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EC number: 224-929-8 | CAS number: 4559-86-8
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
The NOAEL of 27 mg/cm2 was calculated from an applied dose of 110 mg/kg bw/d, which has been distributed over a surface area of approximately 4 cm2.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1979-1980
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Crl:CD(SD)BR
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Source: Charles River Breeding Laboratories, Inc., North Wilmington, MA
Housing: individually
Diet: ad libitum
Water: ad libitum
Acclimation period: ca. 2 days
ENVIRONMENTAL CONDITIONS
Temperature (°C): 24 +/- 4
Humidity (%): 50 +/- 20
Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- not specified
- Vehicle:
- other: Dimethyl phthalate
- Details on exposure:
- Rats were grouped on gestation days 3 and 4 so that group mean body weights were similar. Three groups, each of 27 rats, were treated dermally with ca. 0, 110, 225 or 475 mg/kg bw/d. Rats were treated once daily from day 6 to day 15 of gestation. Doses were delivered as the appropriate concentration of 1,1,3,3-tetrabutylurea in 0.5 ml dimethyl phthalate. For the low-, intermediate- and high-dose groups, the concentrations of 1,1,3,3-tetrabutylurea in dimethyl phthalate were 5, 10 and 20% (v/v), respectively. Daily applications were made to the clipped intact skin of the back, and hair was removed by clipping whenever necessary during the 10-day dosing period. Each dose of 1,1,3,3-tetrabutylurea or dimethyl phthalate was delivered by a separate pipette; the last drop was touched off and the liquid was gently distributed over a surface area of approximately 4 cm2.
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Rats were treated once daily from days 6 to 15 of gestation, i.e. 10 days
- Frequency of treatment:
- once daily
- Remarks:
- Doses / Concentrations:
ca. 0, 110, 225 or 475 mg/kg bw/d
Basis: - No. of animals per sex per dose:
- Number of pregnant rats per group: 24, 24, 22 and 18
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Dose levels were selected following pilot studies
- Observations and examinations performed and frequency:
- Rats were weighed five times during gestation and observations for clinical signs were made daily. On day 21 of gestation, each rat was killed by chloroform inhalation. The uterus was removed, weighed and opened and the foetuses were separated from the uterine wall and examined. The number of corpora lutea in each ovary, the number of implantation sites in each uterine horn and the numbers and locations of all live and dead foetuses and resorptions were recorded. The uterus and ovaries of each rat were examined for gross changes and preserved, while other tissues and organs were examined grossly and discarded if found to be normal.
- Sacrifice and pathology:
- study was terminated on day 21 of gestation
- Statistics:
- Fisher's exact probability test, analyses of variance and least significant difference tests, Mann-Whitney U test
- Clinical signs:
- no effects observed
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- All rats survived the entire test period. No abnormal clinical signs were observed among rats receiving either solvent control or 110 mg/kg bw. In rats receiving 225 mg/kg bw, mild to moderate skin irritation was observed at the application site, generally after two to five doses. Moderate skin irritation after two to five doses and fissuring after five to eight doses was seen in most rats treated with 475 mg/kg bw. No other unusual clinical signs were seen in the rats treated at the two highest dose levels. Body-weight gain over days 6-16 was markedly reduced in rats receiving 475 mg/kg bw. It was moderately reduced during the treatment period in the 225 mg/kg bw group, but had recovered somewhat by day 21. Body-weight gain was only slightly depressed during the treatment period at 110 mg/kg bw (81, 71, 60 or 25 g, respectively). The examination of different tissues and organs (not further specified) gave no indication for adverse effects.
