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EC number: 204-508-5 | CAS number: 121-92-6
- 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 material was considered to be 100 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 material 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:
- 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 J check
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Principles of method if other than guideline:
- Combined repeated dose reproduction / developmental toxicity Screen of test chemical was performed in rats orally
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- Data is from J check
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data available
- Age at study initiation: 9 weeks old (initiation of dosing)
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available - Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- other: 0.1w/v% Tween 80 + 0.5w/v% Sodium carboxymethylcellulose solution
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Test chemical was dissolved in 0.1 w/v% Tween 80 + 0.5 w/v% Sodium carboxymethylcellulose solution at dose levels of 0, 20, 100 or 500 mg/Kg bw/day
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): 0.1 w/v% Tween 80 + 0.5 w/v% Sodium carboxymethylcellulose solution
- Concentration in vehicle: 0, 20, 100 or 500 mg/kg bw/day
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 42 days
- Frequency of treatment:
- Daily
- Details on study schedule:
- No data available
- Remarks:
- Doses / Concentrations:
0, 20, 100 or 500 mg/kg/day
Basis:
no data - No. of animals per sex per dose:
- Total: 116
0 mg/kg/day: 12 male, 12 female
20 mg/kg/day: 12 male, 12 female
100 mg/kg/day: 12 male, 12 female
500 mg/kg/day: 12 male, 12 female
Recovery:
0 mg/kg/day: 5 male, 5 female
500 mg/kg/day: 5 male, 5 female
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. Mortality were observed
DETAILED CLINICAL OBSERVATIONS: Yes, animal were observed for salivation
- Time schedule: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: Observed during dosing period
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight : No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:
No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. Red blood cell count, hemoglobin concentration and hematocrit value were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. A/G ratio, Pi, K, BUN, TP, Cl and ALT were examined.
OTHER:
Organ weight: Brain R, Liver R, Kidney R, Testes A/R, Epididymides A/R, Thymus A and Spleen A/R were weighed. - Oestrous cyclicity (parental animals):
- Any irregularities in the estrous cycle were investigated.
- Sperm parameters (parental animals):
- No data
- Litter observations:
- Number of live offspring, clinical signs and body weight were observed.
- Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: No detailed data available
- Maternal animals: No data available
GROSS NECROPSY and HISTOPATHOLOGY / ORGAN WEIGHTS
The target organs for the study were Stomach, Bone, Testes, Epididymides, (Female genital tract) - Postmortem examinations (offspring):
- No detailed data available
- Statistics:
- No data
- Reproductive indices:
- Gestation index, delivery index, number of corpora lutea, number of implantations, implantation index and number of offspring delivered were observed
- Offspring viability indices:
- Offspring viability on day 0 and 4 were observed
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Salivation was observed in 500 mg/kg bw/day treated male and female rats as compared to control and and decrease in locomotor activity, irregular respiration, prone position and drastic worsening was observed in female rat.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- When treated with 500 mg/kg bw/day, three female rats died as compared to control.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Restrained body weight gain was observed in 500 mg/kg bw/day treated male rat as compared to control.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- On day 8, Decrease in the food consumption was observed in 500 mg/kg bw/day treated male and female rat as compared to control.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No effects was observed in treated male and female rat as compared to control.
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- In male rat, Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium of testes, Decrease sperm in the epididymides duct, Cell debris in epididymides duct and Increase in the trabecular bone in femur bone were observed in 500 mg/kg bw/day during treatment and recovery.
In female rat, Squamous hyperplasia and Erosion in forestomach during test and Increase in trabecular bone in femur bone during test and Recovery at in 500 mg/kg bw/day treated female rats. - Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- No effects were observed on estrous cycle, irregular estrous cycle, mating index, mating days until copulation, number of estrous stages without mating.
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- No effects were observed on estrous cycle, irregular estrous cycle, mating index, mating days until copulation, number of estrous stages without mating, fertility index, gestation period and parturition or maternal behavior of treated rat.
