Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 209-502-6 | CAS number: 583-39-1
- 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:
- concentration-driven
Effects on fertility
Description of key information
Reproductive toxicity study
Based on the data available from different studies, NOAEL for test chemical was considered to be 30 mg/kg /day for reproductive toxicity, when male and female rats were treated with test material orally. Thus, comparing this value with the criteria of CLP regulation test chemical is not likely to classify as reproductive toxicant.
Link to relevant study records
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- 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 peer- reviewed journal
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- The adverse effects of test chemical on pregnant Wistar rats were examined.
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- not specified
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- not specified
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: CLEA Japan Inc. (Tokyo, Japan)
- Age at study initiation: Four-week-old
- Housing: Housed individually in stainless steel cages
- Diet (e.g. ad libitum): Feed (NMF, Oriental Yeast Co., Ltd., Tokyo, Japan) ; ad libitum
- Water (e.g. ad libitum): Tap water; ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C
- Humidity (%):60 ± 10%
- Photoperiod (hrs dark / hrs light): Dark period from 7:00 PM to 7:00 AM - Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on exposure:
- not specified
- Details on mating procedure:
- - Impregnation procedure: [artificial insemination / purchased timed pregnant / cohoused]: cohoused
- If cohoused:
- M/F ratio per cage: females were individually paired overnight with a male of similar age.
- Length of cohabitation: overnight
- Further matings after two unsuccessful attempts: no
- Verification of same strain and source of both sexes: no
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: The day upon which sperm was found in vaginal smears was designated as Day 0 of gestation. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 11 days
- Frequency of treatment:
- Daily
- Details on study schedule:
- 20 days of gestation
- Remarks:
- 0,2.5,5,10,20,40 and 60 mg/kg bw for dose finding study
- Remarks:
- 0.3.3,10,30 mg/kg bw for teratogenicity study
- No. of animals per sex per dose:
- Dose-finding study:
Mated (pregnant) rats were assigned to seven groups of five or six animals each.
Teratology study:
Mated (pregnant) rats were divided into four groups of 20 rats each. - Control animals:
- yes
- Details on study design:
- Dose-finding study:
Mated rats were assigned to seven groups of five or six animals each. They were treated by gavage with 2-MBI in oIive oil at 0, 2.5, 5, 10, 20, 40, and 60 mg/kg/day in a volume of 5 ml/kg from Days 7 through 17 of gestation. The animals were weighed and food consumpiion was measured each day; general condition and behavior were also observed. On Day 20 of gestation, the animaIs were killed under diethylether anesthesia, laparotomy was performed, and the maternal thymus and the gravid uterus were weighed. The position and number of live and dead fetuses, including resorbed fetuses, and the number of corpora lutea were recorded. Live fetuses were weighed, sexed, and gross deformities noted. Only one dam treated with 60 mg/kg of test chemical survived; viscera ot the fetuses were examined.
Teratology study:
Dose levels of 0, 3.3, 10, and 30 mg/kg/day in a volume of 5 ml/kg were selected based upon the results of the dose-finding study.
The dose-finding study revealed that 60 mg/kg was toxic to both fetuses and dams when given throughout the period of organogenesis (Days 7-17 of gestation).Therefo re, when mated (pregnant) rats were dosed with 60 mg/kg of test chemical it was given upon 3 or 4 consecutive days at different periods during organogenesis (Days 7— 10, 11 —14, and I 5—17 of gestation). The other procedures were the same as described here. - Positive control:
- not specified
- Parental animals: Observations and examinations:
- BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
OTHER:
GENERAL CONDITION AND BEHAVIOUR: Yes
ORGAN WEIGHT:
Maternal thymus, thyroid gland, and gravid uterus were weighed. - Oestrous cyclicity (parental animals):
- The uterine content was examined after termination: Yes
Examinations included:
- Number of early resorptions: Yes
- Number of corpora lutea were recorded. - Sperm parameters (parental animals):
- not specified
- Litter observations:
- The position and number of live and dead fetuses, including resorbed fetuses were recorded. Live fetuses were weighed, sexed, and gross deformities noted.
- Postmortem examinations (parental animals):
- GROSS NECROPSY
- Uteri was examined grossly. - Postmortem examinations (offspring):
- GROSS NECROPSY
- Fetuses were examined grossly.
- Gross necropsy consisted of Visceral and Skeletal observation. - Statistics:
- Data from the dose-finding and teratology studies in which animals were treated with ≤30 mg/kg of test chemical were analyzed by Dunnett’s multiple comparison method in a parametric or nonpararnetric manner.
