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EC number: 203-973-1 | CAS number: 112-45-8
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- 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:
- Weight of evidence approach based on the available information from various test chemicals.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Qualifier:
- according to guideline
- Guideline:
- other: Combined repeated and reproductive developmental toxicity screening test
- Principles of method if other than guideline:
- The above experiment was performed to assess and evaluate the toxicity of the test chemical on the reproductive and developmental toxicity parameters of the Sprague Dawley Rats.
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Molecular formula (if other than submission substance): C7H14O2
- Molecular weight (if other than submission substance): 130.29 g/mol
- Substance type: Organic
- Physical state: Liquid - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: No data available
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): No data available
- Concentration in vehicle: 0, 200, 1000 or 2000 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 Available
- Details on mating procedure:
- - M/F ratio per cage: No Data Available
- Length of cohabitation: No data available
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available
- Further matings after two unsuccessful attempts: No data available
- Verification of same strain and source of both sexes: No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy No data available
- Any other deviations from standard protocol: No data available - Duration of treatment / exposure:
- For one week prior to a 7-day cohabitation period through gestation, parturition and a 4-day postpartum period.
- Frequency of treatment:
- No Data Available
- Duration of test:
- No Data Available
- Remarks:
- Doses / Concentrations:
0, 200, 1000 and 2000 mg/kg-bw/day - No. of animals per sex per dose:
- No Data Available
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No Data Available
- Maternal examinations:
- Maternal animals were observed for Mortality, clinical signs, food consumption, body weights, mating and fertility,
- Ovaries and uterine content:
- Number of implantation and losses were investigated.
- Fetal examinations:
- Fetal examinations included implantations, length of gestation, proportion of dams delivering live pup or pup viability, Pup weights, malformations and gross lesions.
- Statistics:
- No Data Available
- Indices:
- No Data Available
- Historical control data:
- No Data Available
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 1000 and 2000 mg/kg-bw/day dose groups, significant increases in the incidence of rales (p < 0.01) and excess salivation (p < 0.01) were reported during pre-mating and gestation. High-dose females also exhibited lethargy, unkempt coats and labored breathing.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Mortality occurred in the high-dose group (3 of 10 rats) and mid-dose group (1 of 10 rats)
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Average maternal body weights were decreased on days 10 – 16 of gestation and body weight gains were significantly (p < 0.05) reduced.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- In the high-dose group, food consumption was reduced throughout the study.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed - Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- changes in pregnancy duration
- dead fetuses
- early or late resorptions
- effects on pregnancy duration
- food consumption and compound intake
- mortality
- number of abortions
- pre and post implantation loss
- total litter losses by resorption
- Abnormalities:
- not specified
- Fetal body weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Pup weights were reduced on day 4 post parturition in the high-dose group.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): effects observed, non-treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): Pup weights were reduced on day 4 post parturition in the high-dose group. - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Skeletal malformations:
- not specified
- Visceral malformations:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 2 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
- fetal/pup body weight changes
- changes in litter size and weights
- external malformations
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Based on all the observation it was concluded that, NOAEL was considered to be 200 and 2000 mg/kg body weight/day for the maternal generation and the F1 generation respectively.
- Executive summary:
- In a reproductive/developmental toxicity study, female Sprague-Dawley rats (10/group) were administered with the test chemical via gavage (in corn oil) at doses of 0, 200, 1000 or 2000 mg/kg-bw/day for one week prior to a 7-day cohabitation period through gestation, parturition and a 4-day postpartum period. The parental animals were observed for Mortality, clinical signs, food consumption, body weights, mating and fertility, while Fetal examinations included implantations, length of gestation, proportion of dams delivering live pup or pup viability, Pup weights, malformations and gross lesions. After all the examinations it was observed that in maternal animals, mortality occured in high dose group. In clinical signs, in the 1000 and 2000 mg/kg-bw/day dose groups, significant increases in the incidence of rales (p < 0.01) and excess salivation (p < 0.01) were reported during pre-mating and gestation. High-dose females also exhibited lethargy, unkempt coats and labored breathing. Also, average maternal body weights were decreased on days 10 – 16 of gestation and body weight gains were significantly (p < 0.05) reduced. In the high-dose group, food consumption was reduced throughout the study. Although, no effects were observed in pre and post implantation loss, resorptions, viability of the pups and pregnancy duration in maternal animals. In pup parameters, no effects were observed in change in number of offsprings and litter size, and no external anomalies were observed at any dose levels. Thus, based on all the observation it was concluded that, NOAEL was considered to be 200 and 2000 mg/kg body weight/day for the maternal generation and the F1 generation respectively.
