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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 800-433-2 | CAS number: 1016636-76-2
- 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
Endpoint summary
Administrative data
Description of key information
A 7-day repeated dose study (Dunster J S, 2013) is available which is key study. The oral NOEL value of test substance is considered to be 1000 mg/kg bw/day.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 29 May to 09 October 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study run to a method comparable with current guidelines and to GLP
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent
- Age at study initiation: approximately nine weeks old
- Weight at study initiation: the males weighed 361 to 387g, the females weighed 242 to 278g
- Housing: in groups of three by sex in solid floor polypropylene cages with stainless steel mesh lids and furnished with softwood flakes (Datesand Ltd., Cheshire, UK).
- Diet (e.g. ad libitum): free access to food(Rodent 2014C Teklad Global Certified Diet, Harlan Laboratories UK, Oxon, UK)
- Water (e.g. ad libitum): free access to water
- Acclimation period: six days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 15%
- Air changes (per hr): at least fifteen air changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light and twelve hours darkness
IN-LIFE DATES: From 8 June to 25 June 2013 - Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: The test item was prepared at the appropriate concentrations as a suspension in Arachis oil BP.
VEHICLE
- Concentration in vehicle: 37.5, 125, 250 mg/mL
- Amount of vehicle (if gavage): 4 mL/kg - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- seven consecutive days
- Frequency of treatment:
- daily
- Remarks:
- Doses / Concentrations:
150, 500, 1000 mg/kg bw/day
Basis:
actual ingested - No. of animals per sex per dose:
- 3
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on the results of previous toxicity work (Harlan Laboratories Ltd., Study Number 41300893)
No additional information - Positive control:
- No data
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All animals were examined for overt signs of toxicity, ill-health or behavioural change immediately before dosing, immediately post dosing and one hour after dosing.
BODY WEIGHT: Yes
- Time schedule for examinations: Individual body weights were recorded on Day 1, 4 and 8.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption was recorded for each cage group for study Days 1 to 4 and Days 4 to 8.
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: daily
OPHTHALMOSCOPIC EXAMINATION: No Data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the study (Day 7).
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: all animals from each test and control group
- Parameters [Haemoglobin (Hb), Erythrocyte count (RBC), Haematocrit (Hct), Erythrocyte indices - mean corpuscular haemoglobin (MCH), - mean corpuscular volume (MCV), - mean corpuscular haemoglobin concentration (MCHC), Total leucocyte count (WBC), Differential leucocyte count - neutrophils (Neut), - lymphocytes (Lymph), - monocytes (Mono), - eosinophils (Eos), - basophils (Bas), Platelet count (PLT), Prothrombin time (CT)] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the study (Day 7).
- Animals fasted: No
- How many animals: all animals from each test and control group
- Parameters [Urea Calcium (Ca++), Glucose Inorganic phosphorus (P), Total protein (Tot.Prot.), Aspartate aminotransferase (ASAT), Albumin Alanine aminotransferase (ALAT), Albumin/Globulin (A/G) ratio (by calculation), Alkaline phosphatase (AP), Sodium (Na+) Creatinine (Creat), Potassium (K+), Total cholesterol (Chol),Chloride (Cl-), Total bilirubin (Bili), Triglycerides (Tri)] were examined.
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data
No additional information - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (On completion of the dosing period all surviving animals were killed by intravenous overdose of sodium pentobarbitone followed by exsanguination. All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded.)
HISTOPATHOLOGY: Yes (All tissues were despatched to the histology processing Test Site Propath UK Ltd. for processing (Principal Investigator: N Fower). Tissues from all control and 1000 mg/kg bw/day dose group animals were prepared as paraffin blocks, sectioned at a nominal thickness of 5 μm and stained with haematoxylin and eosin for subsequent microscopic examination. Any macroscopically observed lesions were also processed together with the liver and spleen from all 150 and 500 mg/kg bw/day dose group animals.) - Other examinations:
- The following organs, removed from animals that were killed at the end of the study, were dissected free from fat and weighed before fixation: Adrenals, Ovaries, Brain, Spleen, Epididymides, Testes, Heart, Thymus, Kidneys, Uterus, Liver.
