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EC number: 457-330-7 | CAS number: 66034-17-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
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- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
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- Additional physico-chemical information
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- Endpoint summary
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- Environmental data
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- 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
Effects on fertility
Description of key information
The Reproduction/Developmental Toxicity Screening Test (OECD 421) included a developmental toxicity-screening test, intended to provide information on possible effects on the development of the F1 offspring from conception to Day 4 post-partum.
Male and female Wistar rats were treated for 2 weeks pre-mating, then during the mating/postmating period, males for 28 days and females throughout gestation period, up to and including postpartum/lactation Day PPD4. The offspring were not dosed.
The ovaries and uterine content was examined after termination of the dams on Day 5-7 post-partum. Numbers of corpora lutea, implantations and the post implantation survival were determined, gestation length was recorded.
Offspring examinations: clinical signs, body weight, body weight gain, number of live births and of viable pups per litter on postnatal Days 0 and 4, sex ratio.
There were no adverse effects on the maternal animals.
There were no adverse effects on the F1 offspring viability, clinical signs or development.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: The United States EPA Health Effects Test Guidelines, OPPTS 870.3550, Reproduction/Developmental Toxicity Screening Test, July 2000.
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Wistar rats, strain: Crl:WI(Han)
- Source: Charles River Deutschland, Sulzfeld
- Age at treatment start: approx. 12 weeks old, both sexes
- Housing in Macrolon plastic cages
during pre-pairing dosing period: In groups of 5 by sex
during pairing: 1 male+1 female/cage
males after pairing: In groups of 5
females during gestation and lactation: Females housed individually (+litter).
- Bedding material (in Macrolon plastic cages): sterilised sawdust as bedding, paper as enrichment and nesting material
- Diet (ad libitum): pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water (ad libitum): tap water
- Acclimation period: 5 days before treatment start
ENVIRONMENTAL CONDITIONS
The animal room was maintained at (target ranges for temperature and relative humidity):
- Temperature (°C): 18 - 24°C
- Relative Humidity (%): 40 - 70 %
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night
- Ventilation: at least 10 room air changes/h - Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 1% aqueous
- Details on exposure:
- - Amount (dose volume by gavage): 5 mL/kg bw/day.
Actual dose volumes were calculated accounting for the latest bodyweight.
- Frequency of preparation of dose formulations: daily within 6 hours prior to dosing
Treatment of parental animals by oral gavage administration. Test substance was not directly administered to F1 animals. - Details on mating procedure:
- - Male/female ratio per cage: 1/1
- Length of cohabitation: At the most 14 days, until proof of pregnancy was confirmed.
- Proof of pregnancy: Formation of vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- For analysis of the test substance in the vehicle LC/MS was used with a Hypersil BDS C18 column (100 mm x 4.6 mm i.d., dp = 5 µm). The analytical method was validated. The mean contents of the test substance in dose formulations were found to be well within the acceptance limit (within +/- 15%) of dose theoretical concentration; the relative standard deviation was equal to or less than 10%.
- Duration of treatment / exposure:
- - Treatment period, parental males: 28 days (14 days before mating, during mating and up to the day prior to scheduled necropsy)
- Treatment period, parental females (dams): 41-54 days (from 14 days prior to mating to at least Lactation Day 4)
- Pups were not treated directly (possibly via milk): until Lactation Day 4. - Frequency of treatment:
- Daily
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Positive control:
- Not included in the study.
- Parental animals: Observations and examinations:
- Clinical observations performed and frequency:
- Clinical signs: Daily (covering external appearance, motor activity & morbidity in each animal)
- Body weight, Males: Weekly from Treatment Day 0 to 28.
Body weight, Females: Weekly for pre-pairing & pairing period, Gestation Days 0, 4, 7, 11, 14, 17, 20 & Lactation Days 1 and 4
- Food consumption, Males: Weekly
Food consumption, Females: Weekly for pre-pairing period and for Gestation Days 0, 4, 7, 11, 14, 17 and 20and on Lactation Days 1 and 4 - Oestrous cyclicity (parental animals):
- not observed
- Sperm parameters (parental animals):
- not observed
- Litter observations:
- PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross abnomalies, weight gain, physical or behavioural abnormalities.