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data is from a secondary source.
- Qualifier:
- according to guideline
- Guideline:
- other: Combined Repeated and Reproductive Developmental Toxicity Screening Test
- Principles of method if other than guideline:
- The above experiment was performed to evaluate and assess the reproductive toxicity of the test chemical in rats.
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Molecular formula (if other than submission substance): C14-H28
- Molecular weight (if other than submission substance): 196.375 g/mol
- Substance type: Organic
- Physical state: No Data Available
- Impurities (identity and concentrations): No Data Available - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on exposure:
- Male rats were exposed for 28 days prior to mating, and through mating until euthanasia for a total of 43-47 consecutive days of dosing; while 12 females were dosed for 14 days prior to mating, during mating, gestation and lactation through euthanasia at lactation day 4 (42-51 consecutive days).
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No Data Available
- Details on mating procedure:
- No Data Available
- Duration of treatment / exposure:
- Males: 43-47 consecutive days
Females: 42-51 consecutive days - Frequency of treatment:
- No Data Available
- Duration of test:
- No Data Available
- Remarks:
- Doses / Concentrations:
0, 100, 500 or 1000 mg/kg-bw/day
Basis:
no data - No. of animals per sex per dose:
- 24 animals were used per group.
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Further 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:
- The parental animals were observed for neurotoxic and pathological analyses.
- Ovaries and uterine content:
- No Data Available
- Fetal examinations:
- Pup viability, pup weights and malformations or gross lesions were observed.
- Statistics:
- No Data Available
- Indices:
- Copulation and fertility index, gestational index and pup viability indices
- Historical control data:
- No Data Available
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- It was observed that hepatocyte cytoplasmic vacuolation occurred in both sexes at >500 mg/kg/day (associated with an increase in liver weight), and pitted kidneys and accumulation of hyaline droplets in the proximal convoluted tubules of the kidneys of males at all dose levels. The kidney effects were interpreted to be a result of hydrocarbon nephropathy, which is specific to male rats.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The adverse effect observed was liver effect in non-pregnant satellite females histologically examined.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed - Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Details on maternal toxic effects:
- No Data Available
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- changes in pregnancy duration
- dead fetuses
- gross pathology
- histopathology: non-neoplastic
- number of abortions
- Abnormalities:
- not specified
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Skeletal malformations:
- not specified
- Visceral malformations:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
- changes in sex ratio
- fetal/pup body weight changes
- changes in litter size and weights
- external malformations
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Based on all the above observations it was concluded that the NOEL for parental animals was found to be 100 mg/kg bw/day and the NOAEL for F1 generation was found to be 1000 mg/kg bw/day.
- Executive summary:
A combined repeated and reproductive/developmental toxicity screening test was performed to assess and evaluate the reproductive toxicity of the test chemical in rats. In this test, the rats were dosed with the test chemical using three dose groups of 100, 500 and 1000 mg/kg bw/day. A concurrent control group and a satellite group was also used. A total of 14 animals were used per group in this study. Male rats were exposed for 28 days prior to mating, and through mating until euthanasia for a total of 43-47 consecutive days of dosing; while 12 females were dosed for 14 days prior to mating, during mating, gestation and lactation through euthanasia at lactation day 4 (42-51 consecutive days). The parental animals were observed for pathological changes and neurotoxicity. After the examinations, it was observed that, hepatocyte cytoplasmic vacuolation occurred in both sexes at >500 mg/kg/day (associated with an increase in liver weight), and pitted kidneys and accumulation of hyaline droplets in the proximal convoluted tubules of the kidneys of males at all dose levels. The kidney effects were interpreted to be a result of hydrocarbon nephropathy, which is specific to male rats. Also, the determined NOEL was 100 mg/kg/day which was determined by the effect of liver through histopathological examination in non-pregnant satellite females. In reproductive parameters of the rats, there was no effects observed on copulation and fertility, precoital intervals, gestation length, time to delivery or unusual nesting behavior. In pup parameters, mortality/viability of the pups, litter size and body weights, male to female pup ratio and external anomalies. After all examinations, no effects were observed in any of the pup parameters. Thus, based on all the above observations it was concluded that the NOEL for parental animals was found to be 100 mg/kg bw/day and the NOAEL for F1 generation was found to be 1000 mg/kg bw/day.
