Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive Toxicity Study:

In the three generations of male and female C57BL/6 mice, continuously, a diet containing10 % test chemical (equivalent to 0 or 5 g/kg bw/day; higher doses expected in pregnant females and in the post-weaning period of 10 g/kg bw/day). Four matings were performed in the F0 and F1 generations and three matings in the F2 generation. Pup weight at weaning was significantly reduced after exposure to both polysorbates. The number of live pups born, the viability index and the lactation index decreased. No effects on body weight gain of pregnant mice were observed, and no effects on organ weights of gonads or sperm motility were recorded. From the observations, The NOAEL for the test chemical in male and female C57BL/6 was observed to be 5000mg/kg in F0 genearation and LOAEL for F1 generation observed to be 5000mg/kg

Link to relevant study records
Reference
Endpoint:
three-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from EFSA journal.
Qualifier:
equivalent or similar to guideline
Guideline:
other: as mention below
Principles of method if other than guideline:
Higher doses of test chemical were administered in animals of three generation to examine the reproductive parameters.
GLP compliance:
no
Limit test:
yes
Justification for study design:
No Data Available
Specific details on test material used for the study:
- Molecular weight (if other than submission substance): 606.8318 g/mol
- Substance type: Organic
- Physical state: No Data Available
- Impurities (identity and concentrations): No Data Available
Species:
mouse
Strain:
other: C57BL/6
Details on species / strain selection:
No Data Available
Sex:
male/female
Details on test animals or test system and environmental conditions:
No Data Available
Route of administration:
oral: feed
Vehicle:
other: diet
Details on exposure:
No data available
Details on mating procedure:
Four matings were performed in the F0 and F1 generations and three matings in the F2 generation.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data Available
Duration of treatment / exposure:
No data available
Frequency of treatment:
No data available
Details on study schedule:
test chemical (equivalent to 0 or 5 g/kg bw/day; higher doses expected in pregnant females and in the post-weaning period of 10 g/kg bw/day).
Remarks:
5000mg/kgbw/day
10000mg/kg bw/day (post weaning period)
No. of animals per sex per dose:
No data
Control animals:
yes
Details on study design:
No data available
Positive control:
No data available
Parental animals: Observations and examinations:
No data available
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
No data available
Postmortem examinations (offspring):
No data available
Statistics:
No data available
Reproductive indices:
No data available
Offspring viability indices:
No data available
Clinical signs:
not examined
Dermal irritation (if dermal study):
not examined
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effects on body weight gain of pregnant mice were found
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Description (incidence and severity):
No effects on sperm motility were found
Reproductive performance:
effects observed, treatment-related
Description (incidence and severity):
lactation index decreased.
Dose descriptor:
NOAEL
Effect level:
5 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive function (sperm measures)
other: no effects on weight of male gonads
Remarks on result:
other: not specified
Critical effects observed:
not specified
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified
Dose descriptor:
other: not specified
Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
the no. of lice pus biorn, viability index decreased
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Pup weight at weaning was significantly reduced after exposure to test chemical
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
effects observed, treatment-related
Description (incidence and severity):
lactation index decreased.
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not examined
Dose descriptor:
LOAEL
Generation:
F1
Effect level:
5 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
other: Lactation index decreased
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
other: not specified
Generation:
other: not specified
Sex:
not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Reproductive effects observed:
not specified
Treatment related:
not specified
Conclusions:
The NOAEL for the test chemical in male and female C57BL/6 was observed to be 5000mg/kg F0 genearation and LOAEL for F1 generation observed to be 5000mg/kg
Executive summary:

In the three generations of male and female C57BL/6 mice, continuously, a diet containing10 % test chemical (equivalent to 0 or 5 g/kg bw/day; higher doses expected in pregnant females and in the post-weaning period of 10 g/kg bw/day). Four matings were performed in the F0 and F1 generations and three matings in the F2 generation. Pup weight at weaning was significantly reduced after exposure to both polysorbates. The number of live pups born, the viability index and the lactation index decreased. No effects on body weight gain of pregnant mice were observed, and no effects on organ weights of gonads or sperm motility were recorded. From the observations, The NOAEL for the test chemical in male and female C57BL/6 was observed to be 5000mg/kg in F0 genearation and LOAEL for F1 generation observed to be 5000mg/kg