- Mortality: The numbers of live and dead pups on Day 1 of lactation and daily thereafter were determined. If possible, defects or cause of death were evaluated.
- Clinical signs: At least once daily, detailed clinical observations were made in all animals.
- Body weights: Live pups were weighed on Days 1 and 4 of lactation.
- Sex: Sex was determined for all pups on Days 1 and 4 of lactation
GROSS EXAMINATION OF DEAD PUPS
Yes, if possible, defects or cause of death were evaluated - Postmortem examinations (parental animals):
- GROSS PATHOLOGY: Yes, see below
WEIGHING OF ORGANS: Yes, see below
HISTOPATHOLOGY: Yes, see below
Terminal sacrifice
- Males: Killed on the day after the 28-day treatment period.
- Terminal sacrifice, Females (dams): Killed on Lactation Day 5-7
Gross pathology: Necropsy with tissue collection.
The number of implantation sites and corpora lutea was recorded for all dams
Organs Weights: The following organs were weighed at necropsy : testes, epididymides.
Histopathology: The following organs were microscopically observed for the control and 1000 mg/kg bw/day groups:
testes, epididymides, ovaries.
- Postmortem examinations (offspring):
- On Lactation Day 5-7 external macroscopic examination of all survivors for gross abnormalities.
- Statistics:
- The following statistical methods were used to analyze the data:
- If the variables could be assumed to follow a normal distribution, the Dunnett-test (many-to one t-test) based on a pooled variance estimate was applied for the comparison of the treated groups and the control groups for each sex.
- The Steel-test (many-to-one rank test) was applied if the data could not be assumed to follow a normal distribution.
- The Fisher Exact-test was applied to frequency data.
All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance.
Group means were calculated for continuous data and medians were calculated for discrete data
(scores) in the summary tables. Test statistics were calculated on the basis of exact values for means
and pooled variances. Individual values, means and standard deviations may have been rounded off
before printing. Therefore, two groups may display the same printed means for a given parameter, yet
display different test statistics values. - Reproductive indices:
- For each group, the following calculations were performed:
- Mating index: Number of females mated/Number of females paired x 100
- Fertility index: Number of pregnant females/Number of females paired x 100
- Conception index: Number of pregnant females/Number of females mated x 100
- Gestation index: Number of females bearing live pups/Number of pregnant females x 100
- Duration of gestation: Number of days between confirmation of mating and the beginning of parturition - Offspring viability indices:
- - Percentage live males at First Litter Check: Number of live male pups at First Litter Check/Number of live pups at First Litter Check x 100
- Percentage live females at First Litter Check: Number of live female pups at First Litter Check/Number of live pups at First Litter Check x 100
- Percentage of postnatal loss Days 0-4 of lactation: Number of dead pups on Day 4 of lactation/Number of live pups at First Litter Check x 100
- Viability index: Number of live pups on Day 4 of lactation / Number of pups born alive x 100 - Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- See 'Tables_BW_OECD421_T-1063FM.pdf' attached as background material.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- See 'Tables_food_consumption_OECD421_T-1063FM.pdf' attached as background material.
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The red foci seen macroscopically in the stomach of five high dose males correlated with minimal hemorrhage in three animals; the thickening in one animal correlated with mild inflammation.
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- no effects observed
- Description (incidence and severity):
- spermatogenic staging profiles were normal for all males examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- Mating, fertility and conception indices, precoital time, number of corpora lutea and implantation sites were unaffected by treatment. Testes and epididymis weights not affected, absence of histopathological findings in testes, epididymis and ovaries.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: NOAEL = highest dose tested. The findings in the stomachs of five high dose males were of mild severity and not considered to be adverse.
- Key result
- Critical effects observed:
- no
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: NOAEL = highest dose tested.