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data is from a secondary literature source.
- Qualifier:
- according to guideline
- Guideline:
- other: Reproduction and Developmental Toxicity Screening Test
- Principles of method if other than guideline:
- The above experiment was performed to evaluate and assess the reproductive and developmental toxicity potential of the test chemical in male and female rats.
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- Details on test material:
-Molecular Formula: C6-H12
- Molecular weight (if other than submission substance): 84.1608 g/mol
- Substance type: Organic
- Physical state: No Data Available
- Impurities (identity and concentrations): No Data Available - Species:
- rat
- Strain:
- not specified
- Details on test animals or test system and environmental conditions:
- No Data Available
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- Details on exposure
PREPARATION OF DOSING SOLUTIONS: No Data Available
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): The test chemical was best miscible in corn oil.
- Concentration in vehicle: 0, 100, 500 and 1000 mg/kg
- 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 Available
- Details on mating procedure:
- No Data Available
- Duration of treatment / exposure:
- Male rats were treated for 28 days prior to mating and for an additional 16 days (44 total days).
Females were dosed for 14 days prior to mating and during mating, gestation and lactation (41-55 days). - Frequency of treatment:
- No Data Available
- Duration of test:
- No Data Available
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Control Group
- Dose / conc.:
- 100 mg/kg bw/day
- Remarks:
- Low Dose Group
- Dose / conc.:
- 500 mg/kg bw/day
- Remarks:
- Mid Dose Group
- Dose / conc.:
- 1 000 mg/kg bw/day
- Remarks:
- High Dose Group
- No. of animals per sex per dose:
- No Data Available
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No Data Available
- Maternal examinations:
- Maternal animals were examined for precoital intervals, gestation length, pregnancy rats, copulation, fertility indices
- Ovaries and uterine content:
- No Data Available
- Fetal examinations:
- Number of litters, pup survival, pup viability, pup weight, and sex ratio.
- Statistics:
- No Data Available
- Indices:
- No Data Available
- Historical control data:
- No Data Available
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- No Data Availablr
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed - Changes in number of pregnant:
- no effects observed
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- changes in number of pregnant
- changes in pregnancy duration
- dead fetuses
- early or late resorptions
- effects on pregnancy duration
- number of abortions
- pre and post implantation loss
- total litter losses by resorption
- Abnormalities:
- not specified
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- not specified
- Skeletal malformations:
- not specified
- Visceral malformations:
- not specified
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- No Data Available
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
- changes in sex ratio
- fetal/pup body weight changes
- changes in litter size and weights
- changes in postnatal survival
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- Based on all the above observations, it was concluded that, the NOAEL for both maternal and fetal parameters based on the test chemical was found to be 1000 mg/kg bw/day.
- Executive summary:
An experiment was conducted to assess the reproductive and developmental toxicity potential of the test chemical in rats. In this experiment, the test chemical was mixed with the corn oil and administered orally to the animals in the dose groups of 0, 100, 500 and 1000 mg/kg bw/day. Male rats were treated for 28 days prior to mating and for an additional 16 days (44 total days). Females were dosed for 14 days prior to mating and during mating, gestation and lactation (41-55 days). During and after the dosing the animals were observed for any adverse effects of the test chemicals. After dosing, it was observed that there were no adverse effects observed in maternal animals at any given dose levels. However, in male rats, absolute epididymal weights for males were statistically lower in all treated groups compared to controls and the epididymal/brain relative weights were also lower in all treated groups compared to controls, although only the low dose group was statistically significant. The biological significance of the decreased epididymal weights was found to be uncertain because of no apparent histopathological effects in the epididymis and no evidence of impared fertility in the treated males and there was a lack of a dose response between treated groups. In maternal parameters, there were no effects on the following reproductive parameters: precoital intervals, gestation length, pregnancy rats, copulation and fertility indices. Also, in developmental parameters, it was observed that, there were no effects on the number of litters, pup survival, pup viability, pup weight, and sex ratio. Thus, based on all the above observations, it was concluded that, the NOAEL for both maternal and fetal parameters based on the test chemical was found to be 1000 mg/kg bw/day.
