Registration Dossier
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: 203-929-1 | CAS number: 112-03-8
- 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:
- sub-chronic toxicity: oral
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- From October 29, 2001 to June 18, 2002
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- RA study
- Justification for type of information:
- Refer to the section 13 for details on the read across justification. The repeated dose toxicity (oral) study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Quaternary ammonium compounds, coco alkyltrimethyl, chlorides
- EC Number:
- 263-038-9
- EC Name:
- Quaternary ammonium compounds, coco alkyltrimethyl, chlorides
- Cas Number:
- 61789-18-2
- Molecular formula:
- C15 H34 Cl1 N1
- IUPAC Name:
- Quaternary ammonium compounds, C12-C18 (even numbered) alkyltrimethyl chloride
Constituent 1
- Specific details on test material used for the study:
- - Physical state: Pale straw coloured liquid
- Analytical purity: 35.5% coco alkyl trimethyl ammonium chloride, 64.5% water
- Lot/batch No.: RHO20010082
- Storage condition of test material: Room temperature, in the dark
Test animals
- Species:
- rat
- Strain:
- other: Sprague-Dawley, Crl:CD® (SD) IGS BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Charles River (UK) limited, Margate, Kent
- Age at study initiation: 6 wk
- Weight at study initiation: Males: 141-183g, females: 132-161g
- Acclimation period: 14d
ENVIRONMENTAL CONDITIONS
- Temperature: 21±2°C
- Humidity: 55±15%
- Photoperiod (hrs dark / hrs light): 12h/12h
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: mixed with diet
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Mean dietary admixture concentrations were within acceptable limits for the purpose of the study (Gas chromatography).
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Daily in feed
Doses / concentrations
- Remarks:
- Doses / Concentrations: 0, 100, 500 and 2000 ppm (equivalent to 22, 113 and 273 mg/kg bw/day after correction of 35.5% purity); the highest dose of 2000 ppm was reduced to 1000 ppm from Day 29 onwards due to deterioration in health of treated animals at 2000 ppm.
Basis: nominal in diet
- No. of animals per sex per dose:
- 10 males and 10 females per dose
- Control animals:
- yes, plain diet
- Details on study design:
- - Post-exposure recovery period in satellite groups: None
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily
BODY WEIGHT: Yes
- Time schedule for examinations: Day 0 (the day before start of treatment) and weekly thereafter
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Weekly throughout the study
FOOD EFFICIENCY: Yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: daily for each cage group
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Before start of treatment and before termination of treatment (during week 12)
- Dose groups that were examined: All
HAEMATOLOGY: Yes
- Time schedule for collection of blood: End of treatment (Day 90)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: End of treatment (Day 90)
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Day 0 (the day before start of treatment) and weekly thereafter
- Dose groups that were examined: All
- Battery of functions tested: Sensory activity - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, all animals
HISTOPATHOLOGY: Yes, Macroscopic lesions, Adrenals, Aorta, Bone and bone marrow (femur including stifle joint), Bone and bone marrow (sternum), Brain (including cerebrum, cerebellum and pons), Cecum, Colon, Duodenum, Epididymides, Eyes, Gross lesions, Heart, ileum, Jejunum, Kidneys, Liver, Lungs (with bronchi), Lymph nodes (cervical and mesenteric), Mammary gland, Muscle (skeletal), Oesophagus, Ovaries, Pancreas, Pituitary gland, Prostate, Rectum, Salivary glands (submaxillary), Sciatic nerve, Seminal vesicles, Skin (hind limb), Spinal cord (cervical), Spleen, Stomach, Testes, Thymus, Thyroid/parathyroid, Tongue, Trachea, Urinary bladder, Uterus. - Statistics:
- Data were processed to give group mean values and standard deviation where appropriate. Haematological, blood chemical, organ weight, weekly body weight gain and quantitative functional performance and sensory reactivity data were assessed for control and test substance treatment groups for dose response relationship by linear regression analysis, followed by one way analysis of variance (ANOVA) incorporating Levene's test for homogeneity of variance. Where variances were shown to be homogenous, pairwise comparisons were conducted using Dunnett's test. Where Levene's test showed unequal variances, the data were analysed using non-parametric methods: Kruskal-Wallis ANOVA and Mann-Whitney 'U' test.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- High dose animals developed clinical signs of toxicity from Day 7 onwards. These included hunched posture, pilo-erection, tiptoe gait, diarrhoea and red/brown staining of external body surface. Due to these effects, the dose level was reduced to 1000 ppm from Day 29 onwards. Clinical signs persisted following the reduction in dose level and included two incidents of pallor of extremities together with generalised fur loss. No clinically observable signs of toxicity were detected at the mid and the high doses.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred during the study period.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced body weight gain was detected for high dose animals of either sex during the first five weeks of the study compared with controls. Mid dose males were similarly affected but this was confined to week 1 and 2 only. Body weight gain recovered following reduction in the dose level and was comparable with controls thereafter but terminal bodyweights for high dose animals and mid dose males remained lower than controls. No adverse effect on bodyweight gain was detected for 500 ppm females or for animals of either sex treated with the low dose.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced food intake was observed in the high and mid dose animals throughout the study period compared with controls.
- Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- Food efficiency was reduced over the first three weeks of the study but this was confined to the high dose group only. No adverse effect on dietary intake or food efficiency was detected at the low dose.
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- No appreciable intergroup differences were detected. High dose animals showed a reduced water intake on Day 6 of the study which recovered thereafter.
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- - Detailed open-field observations conducted during the study confirmed the clinical signs of hunched posture, pilo-erection and tiptoe gait detected in high dose animals. No such effects were detected at the mid or low dose levels.
- Functional performance test: No treatment-related changes were detected.
- Sensory Reactivity Assessments: High dose females showed an increase in startle reflex parameters compared with controls. No such effects were detected for high dose males or for animals of either sex treated with the lower doses. - Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- No toxicologically important organ weight changes were detected. The reductions in absolute weight (including heart, kidneys, liver and thymus weight at the high dose and heart weight at the mid dose) and increases in relative weight (including high dose brain epididymides, kidneys, spleen, testes and ovaries weight), were all considered to be a result of reduced bodyweight development rather than test substance toxicity.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related macroscopic abnormalities.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Treatment-related changes were observed in the spleen and kidneys. Lower severities of pigment accumulation were observed in the spleen of high dose male rats but not for the females (p <0.05). A higher incidence of pigment accumulation was observed in the kidneys of the high and mid dose male rats. In both tissues the pigment reacted positively to Perl's staining technique and was considered to be haemosiderin.
- Histopathological findings: neoplastic:
- not specified
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 22 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: effects observed at 113 and 273 mg/kg bw/day
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 113 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food efficiency
- histopathology: non-neoplastic
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 273 mg/kg bw/day (actual dose received)
- System:
- other: microscopic changes in the spleen and kidneys of high dose animals
- Organ:
- kidney
- spleen
- Treatment related:
- yes
- Dose response relationship:
- yes
Applicant's summary and conclusion
- Conclusions:
- - Based on the results of the read across study, dietary administration of the test substance to rats for a period of 90 days at levels up to 273 mg ai.i/kg bw/day resulted in toxicologically significant effects at the high dose and marginal effects at the next lower dose of 113 mg ai.i/kg bw/day. No such effects were demonstrated at the lowest dose of 22 mg a.i./kg bw/day. Therefore, the NOEL was considered to be 22 mg a.i./kg bw/day.
(The changes observed at the mid dose were considered to be minor, isolated effects associated with the reduced palatability of the test substance and were considered not to represent an adverse health effect. Hence, for the purposes of hazard evaluation, the NOAEL should be regarded as 113 mg/kg bw/day.) - Executive summary:
A study was conducted to determine the oral repeated dose toxicity of the read across substance, quaternary ammonium compounds, C12-C18 (even numbered) alkyltrimethyl chloride (C12-18 TMAC), according to OECD Guideline 408 and EU Method B.26, in compliance with GLP. Sprague-Dawley rats were administered the test substance at concentrations of 0, 100, 500 or 2000 ppm, corresponding to 22, 113 and 273 mg a.i./kg bw/day) in the diet for 90 d. The highest dose of 2000 ppm was reduced to 1000 ppm from Day 29 onwards due to deterioration in health of the test animals at 2000 ppm. At the highest dose, the treatment-related findings were clinical signs of toxicity, reduced body weight gain and food efficiency, organ weight changes and microscopic changes in the spleen and kidneys. At the mid dose, reduced body weight gain (males) and reduced food consumption, reduced absolute heart weight and higher incidence of haemosiderin accumulation in the kidneys of males was observed. No treatment-related effects were observed at the lowest dose. Hence, the NOEL was considered to be 100 ppm (i.e. equivalent to 22 mg a.i./kg bw/day). The changes observed at 500 ppm were considered to be minor, isolated effects associated with the reduced palatability of the test substance and were considered not to represent an adverse health effect. The NOAEL was therefore 500 ppm (i.e. equivalent to 113 mg a.i./kg bw/day) (Jones, 2002).
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.

Route: .live1