS number: 101357-30-6
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: OECD guideline 422. GLP study.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- other: 1.0% Methylcellulose
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 42 Days for males
14 Days before mating to day 4 of lactation for females - Frequency of treatment:
- Daily
- Remarks:
- Doses / Concentrations:
100 mg/kg/day
Basis:
actual ingested - Remarks:
- Doses / Concentrations:
300 mg/kg/day
Basis:
actual ingested - Remarks:
- Doses / Concentrations:
1000 mg/kg/day
Basis:
actual ingested - No. of animals per sex per dose:
- 12 male animals per group
12 female animals per group - Control animals:
- yes
- Parental animals: Observations and examinations:
- GENERAL STATE: Yes (appearance, behaviour, mortality)
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Before and after treatment, once a week.
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Time schedule for examinations: Weekly - Oestrous cyclicity (parental animals):
- - Estrous cycle
- Sperm parameters (parental animals):
- - Number of cells in seminiferous epithelia, testis weight, seminal vesicle weight and epididymis weight.
- Litter observations:
- PARAMETERS EXAMINED
The following parameters were examined in offspring:
number of pups born, delivery index (%), number of pups alive on Day 0 of lactation, live birth index (%), sex ratio, number of pups alive on Day 4 of lactation, viability index (%), body weight of live pups on Day 0.
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities - Postmortem examinations (parental animals):
- GROSS PATHOLOGY: Yes
ORGAN WEIGHTS: Yes
HISTOPATHOLOGY: Yes - Postmortem examinations (offspring):
- GROSS NECROPSY: yes
- Reproductive indices:
- Copulation index
Fertility index
Implantation index
Gestation index - Offspring viability indices:
- - Viability index
- 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:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Remarks:
- maternal toxicity
- Effect level:
- >= 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Histopathology changes observed at 1000 mg/kg bw/day (forestomach)
- Dose descriptor:
- NOAEL
- Remarks:
- reproduction toxicity
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- 99.5%
- 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:
- no effects observed
- Histopathological findings:
- no effects observed
- Dose descriptor:
- NOAEL
- Remarks:
- offspring development
- Generation:
- F1
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Reproductive effects observed:
- not specified
- Conclusions:
- The results were:
-NOAEL maternal toxicity >= 300 mg/kg bw /day
-NOAEL reproductive toxicity>= 1000 mg/kg bw/day
-NOAEL offspring development >= 1000 mg/kg bw/day - Executive summary:
The aim of the test was to study the reproductive and developmental toxicity in rats (12 males and 12 females) in a combined repeated dose toxicity study with the reproductive / developmental toxicity screening test at doses of 100, 300 and 1000 mg/kg bw/day.
The test was performed according to OECD Test Guideline 422.
The results were:
-NOAEL maternal toxicity >= 300 mg/kg bw /day
-NOAEL reproductive toxicity>= 1000 mg/kg bw/day
-NOAEL offspring development >= 1000 mg/kg bw/day
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The key study is GLP compliant and Klimisch score 1.
Additional information
Reproductive/Developmental toxicity screening test:
Key study. Study with 12 male/ 12 female rats at doses of 100, 300, 1000 mg/kg/day, according to OECD Test Guideline 422.
The result was as follows: fertility/reproductive toxicity NOAEL = 1000 mg/kg bw /day
Two-generation reproductive toxicity study:
In accordance with column 2 of REACH Annex IX, the two-generation reproductive toxicity study ( required in section 8.7.3) does not need to be conducted as the 28-day and 90-day study results do not indicate adverse effects on reproductive organs or tissues.
Short description of key information:
Fertility/ reproductive toxicity NOAEL= 1000 mg/kg bw , key study with 12 male/ 12 female rats, at doses of 100, 300, 1000 mg/kg/day, according to OECD Test Guideline 422.
Justification for selection of Effect on fertility via oral route:
Only one study available.
Effects on developmental toxicity
Description of key information
Developmental toxicity NOAEL= 1000 mg/kg bw , key study with 12 female rats, at doses of 100, 300, 1000 mg/kg/day, according to OECD Test Guideline 422.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The key study is GLP compliant and Klimisch score 1.
Additional information
Reproductive/Developmental toxicity screening test:
Key study. Study with 12 female rats at doses of 100, 300, 1000 mg/kg/day, according to OECD Test Guideline 422.
The result was as follows: developmental toxicity NOAEL = 1000 mg/kg bw /day
Pre-natal developmental toxicity study: The study does not need to be conducted since based on the available data from the reproduction/developmental toxicity screening test, the test material did not cause any adverse effects.
Justification for selection of Effect on developmental toxicity: via oral route:
Only one study available. See the attachment above.
Justification for classification or non-classification
Based on the available information:
fertility/reproductive toxicity NOAEL = 1000 mg/kg bw /day
developmental toxicity NOAEL = 1000 mg/kg bw /day
the substance is not classified.
Additional information
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