Data source
Reference
- Reference Type:
- publication
- Title:
- WoE for developmental toxicity study for CAS no 112-45-8
- Author:
- Sustainability Support Services (Europe) AB
- Year:
- 2 018
- Bibliographic source:
- WoE report, Sustainability Support Services (Europe) AB, 2018
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: Study 2: Combined Repeated and Reproductive Developmental Toxicity Screening Test
- Qualifier:
- according to guideline
- Guideline:
- other: Study 3: Combined Repeated and Reproductive Developmental Toxicity Screening Test
- Qualifier:
- according to guideline
- Guideline:
- other: Study 4: Reproductive and Developmental Toxicity Screening Test
- Principles of method if other than guideline:
- WoE report is based on three developmental toxicity studies on rats:
Study 2 and 3: Combined Repeated and Reproductive Developmental Toxicity Screening Test
Study 4: Reproductive and Development Toxicity Screning Test
All the above experiments were performed to assess and evaluate the reproducive and developmental toxicity of the test chemical in the test animals (rats). - GLP compliance:
- not specified
Test material
- Reference substance name:
- Undec-10-enal
- EC Number:
- 203-973-1
- EC Name:
- Undec-10-enal
- Cas Number:
- 112-45-8
- Molecular formula:
- C11H20O
- IUPAC Name:
- undec-10-enal
- Details on test material:
- - Molecular formula (if other than submission substance): C11-H20-O
- Molecular weight (if other than submission substance): 168.278 g/mole
- Substance type: Organic
Constituent 1
- Specific details on test material used for the study:
- - Molecular formula (if other than submission substance): C11-H20-O
- Molecular weight (if other than submission substance): 168.278 g/mole
- Substance type: Organic
Test animals
- Species:
- rat
- Strain:
- other: Study 2 and 3: Sprague Dawley; Study 3: Not Specified
- Details on test animals or test system and environmental conditions:
- Study 2, Study 3 and 4: No Data Available
Administration / exposure
- Route of administration:
- other: Study 2, 3 and 4: Oral
- Vehicle:
- other: Study 2 and 4: Corn Oil and Study 3: Not Specified
- Details on exposure:
- Study 2: PREPARATION OF DOSING SOLUTIONS: No data available
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): No data available
- Concentration in vehicle: 0, 200, 1000 or 2000 mg/kg-bw/day
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Study 3: Male rats were exposed for 28 days prior to mating, and through mating until euthanasia for a total of 43-47 consecutive days of dosing; while 12 females were dosed for 14 days prior to mating, during mating, gestation and lactation through euthanasia at lactation day 4 (42-51 consecutive days).
Study 4: Details on exposure
PREPARATION OF DOSING SOLUTIONS: No Data Available
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): The test chemical was best miscible in corn oil.
- Concentration in vehicle: 0, 100, 500 and 1000 mg/kg
- 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:
- Study 2, 3 and 4: No Data Available
- Details on mating procedure:
- Study 2: - M/F ratio per cage: No Data Available
- Length of cohabitation: No data available
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available
- Further matings after two unsuccessful attempts: No data available
- Verification of same strain and source of both sexes: No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy No data available
- Any other deviations from standard protocol: No data available
Study 3 and 4: No Data Available - Duration of treatment / exposure:
- Study 2: For one week prior to a 7-day cohabitation period through gestation, parturition and a 4-day postpartum period.
Study 3: Males: 43-47 consecutive days
Females: 42-51 consecutive days
Study 4: Male rats were treated for 28 days prior to mating and for an additional 16 days (44 total days).