- Key result
- Critical effects observed:
- no
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- In this screening study there were no treatment related effects on reproduction or developmental toxicology parameters. The no-observed-adverse- effect-levels (NOAEL) for parental toxicity regarding reprotoxic endpoints and for foetal toxicity are 1000 mg/kg bw/day. The NOAEL for general parental toxicity also was derived at 1000 mg/kg bw/day.
Reference
See tables attached as background material.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subacute
- Species:
- rat
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Short description of key information:
The Reproduction/Developmental Toxicity Screening Test (OECD 421) included a reproductive toxicity-screening test, intended to provide information on possible effects on male and female reproductive performance.
Male and female Wistar rats were treated for 2 weeks pre-mating, then during the mating/postmating period, males for 28 days and females throughout gestation period, up to and including postpartum/lactation Day PPD4.
reproductive performance and indices were monitored in the parental animals, such as gonadal function, mating behaviour, conception, pregnancy, parturition and postpartum/lactation period.
Necropsy with macroscopic and detailed histological examination of reproduction organs were performed. Weights of selected organs were recorded.
There was no effect of treatment noted during evaluation of the reproductive parameters.
Effects on developmental toxicity
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guidelines for Testing of Chemicals, Guideline 421, Reproduction/Developmental Toxicity Screening Test, July 1995.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: The United States EPA Health Effects Test Guidelines, OPPTS 870.3550, Reproduction/Developmental Toxicity Screening Test, July 2000.
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Wistar rats, strain: Crl:WI(Han)
- Source: Charles River Deutschland, Sulzfeld
- Age at treatment start: approx. 12 weeks old, both sexes
- Housing in Macrolon plastic cages
during pre-pairing dosing period: In groups of 5 by sex
during pairing: 1 male+1 female/cage
males after pairing: In groups of 5
females during gestation and lactation: Females housed individually (+litter).
- Bedding material (in Macrolon plastic cages): sterilised sawdust as bedding, paper as enrichment and nesting material
- Diet (ad libitum): pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water (ad libitum): tap water
- Acclimation period: 5 days before treatment start
ENVIRONMENTAL CONDITIONS
The animal room was maintained at (target ranges for temperature and relative humidity):
- Temperature (°C): 18 - 24°C
- Relative Humidity (%): 40 - 70 %
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night
- Ventilation: at least 10 room air changes/h - Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 1% aqueous
- Details on exposure:
- - Amount (dose volume by gavage): 5 mL/kg bw/day.
Actual dose volumes were calculated accounting for the latest bodyweight.
- Frequency of preparation of dose formulations: daily within 6 hours prior to dosing
Treatment of parental animals by oral gavage administration. Test substance was not directly administered to F1 animals. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- For analysis of the test substance in the vehicle LC/MS was used with a Hypersil BDS C18 column (100 mm x 4.6 mm i.d., dp = 5 µm). The analytical method was validated. The mean contents of the test substance in dose formulations were found to be well within the acceptance limit (within +/- 15%) of dose theoretical concentration; the relative standard deviation was equal to or less than 10%.
- Details on mating procedure:
- - Male/female ratio per cage: 1/1
- Length of cohabitation: At the most 14 days, until proof of pregnancy was confirmed.
- Proof of pregnancy: Formation of vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy. - Duration of treatment / exposure:
- - Treatment period, parental males: 28 days (14 days before mating, during mating and up to the day prior to scheduled necropsy)
- Treatment period, parental females (dams): 41-54 days (from 14 days prior to mating to at least Lactation Day 4)
- Pups were not treated directly (possibly via milk): until Lactation Day 4. - Frequency of treatment:
- Once daily for 7 d/w.
- Duration of test:
- Males: 29 days
Females: 41-54 days - Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Maternal examinations:
- Clinical observations performed and frequency:
- Clinical signs: Daily (covering external appearance, motor activity & morbidity in each animal)
- Body weight, Females: Weekly for pre-pairing & pairing period, Gestation Days 0, 4, 7, 11, 14, 17, 20 & Lactation Days 1 and 4
- Food consumption, Females: Weekly for pre-pairing period and for Gestation Days 0, 4, 7, 11, 14, 17 and 20and on Lactation Days 1 and 4 - Ovaries and uterine content:
- Examinations included:
- Number of corpora lutea
- Number of implantations - Fetal examinations:
- The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross abnomalies, weight gain, physical or behavioural abnormalities.
