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EC number: 226-603-0 | CAS number: 5435-64-3
- 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:
- supporting study
- Study period:
- 28 day study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 3,5,5-trimethylhexanal
- EC Number:
- 226-603-0
- EC Name:
- 3,5,5-trimethylhexanal
- Cas Number:
- 5435-64-3
- Molecular formula:
- C9H18O
- IUPAC Name:
- 3,5,5-trimethylhexanal
- Details on test material:
- 3,5,5-Trimethylhexanal
GLP-Reg.-No. 0637/81 762
Institute-Reg.-No. 0188
Date of production: february/march 1996
Durability: > 1 year
Purity dated 09.05.1996
- 1. 1H und 13C-NMR-spectroscopy: about 97 % Mol-%
- 2. gaschromatography: content: 91,2 mass-%
- 3. water content: 0,05 %
Expiry date: not before may 1998
Properties: clear liquid
Homogeneity: liquid is visually homogeneous
Density (20 ° C): about 0,8184 g/cm3
Solubility in water (20 ° C): < 0,1 g/l
pH: no data
Storage: room temperature, in close containers under inert gas
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Winkelmann GmbH, 33176 Borchen
- Age at study initiation: six to eight weeks
- Weight at study initiation: weight variation did not exceed +/- 20 % of the mean body weight
- Housing: Animals were housed in Makrolon type IV cages, each cage containing 5 rats.
- Diet (e.g. ad libitum): Sniff R 10 diet in pelletform (laboratory standard rat diet), food was offered ad libitum
- Water (e.g. ad libitum): The animals received tap water ad libitum
- Acclimation period: Animals were acclimatized under study conditions (except administraion of test substance) for at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° C +/- 3 ° C
- Humidity (%): 30 - 70 %
- Bedding: The bedding used was soft wood Type HW 300/500 W
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): Dosing formulations were prepared weekly. The test substance was transferred to a beaker.
- Mixing appropriate amounts with (Type of food): A corrosponding weight of corn oil, calculated for the target dosages,
was filled into the beaker and war stirred by means of magnetic stirrer for 15 minutes.
- Storage temperature of food: room temperature
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The homogeneity, the concentration and the stability of the test substance formulations were determined by Hüls Infracor GLP-Institute. Samples of all dose levels were taken repeatedly and were analyzed for concentration of the testsubstance.
- Duration of treatment / exposure:
- 28 days (27 days substitute animal No. 19 and 30)
- Frequency of treatment:
- once a day, seven days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- control
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Remarks:
- low dose
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- Remarks:
- mid dose
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Remarks:
- high dose
- No. of animals per sex per dose:
- 3 groups, each of 10 rats (five males and five females) were dosed.
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: The dose levels were chosen based on the results of a range-finding study performed at the Hüls Infracor GLP-Institute
- two female animals of the 500 mg/kg high dose group died. Therefore the highest dose was reduced to 250 mg/kg
- Post-exposure recovery period in satellite groups: 2-week recovery period in the control and high dose groups.
Examinations
- Observations and examinations performed and frequency:
- An observation of the animals for genearl health state, behavioural changes and toxicosis as well as for mortality was made twice daily, preferably in the early morning and in the late afternoon.
Once a day a clinical observation was performed, preferrable at the same time each dy and considering the peak period of anticipated effects after dosing. At weekends the animals were observed once a day about one hour after application.
Once a week in addition to the normal daily clinical observation a detailed functional observation of each animal was conducted.
In the 4th week of the dosing period an assessment of the motoractivity was performed.
Individual bodyweights were recorded at time of the allocation of animals to groups, prior to dosing on the day of commencement of treatment and subsequently at weekly intervals throughout the study. LAst recordings of bodyweights were performed at the day of necrospy.
Food consumption was measured in weekly intervals throughout the study. Mean food intake was calculated for each rat. - Sacrifice and pathology:
- Necrospy
On completion of the dosing period and recovery period animals were killed by CO2-asphyxiation and exsanguniation. A complete autoipsy including a macropathological examination was performed. - Statistics:
- Comparisons were performed between vehicle control group and low, medium and high dose groups and between the recovery control group and the high dose recovery group.
Body weights and organ weights were analysed using Kruskal Wallis non parametric analysis of variance.
Haematological data were analysed by ANOVA incorporating a Bartlett's test for homogenicity and variance.
Group means and standard deviation were calculated were appropriate.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- effects observed, treatment-related
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 250 mg/kg bw/day (nominal)
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Dose related clinical effects as piloerection and squatting/hunchback position were observed in the male and female high dose groups during the
first functional observation in the "Open filed" after application of the test substance at a dose level of 500 mg/kg/day. Two female animals of the
high dose groups died overnight and were replaced by substitutes. After reduction of the high dose to 250 mg/kg/day on the second day of the
study only individual animals of the high dose groups showed dose-related clinical signs. One female animal of the high dose group died the third day of the study most likely as a result of the application of 500 mg/kg/day the first day of the study. During the recovers period no clinical signs were observed.
High dose femals showed at the end of the treatment period also a statistically significant decrease of absolute bodyweight change (BWCHABS) and a slightly reduced group mean weekly bodyweight (BWN) were compared with control. Evidence of resersibility was found in the recovery groups.
A dose-related decrease of Triglyceride (TRIG) and Total Bilirubin (TBIL) values were observed in animals of both sexes. But apart from the TRIG-
value of the high dose female group all values were within the normal range of our historical backbround data. Evidence of reversibility was found
in the recovery groups.
Centrolobular hypertrophy (minimal slight degree) in correlation with statistically significant higher relative and absolute liver weights and focal
periportal vacuolation in treated females were considered to be substance-related. However, none of the livers examiniated showed nuclear or
cytoplasmic degenerative or necrotic changes of hepatocytes. The female group mean liver weight showed still as statistically significant increase at
the end of the recovery period. But the group mean relative liver weight of treated females showed no statistically significant difference when
compared with female high dose recovery control. It is suggested that the liver changes observed are an expression of a reversible adaptive
response of the liver to the test substnce. As such, it is generally not considered as adverse effect.
The effects caused by the test substance were more pronouned in female animals. None of the effects were irreversible. Therefore, in our
experimental conditions, the no-observed-adverse-effect level (NOAL) is 250 mg/kg/day. - Executive summary:
- s. attached background material
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