Females were dosed for 14 days prior to mating and during mating, gestation and lactation (41-55 days). - Frequency of treatment:
- Study 2, 3 and 4: No Data Available
- Duration of test:
- Study 2, 3 and 4: No Data Available
Doses / concentrations
- Remarks:
- Study 2: 0, 200, 1000 and 2000 mg/kg bw/day
Study 3 and 4: 0, 100, 500 or 1000 mg/kg bw/day
- No. of animals per sex per dose:
- Study 2 and 4: No Data Available
Study 3: 24 animals were used per group. - Control animals:
- other: Study 2,3 and 4: Yes, Concurrent Vehicle
- Details on study design:
- Study 2 and 4: No Data Available
Study 3: Further details on study design:
- Dose selection rationale: No Data Available
- Rationale for animal assignment (if not random): No Data Available
- Other: No Data Available
Examinations
- Maternal examinations:
- Study 2: Maternal animals were observed for Mortality, clinical signs, food consumption, body weights, mating and fertility,
Study 3: The parental animals were observed for neurotoxic and pathological analyses.
Study 4: Maternal animals were examined for precoital intervals, gestation length, pregnancy rats, copulation, fertility indices - Ovaries and uterine content:
- Study 2: Number of implantation and losses were investigated.
Study 3 and 4: No Data Available - Fetal examinations:
- Study 2: Fetal examinations included implantations, length of gestation, proportion of dams delivering live pup or pup viability, Pup weights, malformations and gross lesions.
Study 3: Pup viability, pup weights and malformations or gross lesions were observed.
Study 4: Number of litters, pup survival, pup viability, pup weight, and sex ratio. - Statistics:
- Study 2, 3 and 4: No Data Available
- Indices:
- Study 3: Copulation and fertility index, gestational index and pup viability indices
Study 2 and 4: No Data Available - Historical control data:
- No Data Available
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 2: In the 1000 and 2000 mg/kg-bw/day dose groups, significant increases in the incidence of rales (p < 0.01) and excess salivation (p < 0.01) were reported during pre-mating and gestation. High-dose females also exhibited lethargy, unkempt coats and labored breathing.
Study 3 and 4: No Data Available - Dermal irritation (if dermal study):
- not specified
- Description (incidence and severity):
- Study 2, 3 and 4: No Data Available
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Study 2: Mortality occurred in the high-dose group (3 of 10 rats) and mid-dose group (1 of 10 rats).
Study 3 and 4: No Data Available - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 2: Average maternal body weights were decreased on days 10 – 16 of gestation and body weight gains were significantly (p < 0.05) reduced.
Study 3 and 4: No Data Available - Food consumption and compound intake (if feeding study):
- not specified
- Description (incidence and severity):
- Study 2: In the high-dose group, food consumption was reduced throughout the study.
Study 3 and 4: No Data Available - Food efficiency:
- not specified
- Description (incidence and severity):
- Study 2, 3 and 4: No Data Available
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- Study 4: No effects were observed in any of the dose levels.
Study 2 and 3: No Data Available - Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 3: It was observed that hepatocyte cytoplasmic vacuolation occurred in both sexes at >500 mg/kg/day (associated with an increase in liver weight), and pitted kidneys and accumulation of hyaline droplets in the proximal convoluted tubules of the kidneys of males at all dose levels. The kidney effects were interpreted to be a result of hydrocarbon nephropathy, which is specific to male rats.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 3: The adverse effect observed was liver effect in non-pregnant satellite females histologically examined.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- No Data Available
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- Study 2, 3 and 4: No effects were observed on abortion of fetus at any dose levels.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- Study 2 and 4: No effects were observed at any dose levels on pre-- and post-implantation losses.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- Study 2 and 4: No effects were observed on the litter losses at given dose levels.
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- Study 2 and 4: No early or late resorptions were observed at any dose levels.
- Dead fetuses:
- not specified
- Description (incidence and severity):
- Study 2, 3 and 4: No fetuses were found dead at any dose levels.
- Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- Study 2, 3 and 4: No changes were observed in pregnancy duration of the female rats.