- Mortality: The numbers of live and dead pups on Day 1 of lactation and daily thereafter were determined. If possible, defects or cause of death were evaluated.
- Clinical signs: At least once daily, detailed clinical observations were made in all animals.
- Body weights: Live pups were weighed on Days 1 and 4 of lactation.
- Sex: Sex was determined for all pups on Days 1 and 4 of lactation
GROSS EXAMINATION OF DEAD PUPS:
Yes, if possible, defects or cause of death were evaluated. - Statistics:
- The following statistical methods were used to analyze the data:
- If the variables could be assumed to follow a normal distribution, the Dunnett-test (many-to one t-test) based on a pooled variance estimate was applied for the comparison of the treated groups and the control groups for each sex.
- The Steel-test (many-to-one rank test) was applied if the data could not be assumed to follow a normal distribution.
- The Fisher Exact-test was applied to frequency data.
All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance.
Group means were calculated for continuous data and medians were calculated for discrete data
(scores) in the summary tables. Test statistics were calculated on the basis of exact values for means
and pooled variances. Individual values, means and standard deviations may have been rounded off
before printing. Therefore, two groups may display the same printed means for a given parameter, yet
display different test statistics values. - Indices:
- REPRODUCTIVE INDICES
For each group, the following calculations were performed:
- Mating index: Number of females mated/Number of females paired x 100
- Fertility index: Number of pregnant females/Number of females paired x 100
- Conception index: Number of pregnant females/Number of females mated x 100
- Gestation index: Number of females bearing live pups/Number of pregnant females x 100
- Duration of gestation: Number of days between confirmation of mating and the beginning of parturition
OFFSPRING VIABILITY INDICES
- Percentage live males at First Litter Check: Number of live male pups at First Litter Check/Number of live pups at First Litter Check x 100
- Percentage live females at First Litter Check: Number of live female pups at First Litter Check/Number of live pups at First Litter Check x 100
- Percentage of postnatal loss Days 0-4 of lactation: Number of dead pups on Day 4 of lactation/Number of live pups at First Litter Check x 100
- Viability index: Number of live pups on Day 4 of lactation / Number of pups born alive x 100 - Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: foetal toxicity
- Key result
- Abnormalities:
- not examined
- Localisation:
- other: no specific examination in this screening study; pups did not show abnormalities
- Key result
- Developmental effects observed:
- no
- Conclusions:
- In this screening study there were no treatment related effects on reproduction or developmental toxicology parameters. The no-observed-adverse- effect-levels (NOAEL) for parental toxicity regarding reprotoxic endpoints and for foetal toxicity are 1000 mg/kg bw/day. The NOAEL for general parental toxicity also was derived at 1000 mg/kg bw/day.
Reference
See tables attached as background material on pup body weight and litter size.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subacute
- Species:
- rat
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Toxicity to reproduction: other studies
Description of key information
The Reproduction/Developmental Toxicity Screening Test (OECD 421) included a developmental toxicity-screening test, intended to provide information on possible effects on the development of the F1 offspring from conception to Day 4 post-partum.
Male and female Wistar rats were treated for 2 weeks pre-mating, then during the mating/postmating period, males for 28 days and females throughout gestation period, up to and including postpartum/lactation Day PPD4. The offspring were not dosed.
The ovaries and uterine content was examined after termination of the dams on Day 5-7 post-partum. Numbers of corpora lutea, implantations and the post implantation survival were determined, gestation length was recorded.
Offspring examinations: clinical signs, body weight, body weight gain, number of live births and of viable pups per litter on postnatal Days 0 and 4, sex ratio.
There were no adverse effects on the maternal animals.
There were no adverse effects on the F1 offspring viability, clinical signs or development.
Justification for classification or non-classification
Following the results of the available studies classification of T-1063FM regarding reproductive or developmental toxicity is not warranted according to REGULATION (EC) 1272/2008.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.