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EC number: 203-674-6 | CAS number: 109-46-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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Endpoint summary
Administrative data
Description of key information
No repeated toxicity study was available on 1,3 -dibutylthiourea.
However two oral studies of 7 weeks in rats and mice were available in
an analogue substance: 1,3 -diethylthiourea (DETU). The aim of these
studies was to establish the maximum tolerated concentrations of DETU
for administration to dosed animals in the chronic studies. Animals were
exposed to DETU in diet during seven weeks to 147, 215, 316 and 464 ppm
for rats, and 680, 1000, 1470, 2160 and 3150 ppm for mice.
The target organ of DETU is the thyroid of rat. The LOAEL for thyroid
toxicity is 6.25 mg/kg bw in rat (= 125 ppm).
No target organ is showed in the mice.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- It's a range finding test for carcinogenicity test. In order to establish the maximum tolerated concentrations of DETU for administration to dosed animals in the chronic studies, subchronic toxicity tests were conducted.
Mice were exposed to DETU during seven weeks. - GLP compliance:
- not specified
- Limit test:
- no
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River breeding Laboratories, Inc., Wilmington, Massachussets
- Age at study initiation: around 6 weeks-old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: in polycarbonate cages suspended from aluminium racks.
- Diet (e.g. ad libitum): Wayne Lab-Blox (Allied Mills, Inc. Chicago, Ill.), ad libitum
- Water (e.g. ad libitum): aciduled water (pH 2.5) was suplied to animals in water bottles filled in an automated metering device, ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26°C
- Humidity (%):45-55%
- Air changes (per hr):12-15
- Photoperiod (hrs dark / hrs light): fluorescent lighlting 8h/day (9.00 am to 5.00 pm) - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- no
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 7 weeks
- Frequency of treatment:
- daily
- Dose / conc.:
- 680 ppm
- Dose / conc.:
- 1 000 ppm
- Dose / conc.:
- 1 470 ppm
- Dose / conc.:
- 2 160 ppm
- Dose / conc.:
- 3 150 ppm
- No. of animals per sex per dose:
- 5 males + 5 females per dose
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Post-exposure period: 1 week
- Positive control:
- no
- Observations and examinations performed and frequency:
- Individual body weights and food consumption data were recorded twice weekly throughout the study.
- Sacrifice and pathology:
- Upon termination of the study, all survivors were sacrified and necropsied.
- Other examinations:
- no
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Details on results:
- At 680 ppm, the mean body weight gain was decreased among males (-10%) and females (-8%) compared to control group.
=> The high concentration selected for administration to dosed mice in the main study was 500 ppm. - Dose descriptor:
- other: maximum tolerated dose
- Effect level:
- 500 ppm
- Basis for effect level:
- other: 500 ppm x 0.05 (assumed rodent food consymption per bw) = 25 mg/kg bw/d
- Dose descriptor:
- NOAEL
- Effect level:
- 500 ppm
- Basis for effect level:
- other: No effects were observed at 500 ppm. 500 ppm x 0.05 = 25 mg/kg bw/d
- Critical effects observed:
- no
- Conclusions:
- According to this study, the maximum tolerated concentration was 500 ppm of DETU in diet for the mice.
- Executive summary:
It's a range finding test for carcinogenicity test. In order to establish the maximum tolerated concentrations of DETU for administration to dosed animals in the chronic studies, subchronic toxicity tests were conducted.
Mice were exposed to DETU during seven weeks to 680, 1000, 1470, 2160 and 3150 ppm in diet.
At 680 ppm, the mean body weight gain was decreased among males (-10%) and females (-8%) compared to control group.
=> The high concentration selected for administration to dosed mice in the main study was 500 ppm.
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- It's a range finding test for carcinogenicity test. In order to establish the maximum tolerated concentrations of DETU for administration to dosed animals in the chronic studies, subchronic toxicity tests were conducted.
Rats were exposed to DETU during seven weeks. - GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Frederick Cancer Research Center, Frederick, Maryland.
- Age at study initiation: around 6 weeks-old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: in polycarbonate cages suspended from aluminium racks.
- Diet (e.g. ad libitum): Wayne Lab-Blox (Allied Mills, Inc. Chicago, Ill.), ad libitum
- Water (e.g. ad libitum): aciduled water (pH 2.5) was suplied to animals in water bottles filled in an automated metering device, ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26°C
- Humidity (%):45-55%
- Air changes (per hr):12-15
- Photoperiod (hrs dark / hrs light): fluorescent lighlting 8h/day (9.00 am to 5.00 pm) - Route of administration:
- oral: feed
- Duration of treatment / exposure:
- 7 weeks
- Frequency of treatment:
- daily
- Dose / conc.:
- 147 ppm
- Dose / conc.:
- 215 ppm
- Dose / conc.:
- 316 ppm
- Dose / conc.:
- 464 ppm
- No. of animals per sex per dose:
- 5 males + 5 females per dose
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Post-exposure period: 1 week
- Positive control:
- no
- Observations and examinations performed and frequency:
- Individual body weights and food consumption data were recorded twice weekly throughout the study.
