Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 201-842-3 | CAS number: 88-60-8
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well conducted study, carried out by Research Institute for Animal Science in Biochemistry and Toxicology (Japan)
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 999
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Principles of method if other than guideline:
- TC-Freetext:
*Age at study initiation: 8 week old for both sexes
*Mean weight at study initiation Dose levels(mg/kg) 0 2.5 12.5 60 Body weight (g±SD) Male 291.5±9.0 291.6±9.0 291.7±8.7 291.8±8.1 Female 220.1±7.0 220.1±7.5 219.9±6.7 220.2±7.2 No. of animals per sex per dose: 13 per sex per dose group
*Study Design
-Terminal killing: Males; day 43, Females; day 4 of lactation
-Clinical observations performed and frequency: General condition was observed once a day. Body weight and food consumption were determined once a week. Food consumption in mating period was not. Hematological and serum biochemical examinations, and urinary test were performed for all males.
-Organs examined at necropsy: Organ weight: brain, heart, liver, kidneys, spleen, thymus, adrenal glands, testes, epididymides Microscopic: control & all treated groups/ liver, spleen(female only),adrenal glands(female only), control & 60 mg/kg groups/brain, heart, kidneys,spleen, thymus, adrenal glands, testes, epididymides. - GLP compliance:
- yes
Test material
- Reference substance name:
- Automatically generated during migration to IUCLID 6, no data available
- IUPAC Name:
- Automatically generated during migration to IUCLID 6, no data available
- Details on test material:
- Produced by Sumitomo Chemical, Lot No.1271012. Purity 99.23%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Duration of treatment / exposure:
- male: 42 days,
female: from 14 days before mating to day 3 of lactation - Frequency of treatment:
- 7 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
2.5, 12.5, 60 mg/kg/day (in corn oil)
Basis:
- No. of animals per sex per dose:
- 13 per sex per dose group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: no
- Positive control:
- no data
Examinations
- Observations and examinations performed and frequency:
- -Clinical observations performed and frequency: General condition was observed once a day. Body weight and food consumption were determined once a week. Food consumption in mating period was not. Hematological and serum biochemical examinations, and urinary test were performed for all males.
- Sacrifice and pathology:
- -Terminal killing: Males; day 43, Females; day 4 of lactation
-Organs examined at necropsy: Organ weight: brain, heart, liver, kidneys, spleen, thymus, adrenal glands, testes, epididymides Microscopic: control & all treated groups/ liver, spleen(female only), adrenal glands(female only), control & 60 mg/kg groups/brain, heart, kidneys,spleen, thymus, adrenal glands, testes, epididymides. - Other examinations:
- reproductive and developmental toxicity parameters were also examined, for detail see 7.8 (toxicity to reproduction)
- Statistics:
- no data
Results and discussion
Results of examinations
- 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):
- effects observed, treatment-related
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 12.5 mg/kg bw/day (nominal)
- Sex:
- male/female
- Dose descriptor:
- LOAEL
- Effect level:
- 60 mg/kg bw/day (nominal)
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
RS-Freetext:
*LOAEL= 60 mg/kg/day, NOEL = 12.5 mg/kg/day
males : histopathological changes in liver
females: suppression of body weight gain and histopathological changes in liver
* Body weight: Suppression of body weight gain was observed at day 14 of pregnancy and day 4 of lactation in the 60 mg/kg female.
Body weight in female
Dose level(mg/kg/day) 0 2.5 12.5 60
Body weight (g, mean±SD)
day 14 of pregnancy 338.7±15.1 343.8±13.5 335.7±26.7 310.1±24.9**
Day 4 of lactation 327.4±20.9 336.5±19.9 311.8±23.9 280.1±29.8**
(**P< 0.01)
*Food consumption: Decrease in food consumption was observed lactation period in the female group at 60 mg/kg.(Statistical significant was P< 0.01 on the day 4 of
lactat ion)
*Clinical signs (description, severity, time of onset and duration): No significant effect was observed.
in the female group at 60 mg/kg.(Statistical significant was P< 0.01 on the day 4 of lactation)
*Clinical signs (description, severity, time of onset and duration): No significant effect was observed.
*Mortality and time to death: The death was not observed in any group.
*Hematology and biochemical findings: No significant effect was observed.
*Gross pathology incidence and severity: No significant effect was observed.
*Organ weight changes :
Male: Increase in absolute kidneys weight was observed in the 60 mg/kg group (P<0.05).
Female: Decrease in absolute heart and spleen weights , and increase in relative brain,liver and kidneys weights were observed in the 60 mg/kg group (P< 0.01).
*Histopathology (incidence and severity)
Male & female: Hypertrophy of centrilobular hepatocytes with eosinophilic was observed at 60 mg/kg group. Histopathological change considered to be significant
biologically was not observed in other organs.
Histopathological changes in the liver
Sex Male Female
Dose level( mg/kg/day)
0 2.5 12.5 60 0 2.5 12.5 60 Hypertrophy,eosinophilic
Hepatocyte,centrilobular
0/13 0/13 0/13 5/13* 0/13 0/13 0/13 10/13** Necrosis
2/13 1/13 1/13 1/13 4/13 2/13 1/13 6/13 Fibrosis,focal
1/13 0/13 1/13 0/13 0/13 0/13 1/13 1/13 Fatty hange,periportal
13/13 13/13 13/13 13/13 3/13 1/13 2/13 7/13
( * P< 0.05 , ** P< 0.01)
Necrosis, Fibrosis and fatty change in peripotal region are thought to be spontaneous lesion on the liver of male and female rats. Historical control incidence of fifteen Combined Repeated Dose and Reproductive/Developmental
Toxicity Studies performed at the same laboratory was checked out. The range of Necrosis, Fibrosis and Fatty change in periportal region were 0-31%, 0-23% and 0-
100%, respectively. Especially, the historical incidence of Fatty change, periportal was 100% in all of 15 studies investigated in male rats in the laboratory. In the
study of 6-tert-butyl-m-cresol, the incidence of Necrosis, focal (15% in male, 23% in female), Fibrosis, focal (8% in male, 0% in female), Fatty change, periportal (100% in male, 23% in female) in control animals falls within historical control range. Therefore, these lesions in the male and female liver of 6-tert-butyl-mcresol study were considered to be spontaneous and animals used in the study were normal.
Applicant's summary and conclusion
- Conclusions:
- Toxic effects in this study are suppression of body weight gain and increase of relative liver weight in the 60 mg/kg female, and histopathologica changes of the liver in the 60 mg/kg male and female. The NOEL is considered to be 12.5 mg/kg/day for both sexes.
- Executive summary:
method: combined repeat dose reproductive/developmental toxicity screening study according OECD TG 422
result: NOEL = 12.5 mg/kg/day (rat, male + female), LOAEL = 60 mg/kg/day (rat, male + female); Toxic effects in this study are suppression of body weight gain and increase of relative liver weight in the 60 mg/kg female, and histopathologica changes of the liver in the 60 mg/kg male and female.
reference: MHW, Japan (1999)
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.