Registration Dossier
Registration Dossier
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EC number: 500-020-4 | CAS number: 9005-67-8 1 - 6.5 moles ethoxylated
Endpoint summary
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
- 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
Reference
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
- 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.
Reference
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.
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