- Sacrifice and pathology:
- Upon termination of the study, all survivors were sacrified and necropsied.
- Other examinations:
- no
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Details on results:
- - At 316 ppm concentration: Mean body weight gain increased by 3 % among male rats compared to control group while it decreased by 11% in female rats. 1 female rat died and another had an arched back and rough coat.
- At 215 ppm concentration: Mean body weight gain decreased by 10 % among male rats compared to control group while it decreased by 1% in female rats.
=> The maximum tolerated concentration was around 250 ppm. - Key result
- Dose descriptor:
- other: Maximum tolerated dose
- Effect level:
- 250 ppm
- Sex:
- male/female
- Basis for effect level:
- other: 250 ppm x 0.05 (assumed rat food consumption per bw) = 12.5 mg/kg bw/d
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 147 ppm
- Sex:
- male/female
- Basis for effect level:
- other: Changes of bw were observed at 215 and 316 ppm. 147 ppm x 0.05 = 7.35 mg/kg bw
- Critical effects observed:
- no
- Conclusions:
- According to this study, the maximum tolerated concentration was 250 ppm of DETU in diet for the rats.
- Executive summary:
It's a range finding test for carcinogenicity test. In order to establish the maximum tolerated concentrations of DETU for administration to dosed animals in the chronic studies, subchronic toxicity tests were conducted. Rats were exposed to DETU in diet during seven weeks to 147, 215, 316 and 464 ppm.
- At 316 ppm concentration: Mean body weight gain increased by 3 % among male rats compared to control group while it decreased by 11% in female rats. 1 female rat died and another had an arched back and rough coat.
- At 215 ppm concentration: Mean body weight gain decreased by 10 % among male rats compared to control group while it decreased by 1% in female rats.
=> The maximum tolerated concentration was around 250 ppm.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 6.25 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Reliable study (klimish score of 2)
- System:
- endocrine system
- Organ:
- thyroid gland
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
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
7 -weeks study in rats and mice on analogue substance (1979):
Rats were exposed to DETU in diet during seven weeks to 147, 215, 316 and 464 ppm.
- At 316 ppm concentration: Mean body weight gain increased by 3 % among male rats compared to control group while it decreased by 11% in female rats. 1 female rat died and another had an arched back and rough coat.
- At 215 ppm concentration: Mean body weight gain decreased by 10 % among male rats compared to control group while it decreased by 1% in female rats.
=> The maximum tolerated concentration was around 250 ppm, and the NOAEL is 147 ppm (7.35 mg/kg bw/d).
Mice were exposed to DETU during seven weeks to 680, 1000, 1470, 2160 and 3150 ppm in diet.
At 680 ppm, the mean body weight gain was decreased among males (-10%) and females (-8%) compared to control group.
=> The high concentration selected for administration to dosed mice in the main study was 500 ppm (=NOAEL).
Carcinogenicity tests on rats and mice.
Rats were exposed to DETU in diet during 103 weeks at 125 and 250 ppm (6.25 and 12.50 mg/kg bw/d respectively).
No mortality, no clinical signs and no change of body weight gain were observed during this study.
This study shows that thyroid is a target organ of DETU at the higher dose (250 ppm). A relatively high incidence of thyroid tumors (in particular thyroid follicular-cell carcinomas and follicular-cell adenomas) was noted and appeared to be related to the dietary administration of N,N'-diethylthiourea.The LOAEL for carcinogenicity and thyroid toxicity is 125 ppm (6.25 mg.kg bw/d).
Mice were exposed to DETU in diet during 103 weeks at 250 and 500 ppm (12.5 and 25 mg/kg bw/d respectively).
No mortality, no clinical signs were observed during this study, but decrease of body weight gain was observed at each dose.
No effects on thyroid were observed in this study at any dose.
The NOAEL for general toxicity is smaller than 12.5 mg/kg bw/d.
Study of Astwood (1945) : Effects of DETU on thyroid function (section 7.9.3.)
DETU was tested in rats for capacity to interfere with the endocrine function of the thyroid gland. Test substance was administered to young rats by mixing it with the food at 37 mg/kg bw. At the end of ten days the thyroid glands were examined grossly and microscopically, and the relative activities of the compounds were then roughly compared on the basis on the minimal dose required to produce a noticeable effect.
The weight of thyroid was increased in rat treated with DETU compared to control rats. Thyroid iodine concentration in treated rats was smaller than concentration of control rats. Therefore, an antithyroid activity of DETU was observed in the rats treated with DETU compared to the control rats (treated with thiouracil) at 37 mg/kg bw.
Justification for classification or non-classification
Based on the available data, 1,3 -dibutylthiourea should be classified for repeated toxicity according to the Regulation EC.N°1272/2008 : STOT RE 1 (thyroid) - H372 "Causes damage to organs through prolonged or repeated exposure".
Justification: the LOAEL for thyroid toxicity (hyperplasia, antithyroid activity) is 6.25 mg/kg bw/d (<10 mg/kg bw/d).
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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