- Reproductive indices:
- not specified
- Offspring viability indices:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- 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:
- effects observed, treatment-related
- 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:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 30 < mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- mortality
- body weight and weight gain
- food consumption and compound intake
- reproductive performance
- Remarks on result:
- other: No effects on reproductive performance
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- Live fetuses was observed.
- Body weight and weight changes:
- effects observed, treatment-related
- 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:
- effects observed, treatment-related
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 30 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- viability
- mortality
- body weight and weight gain
- gross pathology
- other: No adverse effects observed on
- Remarks on result:
- other: Fetal body weights significantly decreased only in the litters of dams dosed with 10 mg/kg or higher dose
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Conclusions:
- NOAEL was considered to be 30 mg/kg bw when Wistar female rat were treated with test chemical orally by gavage from day 7 to 17.
- Executive summary:
In a reproductive toxicity study, Wistar female rat were treated with test chemical in the concentration of 0,2.5,5,10,20,40 and 60 mg/kg bw for dose finding study and 0.3.3,10,30 mg/kg bw for teratogenicity study orally by gavage in olive oil from day 7 to 17. Four of five rats treated with 60 mg/kg of test chemical and one of six rats treated with 40 mg/kg died in Dose-finding study and all dams survived in main study. The maternal weight gain was decreased at a 40 and a 20 mg/kg of test chemical respectively in dose-finding study Substantial decrease in body weight gain was observed in all three groups in Teratology study. Food consumption was decreased at a 40 and a 20 mg/kg of test chemical , respectively in dose-finding study and Substantial decrease in food consumption was observed in all three groups in teratology study. Thymus weight was decreased even at the lowest dose of 3.3 mg/kg whereas treatment with 10 and 30 mg/kg of test chemical resulted in increased thyroid weight. No effete on reproduction of treated female rats were observed as compared to control. In addition,All fetuses from dams treated with daily doses upto 40 mg/kg body weight, all parameters with respect to fetuses were unaffected in Dose-finding study. Only rudimentary lumbar ribs were observed when the treatment period with 60 mg/kg was shortened to Gestation days 7-10, while kinked ureter and dialated renal pelvis were observed only following treatment with 60 mg/kg on days 15-17. Finally, dilated lateral ventricles and cleft palate were observed only in the litters f dams treated with 60 mg/kg on Days 11-14; these anomalies were not observed at lower doses of the chemical. Significantly decreased only in the litters of dams dosed with 10 mg/kg or higher of test chemical . Visceral variations consisting of unilateral or bilateral kinked ureter and / or dilated renal pelvis were noted in 20.5% of fetuses at 10 mg/kg and in 47.6% of the fetuses at 30 mg/kg. Skeletal variations, unilateral or bilateral rudimentary lumbar ribs, were observed in 22.2% of the fetuses at 30 mg/kg were observed. The degree of ossification was significantly reduced in the litters of dams treated with ≥ 10 mg/kg of test chemical in main study. Therefore, NOAEL was considered to be 30 mg/kg bw when Wistar female rat were treated with test chemical orally by gavage from day 7 to 17.
Reference
Teratology study: All dams survived.
Dose-finding study: Four of five rats treated with 60 mg/kg dose and one of six rats treated with 40 mg/kg died.
Body weight:
Teratology study: Substantial decrease in body weight gain was observed in all three groups.
Dose-finding study: In pregnant rats, the maternal weight gain was decreased at a 40 and a 20 mg/kg of test chemical , respectively.
Food consumption:
Teratology study: Substantial decrease in food consumption was observed in all three groups.
Dose-finding study: In pregnant rats, the food consumption was decreased at a 40 and a 20 mg/kg of test chemical , respectively.
Organ weight: Thymus weight was decreased even at the lowest dose of 3.3 mg/kg whereas treatment with 10 and 30 mg/kg of test chemical resulted in increased thyroid weight.
Reproductive performance:
No effects on reproduction of treated female rats were observed
Fetal body weights significantly decreased only in the litters of dams dosed with 10 mg/kg or higher dose
Gross pathology:
Visceral variations consisting of unilateral or bilateral kinked ureter and / or dilated renal pelvis were noted in 20.5% of fetuses at 10 mg/kg and in 47.6% of the fetuses at 30 mg/kg.
Skeletal variations, unilateral or bilateral rudimentary lumbar ribs, were observed in 22.2% of the fetuses at 30 mg/kg.
The degree of ossification was significantly reduced in the litters of dams treated with ≥ 10 mg/kg of test chemical
Dose-finding study
All fetuses from dams treated with daily doses upto 40 mg/kg body weight, all parameters with respect to fetuses were unaffected.