Reproductive performance:
Decrease in gestation index, delivery index, number of corpora lutea, number of implantation sites, implantation index and number of pups delivered were observed in 500 mg/kg bw/day treated female rats. - Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive function (oestrous cycle)
- reproductive performance
- other: Effects were observed at 500 mg/kg bw/day
- Remarks on result:
- other: effects observed at 500mg/kg bw
- Critical effects observed:
- not specified
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No effect were observed on Clinical signs of pups
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- When treated with 500 mg/kg/day, decrease in number of live pups on day 4 were observed as compared to control.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No change in body weight of pups was observed in treated rats.
- 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):
- No abnormal changes were observed in Gross pathology of pups.
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- clinical signs
- mortality
- body weight and weight gain
- gross pathology
- other: No of pups delivered. The effects were observed at 500 mg/Kg bw/day
- Remarks on result:
- other: No of pups delivered. The effects were observed at 500 mg/Kg bw/day
- Critical effects observed:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Conclusions:
- The no-observed-adverse-effect-level (NOAEL) was considered to be 100 mg/kg/day for F0 and F1 generation when Crl:CD(SD) male and female rat were treated with test chemical orally.
- Executive summary:
In Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test, Crl:CD (SD) male and female rats were treated with test chemical in the concentration of 0, 20, 100 and 500 mg/kg bw/day orally by gavage. In F0 generation, when treated with 500 mg/kg/day, three female rats died, Salivation in male and female rat was noted, restrained body weight gain in male rat and decrease in the food consumption on day 8 in male and female rat were observed. Similarly, Decrease in the RBC, Hgb and Hct level in male and female rat, Increase in A/G ratio, Pi, K and Decrease in Blood Urea Nitrogen, total protein, Cl level in male rat and Increase in ALT level in female rat were observed in 500 mg/kg/day. In addition, Increase in Relative brain, liver and kidney weight and Decrease in absolute and relative testes and epididymides weight during test and recovery and absolute thymus weight during test in male rat and Increase in relative liver and spleen weight during test and recovery and absolute spleen and kidney weight in recovery and Decrease in absolute thymus weight during test in female, Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium of testes, decrease sperm and cell debris in epididymides duct and an increase in the trabecular bone in femur bone in male rat and squamous hyperplasia and erosion in forestomach during test and an increase in trabecular bone in femur bone during test and recovery in female rat treated with 500 mg/kg/day. Decrease in gestation index, delivery index, number of corpora lutea, number of implantation sites, implantation index and number of pups delivered in F0 female and a decrease in number of pups delivered, number of live pups on day 0 and number of live pups on day 4 were observed in F1 generation treated with 500 mg/kg bw/day female rats. Based on the observations made, the reproductive No Observed Adverse Effect Level (NOAEL) was considered to be 100 mg/kg body/day for F0 and F1 generation when Crl:CD (SD) male and female rats were treated with test chemical.
Reference
When treated with 500 mg/kg bw/day, three female rats died as compared to control.
Clinical signs:
Salivation was observed in 500 mg/kg bw/day treated male and female rats as compared to control and and decrease in locomotor activity, irregular respiration, prone position and drastic worsening was observed in female rat.
Body weight and weight gain:
Restrained body weight gain was observed in 500 mg/kg bw/day treated male rat as compared to control.
Food consumption:
On day 8, Decrease in the food consumption was observed in 500 mg/kg bw/day treated male and female rat as compared to control.
Urinalysis:
No effects was observed in treated male and female rat as compared to control.
Hematology:
Decrease in the RBC, Hgb and Hct level were observed in 500 mg/kg bw/day treated male and female rat as compared to control.
Blood chemistry:
In male rats, Increase in the A/G ratio, Pi, K, and Decrease in Blood Urea Nitrogen, total protein and Cl level were observed in 500 mg/kg bw/day.
In female rats, Increase in ALT was observed in 500 mg/kg bw/day.