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.DescriptionIncidenceAndSeverityEffectsOnPregnancyDuration): Study 2, 3 and 4: No effects were observed on the pregnancy duration at any given dose levels. - Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- Study 4: No changes were observed in the number of pregnant females at any dose levels.
- Other effects:
- not specified
- Details on maternal toxic effects:
- No Data Available
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- changes in number of pregnant
- changes in pregnancy duration
- dead fetuses
- early or late resorptions
- effects on pregnancy duration
- food consumption and compound intake
- mortality
- number of abortions
- pre and post implantation loss
- total litter losses by resorption
Maternal abnormalities
- Abnormalities:
- not specified
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Study 2: Pup weights were reduced on day 4 post parturition in the high-dose group.
Study 3 and 4: No effects were observed
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): effects observed, treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): Study 2: Pup weights were reduced on day 4 post parturition in the high-dose group.
Study 3 and 4: No effects were observed - Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- Study 2, 3 and 4: No effects were observed in reduction in number of live offsprings.
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- Study 3 and 4: No changes in sex ratio were observed at given dose levels.
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- Study 2, 3 and 4: No changes were observed in liiter size and their weights at any dose levels.
- Changes in postnatal survival:
- no effects observed
- Description (incidence and severity):
- Study 4: No changes were observed in post natal survival at any dose levels.
- External malformations:
- no effects observed
- Description (incidence and severity):
- Study 3: No external malformations were obsrved at any dose levels.
- Skeletal malformations:
- not specified
- Visceral malformations:
- not specified
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- No Data Available
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
- changes in sex ratio
- fetal/pup body weight changes
- changes in litter size and weights
- changes in postnatal survival
- external malformations
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Study 2: Based on all the observation it was concluded that, NOAEL was considered to be 200 and 2000 mg/kg body weight/day for the maternal generation and the F1 generation respectively.
Study 3: Based on all the above observations it was concluded that the NOEL for parental animals was found to be 100 mg/kg bw/day and the NOAEL for F1 generation was found to be 1000 mg/kg bw/day.
Study 4: Based on all the above observations, it was concluded that, the NOAEL for both maternal and fetal parameters based on the test chemical was found to be 1000 mg/kg bw/day. - Executive summary:
Developmental Toxicity Study Summaries:
Study 2:
In a reproductive/developmental toxicity study, female Sprague-Dawley rats (10/group) were administered with the test chemical via gavage (in corn oil) at doses of 0, 200, 1000 or 2000 mg/kg-bw/day for one week prior to a 7-day cohabitation period through gestation, parturition and a 4-day postpartum period. The parental animals were observed for Mortality, clinical signs, food consumption, body weights, mating and fertility, while Fetal examinations included implantations, length of gestation, proportion of dams delivering live pup or pup viability, Pup weights, malformations and gross lesions. After all the examinations it was observed that in maternal animals, mortality occured in high dose group. In clinical signs, in the 1000 and 2000 mg/kg-bw/day dose groups, significant increases in the incidence of rales (p < 0.01) and excess salivation (p < 0.01) were reported during pre-mating and gestation. High-dose females also exhibited lethargy, unkempt coats and labored breathing. Also, average maternal body weights were decreased on days 10 – 16 of gestation and body weight gains were significantly (p < 0.05) reduced. In the high-dose group, food consumption was reduced throughout the study. Although, no effects were observed in pre and post implantation loss, resorptions, viability of the pups and pregnancy duration in maternal animals. In pup parameters, no effects were observed in change in number of offsprings and litter size, and no external anomalies were observed at any dose levels. Thus, based on all the observation it was concluded that, NOAEL was considered to be 200 and 2000 mg/kg body weight/day for the maternal generation and the F1 generation respectively.