- Dose descriptor:
- NOAEL
- Effect level:
- 110 mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- other: Skin irritation and a reduction in maternal bodyweight gains
- Critical effects observed:
- not specified
- Conclusions:
- In dosed rats no adverse effects were seen at a dose level of 110 mg/kg bw
- Executive summary:
In a study focussed on developmental toxicity and teratogenicity, female rats were dosed dermally with 0, 110, 225 or 475 mg/kg bw once daily over 10 days. At 110 mg/kg bw no adverse effects were observed (NOAEL), while at the higher doses skin irritation and a reduction in bodyweight gains was seen. The examination of different tissues and organs (not further specified) gave no indication for adverse effects.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 110 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1979-1980
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Crl:CD(SD)BR
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Source: Charles River Breeding Laboratories, Inc., North Wilmington, MA
Housing: individually
Diet: ad libitum
Water: ad libitum
Acclimation period: ca. 2 days
ENVIRONMENTAL CONDITIONS
Temperature (°C): 24 +/- 4
Humidity (%): 50 +/- 20
Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- not specified
- Vehicle:
- other: Dimethyl phthalate
- Details on exposure:
- Rats were grouped on gestation days 3 and 4 so that group mean body weights were similar. Three groups, each of 27 rats, were treated dermally with ca. 0, 110, 225 or 475 mg/kg bw/d. Rats were treated once daily from day 6 to day 15 of gestation. Doses were delivered as the appropriate concentration of 1,1,3,3-tetrabutylurea in 0.5 ml dimethyl phthalate. For the low-, intermediate- and high-dose groups, the concentrations of 1,1,3,3-tetrabutylurea in dimethyl phthalate were 5, 10 and 20% (v/v), respectively. Daily applications were made to the clipped intact skin of the back, and hair was removed by clipping whenever necessary during the 10-day dosing period. Each dose of 1,1,3,3-tetrabutylurea or dimethyl phthalate was delivered by a separate pipette; the last drop was touched off and the liquid was gently distributed over a surface area of approximately 4 cm2.
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Rats were treated once daily from days 6 to 15 of gestation, i.e. 10 days
- Frequency of treatment:
- once daily
- Remarks:
- Doses / Concentrations:
ca. 0, 110, 225 or 475 mg/kg bw/d
Basis: - No. of animals per sex per dose:
- Number of pregnant rats per group: 24, 24, 22 and 18
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Dose levels were selected following pilot studies
- Observations and examinations performed and frequency:
- Rats were weighed five times during gestation and observations for clinical signs were made daily. On day 21 of gestation, each rat was killed by chloroform inhalation. The uterus was removed, weighed and opened and the foetuses were separated from the uterine wall and examined. The number of corpora lutea in each ovary, the number of implantation sites in each uterine horn and the numbers and locations of all live and dead foetuses and resorptions were recorded. The uterus and ovaries of each rat were examined for gross changes and preserved, while other tissues and organs were examined grossly and discarded if found to be normal.
- Sacrifice and pathology:
- study was terminated on day 21 of gestation
- Statistics:
- Fisher's exact probability test, analyses of variance and least significant difference tests, Mann-Whitney U test
- Clinical signs:
- no effects observed
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- All rats survived the entire test period. No abnormal clinical signs were observed among rats receiving either solvent control or 110 mg/kg bw. In rats receiving 225 mg/kg bw, mild to moderate skin irritation was observed at the application site, generally after two to five doses. Moderate skin irritation after two to five doses and fissuring after five to eight doses was seen in most rats treated with 475 mg/kg bw. No other unusual clinical signs were seen in the rats treated at the two highest dose levels. Body-weight gain over days 6-16 was markedly reduced in rats receiving 475 mg/kg bw. It was moderately reduced during the treatment period in the 225 mg/kg bw group, but had recovered somewhat by day 21. Body-weight gain was only slightly depressed during the treatment period at 110 mg/kg bw (81, 71, 60 or 25 g, respectively). The examination of different tissues and organs (not further specified) gave no indication for adverse effects.
- Dose descriptor:
- NOAEL
- Effect level:
- 110 mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- other: Skin irritation and a reduction in maternal bodyweight gains
- Critical effects observed:
- not specified
- Conclusions:
- In dosed rats no adverse effects were seen at a dose level of 110 mg/kg bw
- Executive summary:
In a study focussed on developmental toxicity and teratogenicity, female rats were dosed dermally with 0, 110, 225 or 475 mg/kg bw once daily over 10 days. At 110 mg/kg bw no adverse effects were observed (NOAEL), while at the higher doses skin irritation and a reduction in bodyweight gains was seen. The examination of different tissues and organs (not further specified) gave no indication for adverse effects.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 27 mg/cm²
- Study duration:
- subacute
- Species:
- rat
Additional information
In a study focussed on developmental toxicity and teratogenicity, female rats were dosed dermally with 0, 110, 225 or 475 mg/kg bw once daily over 10 days. At 110 mg/kg bw no adverse effects were observed (NOAEL), while at the higher doses skin irritation and a reduction in bodyweight gains was seen. The examination of different tissues and organs (not further specified) gave no indication for adverse effects.
In an older study with male rabbits, which cannot finally be evaluated (original reference not available), the dermal application of 1500 mg/kg bw on 6 h per day over 10 days (applied as 40% solution in dimethyl phthalate) caused no mortality. Apart from weight loss and skin irritation no other effects were reported.
Justification for classification or non-classification
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.
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