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EC number: 261-873-3 | CAS number: 59709-10-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Effects on fertility
Description of key information
Reproductive Toxicity
Based on the data available from different studies, the No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day for reproductive toxicity, when rodents were treated with test material orally by gavage. Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- Experimental data from various test chemicals
- Justification for type of information:
- Weight of evidence approach based on the data of the read-across chemicals.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- WoE report is based on 2 reproductive toxicity studies i.e. WoE-2 and WoE-3.
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on species / strain selection:
- not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 2. - Source: Charles River Japan Co., Ltd
- Age at study initiation: 9 weeks
- Weight at study initiation: 309 to 355 g for males and from 206 to 232 g for females
- Fasting period before study: No data available
- Housing: Rat were housed stainless steel hanging type wire mesh cage, excluded for the period of pregnancy /nursing period. During pregnancy / nursing female were housed in polycarbonate cage with a floor covering for laboratory animals.
- Diet (e.g. ad libitum): Solid feed for experimental animals irradiated with ultraviolet rays after autoclave sterilized nd filtering with a pore size of 5 μm, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
-Temperature (°C): 22 ± 2 ° C.
- Humidity (%):55 ± 15%
- Air changes (per hr): 12 times / hour
- Photoperiod (hrs dark / hrs light): lighting 12 hours / day (7: 00-19: 00)
3. TEST ANIMALS
- Age at study initiation: 9 weeks - Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- other: 2. 0.5 % Sodium carboxymethylcellulose mixed with 0.1 % Tween 80 3. Water
- Details on exposure:
- 2. VEHICLE
- Justification for use and choice of vehicle (if other than water): 0.5 % Sodium carboxymethylcellulose mixed with 0.1 % Tween 80
- Concentration in vehicle: 0 (vehicle), 100, 300, 1000 mg/kg
- Amount of vehicle (if gavage): 10 mL / kg
3. PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with water at dose levels of 0, 40, 200 or 1000 mg/Kg/day (Recovery group: 0, 1000 mg/kg/day)
VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Concentration in vehicle: 0, 40, 200 or 1000 mg/Kg/day (Recovery group: 0, 1000 mg/kg/day) - Details on mating procedure:
- 2. - M/F ratio per cage: 1:1
- Length of cohabitation: 14th day
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Plug formation or sperm in vaginal smear referred to as day 0 of pregnancy
3. not specified - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- 2. not specified
3. yes - Spectrophotometer: UV-2400PC
The UV-visible absorption spectrum and the absorbance were measured. - Duration of treatment / exposure:
- 2. 42 to 47 days
3. Male: 42 days / - Female: 41 - 47 days (from 14 days before mating to day 4 of lactation) - Frequency of treatment:
- 2. Daily
3. Daily - Details on study schedule:
- 2. not specified
3. not specified - Remarks:
- 2. 0, 100, 300 and 1000 mg/kg bw/day
3. Test group: 0, 40, 200 or 1000 mg/Kg/day
Recovery group: 0, 1000 mg/kg/day - No. of animals per sex per dose:
- 2. Total: 96
0 (vehicle) mg/kg: 12 male, 12 female
100 mg/kg: 12 male, 12 female
300 mg/kg: 12 male, 12 female
1000 mg/kg: 12 male, 12 female
3. not specified - Control animals:
- yes, concurrent vehicle
- Details on study design:
- 2. - Dose selection rationale: Test substance was repeatedly administered orally to SD rats of 3 male and 3 female at 0, 100, 300 and 1000 mg / kg doses for 14 days, and as a result, No effect on in general condition, body weight, food consumption. No clear toxicity change due to administration of the test substance was observed in both organ weight and necropsy.
Based on these findings, the high dose was set at the upper limit of 1000 mg / kg prescribed in the OECD guidelines, three doses of 300 mg / kg for the medium dose and 100 mg / kg for the low dose were set at a tolerance of about 3 .
3. not specified - Positive control:
- 2. not specified
3. not specified - Parental animals: Observations and examinations:
- 2. Mortality, clinical sign, body weight and feed Consumption were examined.
3. DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data
BODY WEIGHT: Yes
- Time schedule for examinations: No data
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes - Oestrous cyclicity (parental animals):
- 2. Estrous cyclicity were examined.
Number of corpus luteums and the number of landings were examined
3. not specified - Sperm parameters (parental animals):
- 2. Not specified
3. not specified - Litter observations:
- 2. Not specified
3. not specified - Postmortem examinations (parental animals):
- 2. Hematology, clinical chemistry, Gross pathology and histopathology were examined.
3. SACRIFICE
- Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.]
- Maternal animals: All surviving animals [describe when, e.g. after the last litter of each generation was weaned.]
GROSS NECROPSY: Yes
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively. - Postmortem examinations (offspring):
- 2. Number of births, sex and Body weight were examined.
3. not specified - Statistics:
- 2. Regarding the weighing data, parametric data was tested for equal variance by the Bartlett method, and one-way ANOVA was performed when variance was equal. Where the variances are not equal and nonparametric data were tested by Kruskal-Wallis. When significant difference was observed between groups, multiple comparisons of Dunnett method or Dunnett type were performed. Pathological findings in counting data were examined by χ 2 for a × b . When significant difference was observed, comparison was made between control group and each test substance administered group by Armitage χ 2 test. Other counting data were tested by Fisher's direct stochastic method. The significance level of each test was 5%. For the data on newborn babies, the average value calculated for each mother was set as a sample unit.
3. not specified - Reproductive indices:
- 2. Breast feeding, nesting, and the presence or absence of feeding, birth rate, implantation rate, delivery rate were examined.
3. not specified - Offspring viability indices:
- 2. Viability on day 0 and 4 were examined.
3. not specified - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 2. effects observed, treatment-related - Red feces exhibiting the same color tone as the test substance administered in all sexes were observed daily from the day following the administration start date. When treated wtih 1000 mg/kg bw, in 2 male loose stools were observed transiently on 22 days after the start of administration, but abnormalities in general conditions considered to be toxic changes.
3. no effects observed - no evidence of toxicity attributable to the test substance in all test items for both sexes was observed. - Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- 2. no mortality observed - No effect on survival of treated male and female rat were observed as compared to control.
3. no mortality observed - Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - No significant effect on body weight and body weight gain of treated male and female rats were observed as compared to control.
3. no effects observed - In the 200 mg / kg group, female weight at birth was significantly higher than that in the vehicle control group.
Female weight at birth day in 40 and 1000 mg / kg groups, male weight at birth day in each treatment group and 4 days after birth, there was no significant difference in male and female body weight between the vehicle control group. - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - No effect on food consumption of treated male and female rats was observed as compared to control.
3. no effects observed - Male - In the measurement of food intake during the administration period, vehicle control was performed on day 29 in the 40 and 200 mg / kg administration groups. A significantly lower value was found compared to the group. During the recovery period, No significant difference was found between the 1000 mg / kg group and the vehicle control recovery group. Female - Before mating, during pregnancy and during the lactation period of the mother animal, each administration group is compared with the vehicle control group. There was no significant difference between them. Between the 1000 mg / kg dose group and the vehicle control recovery group in the recovery group that did not carry out mating. There was no significant difference. - Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 2. effects observed, non-treatment-related - When treated wtih 100 mg / kg, significant decrease in prothrombin time were observed in male rats, but no change was observed in the 300 and 1000 mg / kg group, so it was judged to be an accidental change. In females, there was no significant difference between the test substance administered group and the control group.
3. no effects observed - In the male 1000 mg / kg dose group, significant low values of AST and glucose, Significant highs, A significant increase in glucose was noted in the female 1000 mg / kg group. Also, In the female 1000 mg / kg group, hematological examination showed a significant increase in eosinophil ratio - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 2. effects observed, non-treatment-related - When treated wtih 1000 mg / kg, significant incrase in A / G ratio were observed in male rats. However, since the total protein and albumin were not changed and were slightly high, it was considered to be fluctuating within the physiological range and it was judged that it was not caused by administration of the test substance.