Organ weight:
In male rats, Increase in Relative brain, liver and kidney weight and Decrease in Absolute and Relative testes and epididymides weight during test and recovery and Absolute thymus weight during test were observed in 500 mg/kg bw/day.
In female, Increase in Relative liver and spleen weight during test and recovery and Absolute spleen and kidney weight in recovery and Decrease in Absolute thymus weight during test were observed in 500 mg/kg bw/day.
Histopathology:
In male rat, Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium of testes, Decrease sperm in the epididymides duct, Cell debris in epididymides duct and Increase in the trabecular bone in femur bone were observed in 500 mg/kg bw/day during treatment and recovery.
In female rat, Squamous hyperplasia and Erosion in forestomach during test and Increase in trabecular bone in femur bone during test and Recovery at in 500 mg/kg bw/day treated female rats.
Reproductive function:
No effects were observed on estrous cycle, irregular estrous cycle, mating index, mating days until copulation, number of estrous stages without mating, fertility index, gestation period and parturition or maternal behavior of treated rat.
Reproductive performance:
Decrease in gestation index, delivery index, number of corpora lutea, number of implantation sites, implantation index and number of pups delivered were observed in 500 mg/kg bw/day treated female rats.
Clinical signs: No effect were observed on Clinical signs of pups
Body weight: No change in body weight of pups was observed in treated rats.
Food consumption: No data available
Gross pathology: No abnormal changes were observed in Gross pathology of pups.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 100 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from authoritative 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
Data available from different studies were reviewed to determine the reproductive toxicity of testchemical.The studies are as mentioned below:
Study 1
InCombined repeated dose reproduction /developmental toxicity study ,Crl: CD (SD) male and female rat treated withtest chemicalin the concentration of0, 20, 100, 500 mg/kg/dayorally.Toxic changes were observed as death in females at 500mg/kg/day,Salivation in male and female, decrease in locomotor activity, irregular respiration, prone position and drastic worsening in female, decrease in body weight gain andincrease food consumption in male rats. Significant decreases in red blood cell count, hemoglobin concentration, and hematocrit value of male and female rat, increase in A/G ratio, Pi, K and decreased BUN, TP and Cl level were observed in male rat and increase in ALT level in female rats when treated with 500 mg/kg/day. Changes in absolute and relative weigh of Brain, Liver, Kidney, Testes, Epididymides, Thymus and Spleen were observed. Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium in the testes, Decrease in sperm and Cell debris in the epididymides duct and increase in trabecular bone in the femur bone were observed in 500 mg/kg/day treated and in recovery period male and female rats.In addition,Decrease in gestation index,delivery index, number of corpora lutea, number of implantations, implantation index, number of offspring delivered and number of live offspring on days 0 and 4 were observed in 500 mg/kg/day.Therefore, NOAEL was considered to be100 mg/kg/dayforF0 and F1 generation when Crl:CD(SD) male and female rat treated withtest chemical orally for 42 days.
Study 2
In a Combined repeated dose reproduction /developmental toxicity study, VAF Crl: Swiss CD-l (ICR) BR outbred albino male and female mice treated with test chemical in the concentration of0, 0.35, 0.75 or 1.50% (Males: 0, 520, 1220 or 2780 mg/Kg/day; Females: 0, 540, 1340 or 3050 mg/Kg/day) orally in diet. Significant decrease were observed in body weight of male and female mice, Significant decrease in kidney weights (both absolute and adjusted), absolute ovary weight and absolute liver weight in female mice and absolute seminal vesicles weights in male mice when treated with 0.75 and 1.50 %. Significant decrease in mean number of litters per fertile pair, mean number of live pups per litter (both sexes) and live pup weight (absolute and adjusted) and Significant increase in cumulative days to litter for pairs were observed in 0.75 and 1.50 % treated mice. Mild Cystic Left Ovary and Amyloidosis were observed in 1.50 % treated female mice as compared to control in f0 generation. On F1 pups evaluation, Decreased in postnatal male and female pups survival, Significant decreased in postnatal body weight, absolute ovary, liver, absolute and adjusted kidney, seminal vesicle, right cauda and epididymis weights of treated male pups and absolute ovary, liver, kidney, seminal vesicle, right cauda and epididymis weights were significantly decrease and adjusted liver weight was significantly increased in female pups when treated with 1.50 %. Significant decreased in absolute liver weight of male pups at 0.75 % were observed. In addition, decreased in number of live female pups per litter and Minimal to Mild Cystic Ovary were observed in 0.75 and 1.50 % treated pups as compared to control. Therefore, The no-observed-adverse-effect-level (NOAEL) was considered to be 0.35 % (520 mg/kg/day for males and 540 mg/kg/day for females) for F0 and F1 generation when VAF Crl:Swiss CD-l (ICR)BR outbred albino male and female mice treated with test chemical.