Study 3:
A combined repeated and reproductive/developmental toxicity screening test was performed to assess and evaluate the reproductive toxicity of the test chemical in rats. In this test, the rats were dosed with the test chemical using three dose groups of 100, 500 and 1000 mg/kg bw/day. A concurrent control group and a satellite group was also used. A total of 14 animals were used per group in this study. Male rats were exposed for 28 days prior to mating, and through mating until euthanasia for a total of 43-47 consecutive days of dosing; while 12 females were dosed for 14 days prior to mating, during mating, gestation and lactation through euthanasia at lactation day 4 (42-51 consecutive days). The parental animals were observed for pathological changes and neurotoxicity. After the examinations, it was observed that, hepatocyte cytoplasmic vacuolation occurred in both sexes at >500 mg/kg/day (associated with an increase in liver weight), and pitted kidneys and accumulation of hyaline droplets in the proximal convoluted tubules of the kidneys of males at all dose levels. The kidney effects were interpreted to be a result of hydrocarbon nephropathy, which is specific to male rats. Also, the determined NOEL was 100 mg/kg/day which was determined by the effect of liver through histopathological examination in non-pregnant satellite females. In reproductive parameters of the rats, there was no effects observed on copulation and fertility, precoital intervals, gestation length, time to delivery or unusual nesting behavior. In pup parameters, mortality/viability of the pups, litter size and body weights, male to female pup ratio and external anomalies. After all examinations, no effects were observed in any of the pup parameters. Thus, based on all the above observations it was concluded that the NOEL for parental animals was found to be 100 mg/kg bw/day and the NOAEL for F1 generation was found to be 1000 mg/kg bw/day.
A combined repeated and reproductive/developmental toxicity screening test was performed to assess and evaluate the reproductive toxicity of the test chemical in rats. In this test, the rats were dosed with the test chemical using three dose groups of 100, 500 and 1000 mg/kg bw/day. A concurrent control group and a satellite group was also used. A total of 14 animals were used per group in this study. Male rats were exposed for 28 days prior to mating, and through mating until euthanasia for a total of 43-47 consecutive days of dosing; while 12 females were dosed for 14 days prior to mating, during mating, gestation and lactation through euthanasia at lactation day 4 (42-51 consecutive days). The parental animals were observed for pathological changes and neurotoxicity. After the examinations, it was observed that, hepatocyte cytoplasmic vacuolation occurred in both sexes at >500 mg/kg/day (associated with an increase in liver weight), and pitted kidneys and accumulation of hyaline droplets in the proximal convoluted tubules of the kidneys of males at all dose levels. The kidney effects were interpreted to be a result of hydrocarbon nephropathy, which is specific to male rats. Also, the determined NOEL was 100 mg/kg/day which was determined by the effect of liver through histopathological examination in non-pregnant satellite females. In reproductive parameters of the rats, there was no effects observed on copulation and fertility, precoital intervals, gestation length, time to delivery or unusual nesting behavior. In pup parameters, mortality/viability of the pups, litter size and body weights, male to female pup ratio and external anomalies. After all examinations, no effects were observed in any of the pup parameters. Thus, based on all the above observations it was concluded that the NOEL for parental animals was found to be 100 mg/kg bw/day and the NOAEL for F1 generation was found to be 1000 mg/kg bw/day.
Study 4:
An experiment was conducted to assess the reproductive and developmental toxicity potential of the test chemical in rats. In this experiment, the test chemical was mixed with the corn oil and administered orally to the animals in the dose groups of 0, 100, 500 and 1000 mg/kg bw/day. Male rats were treated for 28 days prior to mating and for an additional 16 days (44 total days). Females were dosed for 14 days prior to mating and during mating, gestation and lactation (41-55 days). During and after the dosing the animals were observed for any adverse effects of the test chemicals. After dosing, it was observed that there were no adverse effects observed in maternal animals at any given dose levels. However, in male rats, absolute epididymal weights for males were statistically lower in all treated groups compared to controls and the epididymal/brain relative weights were also lower in all treated groups compared to controls, although only the low dose group was statistically significant. The biological significance of the decreased epididymal weights was found to be uncertain because of no apparent histopathological effects in the epididymis and no evidence of impared fertility in the treated males and there was a lack of a dose response between treated groups. In maternal parameters, there were no effects on the following reproductive parameters: precoital intervals, gestation length, pregnancy rats, copulation and fertility indices. Also, in developmental parameters, it was observed that, there were no effects on the number of litters, pup survival, pup viability, pup weight, and sex ratio. Thus, based on all the above observations, it was concluded that, the NOAEL for both maternal and fetal parameters based on the test chemical was found to be 1000 mg/kg bw/day.
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