When treated wtih 100 mg / kg, significant incrase in ASAT (GOT) in female rats, but no change was observed in the 300 and 1000 mg / kg group, so it was judged to be an accidental change .
3. not specified - Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- 2. not specified
3. no effects observed - Both male and female, each administration at the end of the administration period and at the end of the recovery period, there was no significant difference between the group and the vehicle control group. - Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - No histopathological changes were observed in treated male and female rats as compared to control.
3. no effects observed - In histopathological examination, calcification of the pulmonary artery, hepatocellular necrosis in the liver, small granuloma in the liver, kidney, Visceral cyst formation, adrenal cortical vacuolation and intrastromal lymphocyte infiltration of the prostate were found in a few cases. In addition,histopathological changes observed in the histopathological examination of males in the 1000 mg / kg dose group - Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - No effect on sexual cycle of treated female rat were observed as compared to control.
3. not specified - Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - No significant difference was observed in mating index, fertility index, numbers of corpora lutea or implantations, implantation index, delivery index, gestation index, gestation length, parturition or maternal behavior, numbers of offspring or live offspring of treated rats as compared to control.
3. no effects observed - Pregnancy lupus number, implantation rate, birth rate, gestational age, parturition status and lactation status are increased by test substance administration.The number of implantations in the 1000 mg / kg dose group compared to the vehicle control group
There was a significant increase in the number of pregnant women, but the number of pregnant corpus corpora lutea and implantation rate differed between each treatment group and vehicle control group. Because there was no significant difference between the two, it is considered to be a change that has no toxicological significance. - Dose descriptor:
- NOAEL
- Remarks:
- 2
- 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
- haematology
- clinical biochemistry
- organ weights and organ / body weight ratios
- gross pathology
- histopathology: non-neoplastic
- reproductive function (oestrous cycle)
- reproductive performance
- Remarks on result:
- other: No effect observed
- Dose descriptor:
- NOAEL
- Remarks:
- 3
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- body weight and weight gain
- food consumption and compound intake
- haematology
- urinalysis
- histopathology: non-neoplastic
- reproductive performance
- Remarks on result:
- other: overall no effects on reproductive performance
- Critical effects observed:
- not specified
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - No abnormal clinical signs were observed in offspring.
3. no effects observed - There was no difference in the general condition of pups, no abnormality was found in any group. - Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- 2. no mortality observed - No effect on numbers of live offspring of were observed as compared to control.
3. no mortality observed - There were no cases where all children died during the nursing period. There was no significant difference between the group and the vehicle control group. The number of survivors at 4 days after birth and the 4 days survival rate of neonates were significant between each treatment group and vehicle control group. - Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - No significant change in body weights of offspring were observe as compared to control.
3. no effects observed - 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:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - No gross pathological changes were observed in offsprings.
3. no effects observed - No abnormal cases were found in any group. - Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Remarks:
- 2
- Generation:
- F1
- Effect level:
- 1 000 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- clinical signs
- mortality
- body weight and weight gain
- gross pathology
- Remarks on result:
- other: No effect observed
- Dose descriptor:
- NOAEL
- Remarks:
- 3
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- clinical signs
- body weight and weight gain
- gross pathology
- Remarks on result:
- other: overall no effects on developmental parameters was observed
- Critical effects observed:
- not specified
- Reproductive effects observed:
- not specified
- Conclusions:
- Based on the data available from different studies, the No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day for reproductive toxicity, when rodents were treated with test material orally by gavage. Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.