Only rudimentary lumbar ribs were observed when the treatment period with 60 mg/kg was shortened to Gestation days 7-10, while kinked ureter and dialated renal pelvis were observed only following treatment with 60 mg/kg on days 15-17. Finally , dilated lateral ventricles and cleft palate were observed only in the litters f dams treated with 60 mg/kg on Days 11-14; these anomalies were not observed at lower doses of the chemical.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 30 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from authoritative database
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Reproductive toxicity study
Data available from different studies were reviewed to determine the reproductive toxicity of test chemical.The studies are as mentioned below:
Study 1
In a reproductive toxicity study, Wistar female rat were treated with test chemical in the concentration of 0,2.5,5,10,20,40 and 60 mg/kg bw for dose finding study and 0.3.3,10,30 mg/kg bw for teratogenicity study orally by gavage in olive oil from day 7 to 17. Four of five rats treated with 60 mg/kg of test chemical and one of six rats treated with 40 mg/kg died in Dose-finding study and all dams survived in main study. The maternal weight gain was decreased at a 40 and a 20 mg/kg of test chemical respectively in dose-finding study Substantial decrease in body weight gain was observed in all three groups in Teratology study. Food consumption was decreased at a 40 and a 20 mg/kg of test chemical , respectively in dose-finding study and Substantial decrease in food consumption was observed in all three groups in teratology study. Thymus weight was decreased even at the lowest dose of 3.3 mg/kg whereas treatment with 10 and 30 mg/kg of test chemical resulted in increased thyroid weight. No effete on reproduction of treated female rats were observed as compared to control. In addition,All fetuses from dams treated with daily doses upto 40 mg/kg body weight, all parameters with respect to fetuses were unaffected in Dose-finding study. Only rudimentary lumbar ribs were observed when the treatment period with 60 mg/kg was shortened to Gestation days 7-10, while kinked ureter and dialated renal pelvis were observed only following treatment with 60 mg/kg on days 15-17. Finally, dilated lateral ventricles and cleft palate were observed only in the litters f dams treated with 60 mg/kg on Days 11-14; these anomalies were not observed at lower doses of the chemical. Significantly decreased only in the litters of dams dosed with 10 mg/kg or higher of test chemical . Visceral variations consisting of unilateral or bilateral kinked ureter and / or dilated renal pelvis were noted in 20.5% of fetuses at 10 mg/kg and in 47.6% of the fetuses at 30 mg/kg. Skeletal variations, unilateral or bilateral rudimentary lumbar ribs, were observed in 22.2% of the fetuses at 30 mg/kg were observed. The degree of ossification was significantly reduced in the litters of dams treated with ≥ 10 mg/kg of test chemical in main study. Therefore, NOAEL was considered to be 30 mg/kg bw when Wistar female rat were treated with test chemical orally by gavage from day 7 to 17.
Study 2
The sperm morphology and vaginal cytology examinations (SMVCEs) study, Fischer 344 male rats were treated with test chemical in the concentration of 0, 1.0, 3.0 and 10 mg/m3by inhalation. No effects on body weight were observed in treated male rat. In addition, Male rats exhibited no change in testicular weight or epididymal weight and no significantly effect on sperm mortality. Therefore, NOAEL was considered to be 10 mg/m3when Fischer 344 male rats were treated with test chemical by inhalation for 13 weeks.
Effects on developmental toxicity
Description of key information
Developmental toxicity study
Based on the various studies available for the test chemical were reviewed to determine the developmental toxicity, NOAELfor test chemical was considered to be 30 mg /kg bw/day .When rats were treated with test chemical orally. Thus, comparing this value with the criteria of CLP regulation test chemical is not likely to classify as reproductive and developmental toxicant.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data from peer reviewed journal
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- The adverse effects of test chemical on pregnant Wistar rats and their fetuses were examined.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: CLEA Japan Inc. (Tokyo, Japan)
- Age at study initiation: Four-week-old
- Housing: Housed individually in stainless steel cages
- Diet (e.g. ad libitum): Feed (NMF, Oriental Yeast Co., Ltd., Tokyo, Japan) ; ad libitum
- Water (e.g. ad libitum): Tap water; ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C
- Humidity (%):60 ± 10%
- Photoperiod (hrs dark / hrs light): Dark period from 7:00 PM to 7:00 AM - Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: Cohoused
- If cohoused:
- M/F ratio per cage: females were individually paired overnight with a male of similar age.