Thus based on the above annotation and CLP criteria the test chemical is not likely to exhibit reproductive toxicant substance. Hence the substance cannot be classified as reproductive toxicant.
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 be100 mg /kg bw/day .When rats were treated with test chemical orally. Thus, comparing this value with the criteria ofCLP regulationtest chemicalis 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:
- 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 J check
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Test Guideline 422
- Principles of method if other than guideline:
- The 42 days feeding study was conducted on groups of 12 Males and 12 females Crl:CD(SD) rats to determine the developmental toxicity effect of test chemical
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data available
- Age at study initiation: 9 weeks old (initiation of dosing)
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available - Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- other: 0.1w/v% Tween 80 + 0.5w/v% Sodium carboxymethylcellulose solution
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:test chemical was disssolved in 0.1 w/v% Tween 80 + 0.5 w/v% Sodium carboxymethylcellulose solution at dose levels of 0, 20, 100 or 500 mg/Kg bw/day
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): 0.1 w/v% Tween 80 + 0.5 w/v% Sodium carboxymethylcellulose solution
- Concentration in vehicle: 0, 20, 100 or 500 mg/kg bw/day
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Details on mating procedure:
- No data available
- Duration of treatment / exposure:
- Males, 42 days
Females, from 14 days before mating to day 4 of lactation
Females (satellite), 42 days - Frequency of treatment:
- daily
- Duration of test:
- Males, 42 days
Females, from 14 days before mating to day 4 of lactation
Females (satellite), 42 days - Remarks:
- Doses / Concentrations:
0, 20, 100 or 500 mg/kg bw/day
Basis:
no data - No. of animals per sex per dose:
- Total: 116
0 mg/kg bw/day: 12 males, 12 females
20 mg/kg bw/day: 12 males, 12 females
100 mg/kg bw/day: 12 males, 12 females
500 mg/kg bw/day: 12 males, 12 females
For recovery
0 mg/kg bw/day: 5 males, 5 females
500 mg/kg bw/day: 5 males, 5 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: No data available
- Rationale for animal assignment (if not random): No data available
- Other: No data available - Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
- Cage side observations checked in table [No.?] were included. The animals were observed for mortality
DETAILED CLINICAL OBSERVATIONS: Yes, the animals were observed for salivation
- Time schedule: No data
BODY WEIGHT: Yes
- Time schedule for examinations: No data
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # No data
- Organs examined: Liver, sleen, thymus and kidney weight was examined
OTHER: Histopathology of forestomach, small and soft testes, small epididymides, seminiferous tubular epithelium in the testes, sperm in the epididymides duct, Cell debris in the epididymides duct, trabecular bone in the femur bone - Ovaries and uterine content:
- Implantation sites and corpora lutea were observed
- Fetal examinations:
- Number of pups delivered and number of live pups were examined.
- Statistics:
- No data available
- Indices:
- Gestation index, delivery index and implantation index were examined.
- Historical control data:
- No data available
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- 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:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- effects observed, treatment-related
- 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.