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
5 000 mg/kg bw/day
Study duration:
subchronic
Species:
mouse
Quality of whole database:
The data is from a Klimisch 2 database.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive Toxicity Study:

The following data is from different studies of the test chemicals:

Reproductive Toxicity Study 1:

In the three generations of male and female C57BL/6 mice, continuously, a diet containing10 % test chemical (equivalent to 0 or 5 g/kg bw/day; higher doses expected in pregnant females and in the post-weaning period of 10 g/kg bw/day). Four matings were performed in the F0 and F1 generations and three matings in the F2 generation. Pup weight at weaning was significantly reduced after exposure to both polysorbates. The number of live pups born, the viability index and the lactation index decreased. No effects on body weight gain of pregnant mice were observed, and no effects on organ weights of gonads or sperm motility were recorded. From the observations, The NOAEL for the test chemical in male and female C57BL/6 was observed to be 5000mg/kg in F0 genearation and LOAEL for F1 generation observed to be 5000mg/kg.

Reproductive Toxicity Study 2:

In the present study, the two years experimental study carried out. The Wistar rats (F0 generation) fed to different test chemical level 5, 10 and 20% i.e (2500000, 5000000 and 10000000mg/kg), the next generation from different dose levels divided to groups of 12 males and 20 females and fed with same dose levels. The F0 generation and descending 2 generations observed for change in body weight, the efficiency of food utilization (EFU) as well as the efficiency of caloric utilization (ECU), hematology , urinalysis, Reproductive performance, lactation response gross and histopathology examination.The results of the study revealed, no treatment related weight gain in treated animals, the efficiency of food utilization (EFU) as well as the efficiency of caloric utilization (ECU) were somewhat higher in the initial (F0) generation than in the succeeding generations (F1 and F2 ). No chnage innhematological parameters, urinalysis, reproductive performance and lactation respose in initial and succeeding generations (F1 and F2). On the basis of the observed results the NOAEL for the test chemical observed to be 10000000mg/kg.

Effects on developmental toxicity

Description of key information

Developmental Toxicity Study:

The present study aimed, to examine the teratogenic potential of test chemical given to pregnant rats during the organogenetic period. The mating was done by using Virgin female rats of about 12 weeks of age were mated for 15 hours with male rats of same strain. The day when the spermatozoa in the vagina was detected was considered to be day 0 of pregnancy. In this study the pregnant Wistar rats were given test chemical at a dose of 0, 0.1 (99 mg/kg), 1.0 (960 mg/kg) or 10% (7693 mg/kg) in the diet from day 7 to day 14 of pregnancy. The treated female rats observed for evidence of clinical signs of toxicity and weighed daily. On day 20 of pregnancy, the pregnant rats in each group were killed by cervical dislocation. The peritoneal cavity and uterus were opened, and the numbers and positions of live and dead fetuses and resorptions were recorded. The live fetuses removed from the uterus by cesarean section were sexed, weighed and inspected for external anomalies and anomalies within the oral cavity. About half of the fetuses in each litter were fixed in alcohol, cleared in KOH solution, stained with Alizarin Red S14 and examined for skeletal anomalies. The remaining half of the fetuses in each litter were fixed in Bouin's solution, sectioned with razor blade and examined for internal anomalies.The results of the study revealed, No significant difference in the maternal body weight gain during the treatment period between the treated and control groups. The maternal developmental toxicity results revealed, the incidences of intrauterine death in the 1.0 % (960mg/kg) group were significantly higher than that of the control group however no such effects were seen in treated group at 96 and 7693mg/kg. In the 99mg/kg group, the number of implantations per litter was significantly higher than that of the control group. The incidences of resorptions in the 1.0 % (960mg/kg) group were significantly higher than that of the control group. No significant effect on number of resorptions were observed in treated and control animals. No significant effect were observed in live and dead fetuses per litter in  treated and control animals. No change in the sex ratio of live fetuses and the fetal body weight of both sexes. No other maternal toxicty effects were observed. When the fetuses toxicity examined no change in the sex ratio of live fetuses and the fetal body weight of both sexes weight were observed. Neither external, skeletal and vesceral anomalies were observed in any treated groups at 99, 960 and 7693mg/kg. Thus, based on the observations and results of the study, the NOAEL for the test chemical was considered to be 7693mg/kg in Wistar rats.


Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from publication.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
To examine the teratogenic potential of test chemical given to pregnant rats during the organogenetic period.
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
- Substance type: Organic
- Physical state: Liquid
Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
Details on test animals and env. conditions
TEST ANIMALS
- Source: No Data Available
- Age at study initiation: 12 weeks of age
- Weight at study initiation: (P) No Data
- Fasting period before study: No Data Available
- Housing: No Data Available
- Use of restrainers for preventing ingestion (if dermal): No
- Diet (e.g. ad libitum): basal diet (CE-2, Drug Clea Japan Inc., Tokyo) and tap water ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24+/- 1 oC
- Humidity (%): 55+/- 5 %.
- Air changes (per hr): No data Available
- Photoperiod (hrs dark / hrs light): No Data Available
Route of administration:
oral: feed
Vehicle:
other: feed
Details on exposure:
Pregnant rats were given test chemical at a dose of 0, 0.1 (99 mg/kg), 1.0 (960 mg/kg) or 10% (7693 mg/kg)of test chemical in the diet from day 7 to day 14 of pregnancy.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data available
Details on mating procedure:
Virgin female rats of about 12 weeks of age were mated for 15 hours with male rats of same strain. The day when the spermatozoa in the vagina was detected was considered to be day 0 of pregnancy.
Duration of treatment / exposure:
Days 7-14 of gestation
Frequency of treatment:
Daily
Duration of test:
No data
Remarks:
Doses / Concentrations:
0, 0.1, 1.0 or 10%
Basis:
0.1% (99 mg/kg), 1.0% (960 mg/kg) or 10% (7693 mg/kg)
No. of animals per sex per dose:
No data
Control animals:
yes, plain diet
Details on study design:
No data available
Maternal examinations:
The pregnant rats were observed for evidence of clinical signs of toxicity and weighed daily.
Ovaries and uterine content:
The peritoneal cavity and uterus were opened, and the numbers and positions of live and dead fetuses and resorptions were recorded.23
Fetal examinations:
The live fetuses removed from the uterus by cesarean section were sexed, weighed and inspected for external anomalies and anomalies within
the oral cavity.

About half of the fetuses in each litter were fixed in alcohol, cleared in KOH solution, stained with Alizarin Red S14 and examined for skeletal anomalies.

The remaining half of the fetuses in each litter were fixed in Bouin's solution, sectioned with a razor blade and examined for internal anomalies
Statistics:
Statistical analysis of the data was carried out using the litter as a unit.Student's t-test, Wilcoxon's rank sum test, chi-square test with Yates' correction or Fisher's exact probability test was used. The level of significance chosen was p < 0.05.
Indices:
No data available
Historical control data:
No data available
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant difference was noted in the maternal body weight gain during the treatment period between the treated and control groups.
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Number of abortions:
effects observed, non-treatment-related
Description (incidence and severity):
The incidences of intrauterine death in the 1.0 % (960mg/kg) group were significantly higher than that of the control group
Pre- and post-implantation loss:
effects observed, non-treatment-related
Description (incidence and severity):
In the 99 mg/kg group, the number of implantations per litter was significantly higher than that of the control group.
Total litter losses by resorption:
effects observed, non-treatment-related
Description (incidence and severity):
The incidences of resorptions in the 1.0 % (960mg/kg) group were significantly higher than that of the control group. No significant effect on number of resorptions were observed in treated and control animals.
Early or late resorptions:
effects observed, non-treatment-related
Description (incidence and severity):
The incidences of resorptions in the 1.0 % (960mg/kg) group were significantly higher than that of the control group. No significant effect on number of resorptions were observed in treated and control animals.
Dead fetuses:
no effects observed
Description (incidence and severity):
No significant effect were observed in live and dead fetuses per litter in treated and control animals.
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Other effects:
not specified
Details on maternal toxic effects:
Maternal toxic effects:no effects
Dose descriptor:
NOAEL
Effect level:
960 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
dead fetuses
early or late resorptions
effects on pregnancy duration
food consumption and compound intake
maternal abnormalities
number of abortions
organ weights and organ / body weight ratios
pre and post implantation loss
total litter losses by resorption
Remarks on result:
other: Not Specified
Abnormalities:
not specified
Fetal body weight changes:
no effects observed
Description (incidence and severity):
No change in the fetal body weight of both sexes were seen in any group at 99, 960 and 7693mg/kg
Reduction in number of live offspring:
not specified
Changes in sex ratio:
no effects observed
Description (incidence and severity):
No change in the sex ratio of live fetuses of both sexes in any group at 99, 960 and 7693mg/kg
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
Neither external anomalies were found in any group at 99, 960 and 7693mg/kg
Skeletal malformations:
no effects observed
Description (incidence and severity):
Neither skeletal anomalies were found in any group at 99, 960 and 7693mg/kg
Visceral malformations:
no effects observed
Description (incidence and severity):
No visceral abnirmalities were seen in any group at 99, 960 and 7693mg/kg
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects
Dose descriptor:
NOAEL
Effect level:
7 693 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: teratogenicity
Remarks on result:
other: not specified
Abnormalities:
not specified
Localisation:
other: not specified
Description (incidence and severity):
not specified
Developmental effects observed:
not specified
Treatment related:
not specified
Conclusions:
Based on the observations the NOAEL for the test chemical was considered to be 7693mg/kg in Wistar rats
Executive summary:

The present study aimed, to examine the teratogenic potential of test chemical given to pregnant rats during the organogenetic period. The mating was done by using Virgin female rats of about 12 weeks of age were mated for 15 hours with male rats of same strain. The day when the spermatozoa in the vagina was detected was considered to be day 0 of pregnancy. In this study the pregnant Wistar rats were given test chemical at a dose of 0, 0.1 (99 mg/kg), 1.0 (960 mg/kg) or 10% (7693 mg/kg) in the diet from day 7 to day 14 of pregnancy. The treated female rats observed for evidence of clinical signs of toxicity and weighed daily. On day 20 of pregnancy, the pregnant rats in each group were killed by cervical dislocation. The peritoneal cavity and uterus were opened, and the numbers and positions of live and dead fetuses and resorptions were recorded. The live fetuses removed from the uterus by cesarean section were sexed, weighed and inspected for external anomalies and anomalies within the oral cavity. About half of the fetuses in each litter were fixed in alcohol, cleared in KOH solution, stained with Alizarin Red S14 and examined for skeletal anomalies. The remaining half of the fetuses in each litter were fixed in Bouin's solution, sectioned with razor blade and examined for internal anomalies.The results of the study revealed, No significant difference in the maternal body weight gain during the treatment period between the treated and control groups. The maternal developmental toxicity results revealed, the incidences of intrauterine death in the 1.0 % (960mg/kg) group were significantly higher than that of the control group however no such effects were seen in treated group at 96 and 7693mg/kg. In the 99mg/kg group, the number of implantations per litter was significantly higher than that of the control group. The incidences of resorptions in the 1.0 % (960mg/kg) group were significantly higher than that of the control group. No significant effect on number of resorptions were observed in treated and control animals. No significant effect were observed in live and dead fetuses per litter in  treated and control animals. No change in the sex ratio of live fetuses and the fetal body weight of both sexes. No other maternal toxicty effects were observed. When the fetuses toxicity examined no change in the sex ratio of live fetuses and the fetal body weight of both sexes weight were observed. Neither external, skeletal and vesceral anomalies were observed in any treated groups at 99, 960 and 7693mg/kg. Thus, based on the observations and results of the study, the NOAEL for the test chemical was considered to be 7693mg/kg in Wistar rats.


Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
7 693 mg/kg bw/day
Study duration:
chronic
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Additional information

Developmental Toxicity Study:

The following data is from different studies of the test chemicals:

Developmental Toxicity Study 1:

The present study aimed, to examine the teratogenic potential of test chemical given to pregnant rats during the organogenetic period. The mating was done by using Virgin female rats of about 12 weeks of age were mated for 15 hours with male rats of same strain. The day when the spermatozoa in the vagina was detected was considered to be day 0 of pregnancy. In this study the pregnant Wistar rats were given test chemical at a dose of 0, 0.1 (99 mg/kg), 1.0 (960 mg/kg) or 10% (7693 mg/kg) in the diet from day 7 to day 14 of pregnancy. The treated female rats observed for evidence of clinical signs of toxicity and weighed daily. On day 20 of pregnancy, the pregnant rats in each group were killed by cervical dislocation. The peritoneal cavity and uterus were opened, and the numbers and positions of live and dead fetuses and resorptions were recorded. The live fetuses removed from the uterus by cesarean section were sexed, weighed and inspected for external anomalies and anomalies within the oral cavity. About half of the fetuses in each litter were fixed in alcohol, cleared in KOH solution, stained with Alizarin Red S14 and examined for skeletal anomalies. The remaining half of the fetuses in each litter were fixed in Bouin's solution, sectioned with razor blade and examined for internal anomalies.The results of the study revealed, No significant difference in the maternal body weight gain during the treatment period between the treated and control groups. The maternal developmental toxicity results revealed, the incidences of intrauterine death in the 1.0 % (960mg/kg) group were significantly higher than that of the control group however no such effects were seen in treated group at 96 and 7693mg/kg. In the 99mg/kg group, the number of implantations per litter was significantly higher than that of the control group. The incidences of resorptions in the 1.0 % (960mg/kg) group were significantly higher than that of the control group. No significant effect on number of resorptions were observed in treated and control animals. No significant effect were observed in live and dead fetuses per litter in  treated and control animals. No change in the sex ratio of live fetuses and the fetal body weight of both sexes. No other maternal toxicty effects were observed. When the fetuses toxicity examined no change in the sex ratio of live fetuses and the fetal body weight of both sexes weight were observed. Neither external, skeletal and vesceral anomalies were observed in any treated groups at 99, 960 and 7693mg/kg. Thus, based on the observations and results of the study, the NOAEL for the test chemical was considered to be 7693mg/kg in Wistar rats.

Developmental Toxicity Study 2:

The present study aimed to evaluate the developmental toxicity of the test chemical in pregnant CD-1 mouse. All experiment were conducted in two phases: an initial dose-finding study, followed by a reproductive phase which employed a single dose level for test chemical. For dose-finding,  test chemical was tested at five dose levels using ten virgin female mice per group. Treatment were administered once daily for 8 consecutive days, with a dosing volume determined on the basis of body weights on the first treatment day. Mice were observed twice daily during treatment, and once daily for 8 days following treatments. Body weights were recorded on the first and last (eighth) day of treatment, and on days 4 and 8 post-treatment. For the reproductive phase, the LD10 predicted on the basis of dose-finding results was the single dose used. Treatment in the reproductive phase were administered once daily on gd 6-13, with a dosing volume determined on the basis of pretreatment body weights on gd 6. The Mice were observed twice daily during treatment, and once daily on gd 14-17. Body weights were again recorded on gd 17. At the daily observation, signs of toxicity were recorded. Beginning on gd 18, mice were observed twice daily for signs of parturition. When delivery was judged to be complete (postnatal day l), the number of live pups was recorded, and live pups were weighed together as a litter, Neither live nor dead pups were systematically examined for malformations. Two days later (postnatal day 3), live pups were again counted and weighed as a litter, and maternal body weights were recorded. Dams and litters were then discarded. Females that failed to deliver a litter by the presumed gd 22 were killed and uteri were examined. If there was no gross evidence of a failed pregnancy, uteri were placed in 10% ammonium or sodium sulfide to reveal implantation sites as evidence of early termination of pregnancy. The results of the study revealed, No signs of maternal toxicity and no effects on maternal survival. No effects on maternal weight  were observed. No effects on pup survival were recorded. No change on pup survival and birth weight but decreased postnatal pup weight gain were seen and no external, skeletal and visceral abnormalities were recorded at 52000mg/kg dose of test chemical. From the observations and results the NOAEL for the test chemical considered to be 52000mg/kg bw/day in CD-1 mice.

Justification for classification or non-classification

Based on all the observations and results of the data available, the test chemical may not be classified as reproductive and developmental toxicant according to CLP regulation.

Additional information

Categories Display