- Executive summary:
Data available from different studies were reviewed to determine the reproductive toxicity of test chemical. The studies are as mentioned below:
In a Combined Repeat Dose and Reproductive / Developmental Toxicity Screening Test, Crj:CD(SD) male and female rats were treated with test material in the concentration of 0 (vehicle), 100, 300, 1000 mg/kg orally by gavage for 42 to 47 days according to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test). No effect on survival of treated male and female rat was observed as compared to control. Red feces exhibiting the same color tone as the test substance administered in all sexes were observed daily from the day following the administration start date. At 1000 mg/kg bw, in 2 male loose stools were observed transiently on 22 days after the start of administration, but abnormalities in general conditions considered to be toxic changes. No significant effect on body weight and body weight gain and food consumption of treated male and female rats were observed as compared to control. Significant decrease in prothrombin time were observed in male rats at 100 mg / kg/day, but no change was observed in the 300 and 1000 mg / kg group, so it was judged to be an accidental change. In females, there was no significant difference between the test substances administered group and the control group. Significant increase in A / G ratio were observed in male rats at 1000 mg / kg/day. However, since the total protein and albumin were not changed and were slightly high, it was considered to be fluctuating within the physiological range and it was judged that it was not caused by administration of the test substance. Significant increase in ASAT (GOT) in female rats at 100 mg / kg/day, but no change was observed in the 300 and 1000 mg / kg group, so it was judged to be an accidental change. Similarly, No effect on reproductive parameters such as sexual cycle, mating index, the fertility index, numbers of corpora lutea or implantations, the implantation index, the delivery index, the gestation index, gestation length, parturition or maternal behavior, numbers of offspring or live offspring of treated rats as compared to control. Significant increase in relative liver weight in male and absolute and relative weight in female were observed at 1000 mg / kg bw as compared to control. Significant decrease in absolute spleen weight and significant increase in relative adrenal gland weight were observed at 300 mg / kg bw in male rats. Significant increase in relative adrenal gland weight were observed in male rats at 100 mg / kg bw. But, since there was no change in the 1000 mg / kg group, it was judged to be an accidental change. Colored stomach at 1000 mg / kg and red, colored contents were observed in small intestine and large intestine at 100 mg / kg. Focal bleeding of the lung, contraction failure and white spots, stomach tar-like contents, white spots of the liver, dilation of the renal pelvic cavity, uterine bloating, vaginal distension and ventricular dilation were observed. However, since there was no certain tendency in its expression status, it was judged to be an accidental change unrelated to administration of the test substance. No histopathological changes were observed in treated male and female rats as compared to control. In addition, No effect on numbers of live offspring, clinical signs and body weight of offspring were observed as compared to control. No gross pathological changes were observed in offspring. Therefore, NOAEL was considered to be 1000 mg/kg/day for P and F1 generation when Crj:CD (SD) male and female rats treated with test material orally by gavage for 42 to 47 days.
In another study, combined repeated dose and reproduction / developmental screening test was performed to evaluate the toxic nature of the given test chemical according to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test). Male and female Crl:CD (SD) were used in the study. The test compound was dissolved in water and used at dose levels of 0, 40, 200 or 1000 mg/Kg/day. The male rats were treated for 42 days and female rats were treated for 41-47 days. Recovery group of 0 and 1000 mg/Kg/day was also included in the study. The treated animals were noted for clinical signs, body weight, food consumption, urinalysis, hematology, blood chemistry, organ weight changes and histopathology reproductive and developmental parameters. No mortality observed. No evidence of toxicity attributable to the test substance in all test items for both sexes was observed. In the 200 mg / kg group, female weight at birth was significantly higher than that in the vehicle control group. Female weight at birth day in 40 and 1000 mg / kg groups, male weight at birth day in each treatment group and 4 days after birth, there was no significant difference in male and female body weight between the vehicle control groups. In the measurement of food intake during the administration period, vehicle control was performed on day 29 in the 40 and 200 mg / kg administration groups. A significantly lower value was found compared to the group for males. During the recovery period, No significant difference was found between the 1000 mg / kg group and the vehicle control recovery group. Before mating, during pregnancy and during the lactation period of the mother animal, each administration group is compared with the vehicle control group. There was no significant difference between them. Between the 1000 mg / kg dose group and the vehicle control recovery group in the recovery group that did not carry out mating. There was no significant difference. In the male 1000 mg / kg dose group, significant low values of AST and glucose. A significant increase in glucose was noted in the female 1000 mg / kg group. Also, in the female 1000 mg / kg group, hematological examination showed a significant increase