Remark: Decrease in the gestation index, delivery index, number of corpora lutea, number of implantation sites and implantation index (tendency) was noted at 500 mg/Kg/day
Mortality:
When treated with 500 mg/kg bw/day, three female rats died as compared to control.
Clinical signs:
Salivation was observed in 500 mg/kg bw/day treated male and female rats as compared to control.
Body weight and weight gain:
Restrained body weight gain was observed in 500 mg/kg bw/day treated male rat as compared to control.
Food consumption:
On day 8, Decrease in the food consumption was observed in 500 mg/kg bw/day treated male and female rat as compared to control.
Urinalysis:
No effects was observed in treated male and female rat as compared to control.
Hematology:
Decrease in the RBC, Hgb and Hct level were observed in 500 mg/kg bw/day treated male and female rat as compared to control.
Blood chemistry:
In male rats, Increase in the A/G ratio, Pi, K, and Decrease in Blood Urea Nitrogen, total protein and Cl level were observed in 500 mg/kg bw/day.
In female rats, Increase in ALT was observed in 500 mg/kg bw/day.
Organ weight:
In male rats, Increase in Relative brain, liver and kidney weight and Decrease in Absolute and Relative testes and epididymides weight during test and recovery and Absolute thymus weight during test were observed in 500 mg/kg bw/day.
In female, Increase in Relative liver and spleen weight during test and recovery and Absolute spleen and kidney weight in recovery and Decrease in Absolute thymus weight during test were observed in 500 mg/kg bw/day.
Reproductive performs:
Decrease in gestation index, delivery index, number of corpora lutea, number of implantation sites, implantation index and number of pups delivered were observed in 500 mg/kg bw/day treated female rats.
Histopathology:
In male rat, Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium of testes, Decrease sperm in the epididymides duct, Cell debris in epididymides duct and Increase in the trabecular bone in femur bone were observed in 500 mg/kg bw/day during treatment and recovery.
In female rat, Squamous hyperplasia and Erosion in forestomach during test and Increase in trabecular bone in femur bone during test and Recovery at in 500 mg/kg bw/day treated female rats. - Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: Significant alterations were noted at 500 mg/Kg/day
- Remarks on result:
- other: Not toxic at the mentioned dose level
- Abnormalities:
- not specified
- Fetal body weight changes:
- not specified
- Reduction in number of live offspring:
- effects observed, treatment-related
- 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:
- not specified
- Visceral malformations:
- not specified
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes. Remark: Decrease in number of pups delivered, number of live pups on day 0 and number of live pups on day 4 in 500 mg/kg bw/day treated female rats was noted
- Dose descriptor:
- NOAEL
- Effect level:
- 100 other: mg/Kg/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Significant treatment related effects were noted at 500 mg/Kg/day
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) was considered to be 100 mg/kg body/day for F0 and F1 generation when Crl:CD (SD) male and female rats were treated with test chemical
- Executive summary:
In Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test, Crl:CD (SD) male and female rats were treated with test chemical in the concentration of 0, 20, 100 and 500 mg/kg bw/day orally by gavage. In F0 generation, when treated with 500 mg/kg/day, three female rats died, Salivation in male and female rat was noted, restrained body weight gain in male rat and decrease in the food consumption on day 8 in male and female rat were observed. Similarly, Decrease in the RBC, Hgb and Hct level in male and female rat, Increase in A/G ratio, Pi, K and Decrease in Blood Urea Nitrogen, total protein, Cl level in male rat and Increase in ALT level in female rat were observed in 500 mg/kg/day. In addition, Increase in Relative brain, liver and kidney weight and Decrease in absolute and relative testes and epididymides weight during test and recovery and absolute thymus weight during test in male rat and Increase in relative liver and spleen weight during test and recovery and absolute spleen and kidney weight in recovery and Decrease in absolute thymus weight during test in female, Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium of testes, decrease sperm and cell debris in epididymides duct and an increase in the trabecular bone in femur bone in male rat and squamous hyperplasia and erosion in forestomach during test and an increase in trabecular bone in femur bone during test and recovery in female rat treated with 500 mg/kg/day. Decrease in gestation index, delivery index, number of corpora lutea, number of implantation sites, implantation index and number of pups delivered in F0 female and a decrease in number of pups delivered, number of live pups on day 0 and number of live pups on day 4 were observed in F1 generation treated with 500 mg/kg bw/day female rats. Based on the observations made, No Observed Adverse Effect Level (NOAEL) was considered to be 100 mg/kg body/day for F0 and F1 generation when Crl:CD (SD) male and female rats were treated with test