- Length of cohabitation: overnight
- Further matings after two unsuccessful attempts: no
- Verification of same strain and source of both sexes: [yes / no (explain)]: no
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: The day upon which sperm was found in vaginal smears was designated as Day 0 of gestation. - Duration of treatment / exposure:
- 7-17 days
- Frequency of treatment:
- Daily
- Duration of test:
- 20 days of gestation
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Control group (Dose-finding study)
- Dose / conc.:
- 2.5 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 5 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 10 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 20 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 40 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 60 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Control group (Teratology study)
- Dose / conc.:
- 3.3 mg/kg bw/day
- Remarks:
- Teratology study
- Dose / conc.:
- 10 mg/kg bw/day
- Remarks:
- Teratology study
- Dose / conc.:
- 30 mg/kg bw/day
- Remarks:
- Teratology study
- No. of animals per sex per dose:
- Dose-finding study:
Mated (pregnant) rats were assigned to seven groups of five or six animals each.
Teratology study:
Mated (pregnant) rats were divided into four groups of 20 rats each. - Control animals:
- yes
- Details on study design:
- Dose-finding study:
Mated rats were assigned to seven groups of five or six animals each. They were treated by gavage with 2-MBI in oIive oil at 0, 2.5, 5, 10, 20, 40, and 60 mg/kg/day in a volume of 5 ml/kg from Days 7 through 17 of gestation. The animals were weighed and food consumpiion was measured each day; general condition and behavior were also observed. On Day 20 of gestation, the animaIs were killed under diet hylether anesthesia, laparotomy was performed, and the maternal thymus and the gravid uterus were weighed. The position and number of live and dead fetuses, including resorbed fetuses, and the number of corpora lutea were recorded. Live fetuses were weighed, sexed, and gross deformities noted. Only one dam treated with 60 mg/kg of 2-MBI survived; viscera ot the fetuses were examined.
Teratology study:
Dose levels of 0, 3.3, 10, and 30 mg/kg/day in a volume of 5 ml/kg were selected based upon the results of the dose-finding study.The dose-finding study revealed that 60 mg/kg was toxic to both fetuses and dams when given throughout the period of organogenesis (Days 7-17 of gestation).Therefore, when mated (pregnant) rats
were dosed with 60 mg/kg of 2-MBI, it was given upon 3 or 4 consecutive days at different periods during organogenesis (Days 7— 10, 11 —14, and I 5—17 of gestation). The other procedures were the same as described here. - Maternal examinations:
- BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
OTHER:
GENERAL CONDITION AND BEHAVIOUR: Yes
ORGAN WEIGHT:
Maternal thymus, thyroid gland, and gravid uterus were weighed. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of early resorptions: Yes - Fetal examinations:
- - Fetuses were examined grossly.
- Gross necropsy consisted of Visceral and Skeletal observation.
- The position and number of live and dead fetuses, including resorbed fetuses were recorded. Live fetuses were weighed, sexed, and gross deformities noted. - Statistics:
- Data from the dose-finding and teratology studies in which animals were treated with ≤30 mg/kg of test chemical were analyzed by Dunnett’s multiple comparison method in a parametric or nonpararnetric manner.
- Indices:
- not specified
- Historical control data:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Teratology study
All dams treated with 0, 3.3, 10 and 30 mg/kg of test chemical survived.
Dose-finding sludy
Four of five rats treated with 60 mg/kg of test chemical and one of 6 rats treated with 40 mg/kg died. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Teratology study
Substantial decrease in body weight gain was observed in all three groups.
Dose-finding sludy
In pregnant rats, the maternal weight gain was decreased at a 40 and a 20 mg/kg of test chemical espectively. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Teratology study
Substantial decrease in food consumption was observed in all three groups.
Dose-finding sludy
In pregnant rats, the food consumption was decreased at a 40 and a 20 mg/kg of test chemical , respectively. - 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:
- effects observed, treatment-related
- Description (incidence and severity):
- Thymus weight was decreased even at the lowest dose of 3.3 mg/kg whereas treatment with 10 and 30 mg/kg of test chemical resulted in increased thyroid weight.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- 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:yes
Details on maternal toxic effects:
Decreased thymus weights, increased thyroid weights, decreased body weight gain, and decreased food consumption in the treated dams were observed.Because of the severe resulting toxicity, 60 mg/kg dose could not be administered throughout the period of organogenesis (Gestetion days 7-17). Instead, the test animals were dosed for shorter periods of time, viz., Gestation Days 7-10 (17 rats), 11-14 (16 pregnant rats), or 15-17(16 pregnant rats). Even under these dosing conditions, test chemical was severely toxic to dams, as evidenced by a substantial decrease in maternal body weight gain and food consumption in all three groups and maternal death (5 out of 16 dams) in the group treated on Days 11-14 of gestation. Vaginal bleeding was observed in 10 and 2 dams in the group treated on Days 11-14 and 15-17 of gestation, respectively. - Dose descriptor:
- NOAEL
- Effect level:
- < 3.3 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: Because of significant decrease in maternal thymus weights at this dose.
