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Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Version / remarks:
July 2016
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Duration of treatment / exposure:
males: 28 days; females: 54 days
Frequency of treatment:
once daily
Dose / conc.:
1 000 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
No. of animals per sex per dose:
10 males and 10 females per dose and control group
Control animals:
yes, concurrent vehicle
Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
food efficiency
water consumption and compound intake
ophthalmological examination
haematology
clinical biochemistry
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
histopathology: neoplastic
reproductive function (oestrous cycle)
reproductive function (sperm measures)
reproductive performance
Anogenital distance (AGD):
no effects observed
Nipple retention in male pups:
no effects observed
Key result
Dose descriptor:
NOEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
sexual maturation
clinical signs
mortality
body weight and weight gain
gross pathology
other: sexual maturation
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no
Conclusions:
The No Observed Effect Level (NOEL) in an oral screening study for reproductive toxicity was at 1000 mg/kg bw/day in rats.
Executive summary:

In a combined repeated dose toxicity study with reproduction/developmental toxicity screening test in rats via the oral route, conducted according to current OECD guideline 422 and in compliance with GLP, no changes attributable to treatment were noted for the examined reproductive toxicity parameters at 100, 300 or 1000 mg/kg bw/day. There was no effect of treatment on estrous cycle during the pre-pairing phase of the study or at termination. Mating performance as assessed by the number of paired animals that mated was unaffected. There was no effect on fertility, as assessed by the number of females that achieved pregnancy. The intergroup distribution of gestation length observed during the study did not indicate any obvious effect of treatment. The NOEL was 1000 mg/kg bw/day.

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
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A higher-tier fertility study (two-generation study) is not required at this tonnage band, since there were no adverse effects observed in the repeated dose toxicity study in reproductive organs or tissues or any adverse effects in the screening study for reproductive/developmental toxicity (OECD 422).


Short description of key information:
Reproduction / Developmental Toxicity Screening: rat (Wistar) male/female, gavage (OECD Guideline 422): NOAEL (P and F1): >= 1000 mg/kg bw/day (male/female)

Justification for selection of Effect on fertility via oral route:
OECD guideline study, no deviations, GLP

Effects on developmental toxicity

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: Combined Repeat Dose Toxicity Study with Reproduction/Developmental Toxicity Screening Test in the Rat (OECD 422)
Version / remarks:
2016
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Limit test:
no
Species:
rat
Strain:
Wistar
Route of administration:
oral: gavage
Vehicle:
water
Frequency of treatment:
once daily
Control animals:
yes, concurrent vehicle
Key result
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
behaviour (functional findings)
body weight and weight gain
changes in number of pregnant
changes in pregnancy duration
clinical biochemistry
clinical signs
dead fetuses
early or late resorptions
effects on pregnancy duration
food consumption and compound intake
food efficiency
gross pathology
haematology
histopathology: neoplastic
histopathology: non-neoplastic
mortality
necropsy findings
neuropathology
number of abortions
ophthalmological examination
organ weights and organ / body weight ratios
pre and post implantation loss
total litter losses by resorption
water consumption and compound intake
Key result
Key result
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reduction in number of live offspring
changes in sex ratio
fetal/pup body weight changes
changes in litter size and weights
changes in postnatal survival
external malformations
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
The No Observed Effect Level (NOEL) in an oral screening study for developmental toxicity was 1000 mg/kg bw/day in rats.
Executive summary:

In a combined repeated dose toxicity study with reproduction/developmental toxicity screening test in rats via the oral route, conducted according to current OECD guideline 422 and in compliance with GLP, no changes attributable to treatment were noted in offspring. There was no effect of maternal treatment on the number of implantations, post-implantation loss and live birth index, sex ratio, and subsequent offspring survival to day 13 of age at dosages of 100, 300 or 1000 mg/kg bw/day. There was also no effect of treatment with the test substance on offspring growth and development, indicated by clinical signs, offspring body weight or body weight gain, visible nipple count in male offspring on day 13 post partum, or ano-genital distance at 100, 300 or 1000 mg/kg bw/day. The NOEL was 1000 mg/kg bw/day.

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
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, the test substance does not require classification for reproductive or developmental toxicity according to the CLP Regulation (EC) No 1272/2008.

Additional information

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