in eosinophil ratio. Both male and female, each administration at the end of the administration period and at the end of the recovery period, there was no significant difference between the group and the vehicle control group was observed in urinalysis. In histopathological examination, calcification of the pulmonary artery, hepatocellular necrosis in the liver, small granuloma in the liver, kidney, visceral cyst formation, adrenal cortical vacuolation and intrastromal lymphocyte infiltration of the prostate were found in a few cases. In addition,histopathological changes observed in the histopathological examination of males in the 1000 mg / kg dose group. Pregnancy lupus number, implantation rate, birth rate, gestational age, parturition status and lactation status are increased by test substance administration. The number of implantations in the 1000 mg / kg dose group compared to the vehicle control group. There was a significant increase in the number of pregnant women, but the number of pregnant corpus corpora lutea and implantation rate differed between each treatment group and vehicle control group. Because there was no significant difference between the two, it is considered to be a change that has no toxicological significance. There was no difference in the general condition of pups, no abnormality was found in any group. There were no cases where all children died during the nursing period. There was no significant difference between the group and the vehicle control group. The number of survivors at 4 days after birth and the 4 days survival rate of neonates were significant between each treatment group and vehicle control group. No abnormal cases were found in any group. Hence, the No Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity is considered to be 1000 mg/Kg/day, when male and female Crl:CD (SD) were treated with the given test chemical orally.
Based on the data available from different studies, NOAEL was considered to be 1000 mg/kg/day for reproductive toxicity, when rodents were treated with test material orally. Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from handbook or collection of data.
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
Data available from different studies were reviewed to determine the reproductive toxicity of test chemical. The studies are as mentioned below:
In a Combined Repeat Dose and Reproductive / Developmental Toxicity Screening Test, Crj:CD(SD) male and female rats were treated with test material in the concentration of 0 (vehicle), 100, 300, 1000 mg/kg orally by gavage for 42 to 47 days according to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test). No effect on survival of treated male and female rat was observed as compared to control. Red feces exhibiting the same color tone as the test substance administered in all sexes were observed daily from the day following the administration start date. At 1000 mg/kg bw, in 2 male loose stools were observed transiently on 22 days after the start of administration, but abnormalities in general conditions considered to be toxic changes. No significant effect on body weight and body weight gain and food consumption of treated male and female rats were observed as compared to control. Significant decrease in prothrombin time were observed in male rats at 100 mg / kg/day, but no change was observed in the 300 and 1000 mg / kg group, so it was judged to be an accidental change. In females, there was no significant difference between the test substances administered group and the control group. Significant increase in A / G ratio were observed in male rats at 1000 mg / kg/day. However, since the total protein and albumin were not changed and were slightly high, it was considered to be fluctuating within the physiological range and it was judged that it was not caused by administration of the test substance. Significant increase in ASAT (GOT) in female rats at 100 mg / kg/day, but no change was observed in the 300 and 1000 mg / kg group, so it was judged to be an accidental change. Similarly, No effect on reproductive parameters such as sexual cycle, mating index, the fertility index, numbers of corpora lutea or implantations, the implantation index, the delivery index, the gestation index, gestation length, parturition or maternal behavior, numbers of offspring or live offspring of treated rats as compared to control. Significant increase in relative liver weight in male and absolute and relative weight in female were observed at 1000 mg / kg bw as compared to control. Significant decrease in absolute spleen weight and significant increase in relative adrenal gland weight were observed at 300 mg / kg bw in male rats. Significant increase in relative adrenal gland weight were observed in male rats at 100 mg / kg bw. But, since there was no change in the 1000 mg / kg group, it was judged to be an accidental change. Colored stomach at 1000 mg / kg and red, colored contents were observed in small intestine and large intestine at 100 mg / kg. Focal bleeding of the lung, contraction failure and white spots, stomach tar-like contents, white spots of the liver, dilation of the renal pelvic cavity, uterine bloating, vaginal distension and ventricular dilation were observed. However, since there was no certain tendency in its expression status, it was judged to be an accidental change unrelated to administration of the test substance. No histopathological changes were observed in treated male and female rats as compared to control. In addition, No effect on numbers of live offspring, clinical signs and body weight of offspring were observed as compared to control. No gross pathological changes were observed in offspring. Therefore, NOAEL was considered to be 1000 mg/kg/day for P and F1 generation when Crj:CD (SD) male and female rats treated with test material orally by gavage for 42 to 47 days.