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 100 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data available from J check
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
InCombined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test,Crl:CD (SD) male and female rats treated with test chemical in the concentration of 0, 20, 100 and 500 mg/kg bw/day orally by gavage. In F0 generation, when treated with 500 mg/kg/day,Three female rats died, Salivation in male and female rat,Restrained body weight gain in male rat andDecrease in the food consumption on day 8 in male and female rat were observed. Similarly, Decrease in the RBC, Hgb and Hct level in male and female rat, Increase in A/G ratio, Pi, K and Decrease in Blood Urea Nitrogen, total protein, Cl level in male rat and Increase in ALT level in female rat were observed in 500 mg/kg/day. In addition, Increase in Relative brain, liver and kidney weight and Decrease in absolute and relative testes and epididymides weight during test and recovery and absolute thymus weight during test in male rat and Increase in relative liver and spleen weight during test and recovery and absolute spleen and kidney weight in recovery and Decrease in absolute thymus weight during test in female, Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium of testes, Decrease sperm and Cell debris in epididymides duct and Increase in the trabecular bone in femur bone in male rat and Squamous hyperplasia and Erosion in forestomach during test and Increase in trabecular bone in femur bone during test and recovery in female rat treated with 500 mg/kg/day. Decrease in gestation index, delivery index, number of corpora lutea, number of implantation sites, implantation index and number of pups delivered in F0 female andDecrease in number of pups delivered, number of live pups on day 0 and number of live pups on day 4 were observed in F1 generation treated with500 mg/kg bw/day female rats. Therefore,NOAEL was considered to be 100mg/kg body weight/dayfor F0 and F1 generation when Crl: CD (SD) male and female rats were treated with test chemical orally by gavage for 42 days.
Study 2
In a Inhalation developmental toxicity, Wistar female rat were treated with test chemicalin the concentration of 0, 0.4, 1.0 and 2.9 mg/m3by whole body inhalation.Significant increase in aspartate aminotransferase, alanine aminotransferase and lipid peroxidation.Dose dependent retardation of the body weight andSignificantly decrease in relative liver weights of 1.0 and 2.9 mg/m3treated female rat were observed.Significantly increased in embryolethalitywas observed in1.0 and 2.9 mg/m3treated female rat.On F1 generation evaluation, Significant changes in behavior in the open field test,significantly decreased in relative weight of liver, heart; lungs and adrenal gland were observed in pups at 0 and 2.9 mg/m3. In addition, Significantly decrease in number of metacarpal bones and number of ribs and Significant delayed in Upper and lower incisor eruption was observed in 2.9 mg/m3treated pups. Therefore, NOEL was considered to be 0.4 mg/m3for Wistar female rat when treated with test chemical by whole body inhalation.
Thus, based on the data available fortest chemical,Low Observed Adverse Effect Level (NOAEL) was considered to be 100 mg /kg bw .When rats were treated with test chemical orally. Thus, comparing this value with the criteria of CLP regulationtest chemicalis not likely to classify as reproductive and developmental toxicant.
Justification for classification or non-classification
Test chemical is found to exhibit non toxic reproductive effects. Also, the majority use of this chemical is used as a solvent form to color topical drug preparations and cosmetics. Thus, exposure to high levels of test chemical is likely to be minimal and hence the chemical has not be considered as toxic to reproduction and developmental toxicity for classification
Additional information
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