- Abnormalities:
- not specified
- Localisation:
- not specified
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Fetal body weights were significantly decreased only in the litters of dams dosed with 10 mg/kg or higher dose of test chemical
- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- not specified
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Skeletal variations, unilateral or bilateral rudimentary lumbar ribs, were observed in 22.2% of the fetuses at 30 mg/kg.
The degree of ossification was significantly reduced in the litters of dams treated with ≥ 10 mg/kg of test chemical - Visceral malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Visceral variations consisting of unilateral or bilateral kinked ureter and / or dilated renal pelvis were noted in 20.5% of fetuses at 10 mg/kg and in 47.6% of the fetuses at 30 mg/kg.
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Decresed fetal body weights and increased the incidence of certain anomalies of the urogenital system and of rudimentary lumbar ribs.
Dose-finding study
All fetuses from dams treated with daily doses upto 40 mg/kg body weight, all parameters with respect to fetuses were unaffected.
Only rudimentary lumbar ribs were observed when the treatment period with 60 mg/kg was shortened to Gestation days 7-10, while kinked ureter and dialated renal pelvis were observed only following treatment with 60 mg/kg on days 15-17. Finally , dilated lateral ventricles and cleft palate were observed only in the
litters of dams treated with 60 mg/kg on Days 11-14; these anomalies were not observed at lower doses of the chemical. - Dose descriptor:
- NOAEL
- Effect level:
- 3.3 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: teratogenicity
- Remarks on result:
- other: No developmental toxic effects were observed
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- The no observed adverse effect level was considered to be 3.3 mg/kg. When rats were treated with test chemical orally.
- Executive summary:
The study was designed to investigate the reproductive toxicity effects of test chemical to pregnant Wistar rats and to their fetuses by oral route. Pregnant rats were treated with test chemical at doses of 0, 3.3, 10, and 30 mg/kg during the period of organogenesis (Gestation Days 7-17). Mated (pregnant) rats were divided into four groups of 20 rats each. Treatment with 10 and 30 mg/kg of test chemical resulted in decreased thymus weights, increased thyroid weights, decreased body weight gain, and decreased food consumption in the treated dams. These dosages also reduced fetal body weights and increased the incidence of certain anomalies of the urogenital system and of rudimentry lumbar ribs. Under the conditions of the present study, The no observed adverse effect level was considered to be 3.3 mg/kg. When rats were treated with test chemical orally.
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 30 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from authoritative database
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Developmental toxicity study
Data available from different studies for test chemicals were reviewed to determine the developmental toxicity of test chemical. The studies are as mentioned below:
Study 1
The study was designed to investigate the reproductive toxicity effects of test chemical to pregnant Wistar rats and to their fetuses by oral route. Pregnant rats were treated with test chemical at doses of 0, 3.3, 10, and 30 mg/kg during the period of organogenesis (Gestation Days 7-17). Mated (pregnant) rats were divided into four groups of 20 rats each. Treatment with 10 and 30 mg/kg of test chemical resulted in decreased thymus weights, increased thyroid weights, decreased body weight gain, and decreased food consumption in the treated dams. These dosages also reduced fetal body weights and increased the incidence of certain anomalies of the urogenital system and of rudimentry lumbar ribs. Under the conditions of the present study, The no observed adverse effect level was considered to be 3.3 mg/kg. When rats were treated with test chemical orally.
Study 2
In order to investigate teratogenic potential of test chemical, the female wistar rats were given a single dosage of 120 mg/kg of the test chemica orally by stomach intubation on day 12 or 13 (because higher dosages killed some pregnant females). Females were killed on day 22 of gestation and individual litter weight, litter size, and number of deciduomas and corpora lutea determined. Approximately two thirds of the fetuses were processed for skeleton examination and the remainder for visceral examination. Thetest chemical did not displayed any teratogenic potential at the maternally tolerated dosages (120 mg/kg). All anomalies in fetuses to test chemical were minor, such as nonfusion of 5th sternebra, wavy ribs, retarded ossification, and 14th rib. Thus, under the conditions of the present study, the no observed adverse effect level (NOAEL) of test chemical for teratogenicity was considered to be 120 mg/kg.
Justification for classification or non-classification
Thus, comparing this value with the criteria of CLP regulation test chemical is not likely to classify as reproductive and developmental toxicant.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.