In another study, combined repeated dose and reproduction / developmental screening test was performed to evaluate the toxic nature of the given test chemical according to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test). Male and female Crl:CD (SD) were used in the study. The test compound was dissolved in water and used at dose levels of 0, 40, 200 or 1000 mg/Kg/day. The male rats were treated for 42 days and female rats were treated for 41-47 days. Recovery group of 0 and 1000 mg/Kg/day was also included in the study. The treated animals were noted for clinical signs, body weight, food consumption, urinalysis, hematology, blood chemistry, organ weight changes and histopathology reproductive and developmental parameters. No mortality observed. No evidence of toxicity attributable to the test substance in all test items for both sexes was observed. In the 200 mg / kg group, female weight at birth was significantly higher than that in the vehicle control group. Female weight at birth day in 40 and 1000 mg / kg groups, male weight at birth day in each treatment group and 4 days after birth, there was no significant difference in male and female body weight between the vehicle control groups. In the measurement of food intake during the administration period, vehicle control was performed on day 29 in the 40 and 200 mg / kg administration groups. A significantly lower value was found compared to the group for males. During the recovery period, No significant difference was found between the 1000 mg / kg group and the vehicle control recovery group. Before mating, during pregnancy and during the lactation period of the mother animal, each administration group is compared with the vehicle control group. There was no significant difference between them. Between the 1000 mg / kg dose group and the vehicle control recovery group in the recovery group that did not carry out mating. There was no significant difference. In the male 1000 mg / kg dose group, significant low values of AST and glucose. A significant increase in glucose was noted in the female 1000 mg / kg group. Also, in the female 1000 mg / kg group, hematological examination showed a significant increase in eosinophil ratio. Both male and female, each administration at the end of the administration period and at the end of the recovery period, there was no significant difference between the group and the vehicle control group was observed in urinalysis. In histopathological examination, calcification of the pulmonary artery, hepatocellular necrosis in the liver, small granuloma in the liver, kidney, visceral cyst formation, adrenal cortical vacuolation and intrastromal lymphocyte infiltration of the prostate were found in a few cases. In addition,histopathological changes observed in the histopathological examination of males in the 1000 mg / kg dose group. Pregnancy lupus number, implantation rate, birth rate, gestational age, parturition status and lactation status are increased by test substance administration. The number of implantations in the 1000 mg / kg dose group compared to the vehicle control group. There was a significant increase in the number of pregnant women, but the number of pregnant corpus corpora lutea and implantation rate differed between each treatment group and vehicle control group. Because there was no significant difference between the two, it is considered to be a change that has no toxicological significance. There was no difference in the general condition of pups, no abnormality was found in any group. There were no cases where all children died during the nursing period. There was no significant difference between the group and the vehicle control group. The number of survivors at 4 days after birth and the 4 days survival rate of neonates were significant between each treatment group and vehicle control group. No abnormal cases were found in any group. Hence, the No Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity is considered to be 1000 mg/Kg/day, when male and female Crl:CD (SD) were treated with the given test chemical orally.
Based on the data available from different studies, NOAEL was considered to be 1000 mg/kg/day for reproductive toxicity, when rodents were treated with test material orally. Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
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
Comparing the NOAEL value and effects observed on rodents, with the criteria of CLP regulation the given test chemical is not likely to classify as reproductive toxicant.
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