- Statistics:
- Where considered appropriate, quantitative data was subjected to statistical analysis to detect the significance of intergroup differences from control; statistical significance was achieved at a level of p<0.05. Statistical analysis was performed on the following parameters:
Body Weight Change, Haematology, Blood Chemistry, Absolute Organ Weights, Body Weight-Relative Organ Weights.
Data were analysed using the decision tree from the ProvantisTM Tables and Statistics Module as detailed as follows:
Where appropriate, data transformations were performed using the most suitable method. The homogeneity of variance from mean values was analysed using Bartlett’s test. Intergroup variance were assessed using suitable ANOVA, or if required, ANCOVA with appropriate covarities. Any transformed data were analysed to find the lowest treatment level that showed a significant effect using the Williams Test for parametric data or the Shirley Test for nonparametric data. If no dose response was found but the data shows non-homogeneity of means, the data were analysed by a stepwise Dunnett’s (parametric) or Steel (non-parametric) test to determine significant difference from the control group. Where the data were unsuitable for these analyses, pair-wise tests was performed using the Student t-test (parametric) or the Mann-Whitney U test (non-parametric).
Probability values (p) are presented as follows:
p<0.01 **
p<0.05 *
p≥0.05 (not significant) - Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY:
There were no clinically observable signs of toxicity.
One male treated with 1000 mg/kg bw/day showed clinical signs of tiptoe gait, staining around the snout, decreased respiratory rate, pilo-erection, lethargy and hunched posture on Day 2. This animal was subsequently terminated on the same day. This death was attributable to inappropriate dosing technique and was considered unrelated to systemic toxicity.
One female treated with 1000 mg/kg bw/day and one female treated with 500 mg/kg bw/day showed increased salivation on either Day 6 or Day 7 only. Observations of this nature are commonly observed following oral administration of an unpalatable test item formulation and in isolation are considered not to be of toxicological significance.
There were no unscheduled deaths related to treatment with the test item.
One male treated with 1000 mg/kg bw/day was killed in extremis following severe clinical signs on Day 2. This death was attributable to inappropriate dosing technique and was considered unrelated to systemic toxicity.
BODY WEIGHT AND WEIGHT GAIN:
There were no adverse effects on body weight change detected for treated animals when compared to controls.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
There were no adverse effects on dietary intake for treated animals when compared to controls.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study):
Daily visual inspection of water bottles did not reveal any overt intergroup differences in water intake.
HAEMATOLOGY:
There were no toxicologically significant effects detected in the haematological parameters investigated.
Males treated with 1000 and 500 mg/kg bw/day showed a statistically significant (p<0.05) reduction in mean corpuscular volume. All individual values were within normal ranges for rats of the strain and age used, therefore the intergroup differences were considered not to be of toxicological importance.
CLINICAL CHEMISTRY:
There were no toxicologically significant effects detected in the blood chemical parameters investigated.
Females treated with 1000 and 500 mg/kg bw/day showed a statistically significant (p<0.05) increase in inorganic phosphorus. All individual values were within normal ranges for rats of the strain and age used, therefore the intergroup differences were considered not to be of toxicological importance. Females treated with 500 mg/kg bw/day also showed a statistically significant (p<0.05) increase in sodium concentration. All individual values were within normal ranges for rats of the strain and age used and in the absence of a similar effect at 1000 mg/kg bw/day the intergroup difference was considered not to be of toxicological importance.
ORGAN WEIGHTS:
There were no treatment-related changes detected in the organ weights recorded.
GROSS PATHOLOGY:
There were no treatment-related macroscopic abnormalities detected.
The interim death animal showed gaseous distension of the small and large intestines, a fluid filled thoracic cavity and a hole present in the oesophagus. This death was most probably attributable to inappropriate dosing technique. One control female showed the left horn of the uterus in two parts (detached from one another). In the absence of treatment this was considered to be a congenital abnormality.
HISTOPATHOLOGY: NON-NEOPLASTIC
There were no treatment-related microscopic abnormalities detected. - Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Critical effects observed:
- not specified
- Conclusions:
- The oral administration of the test substance to rats by gavage, at dose levels of 150, 500 and 1000 mg/kg bw/day, did not result in any toxicologically significant effects. The ‘No Observed Effect Level’ (NOEL) was therefore considered to be 1000 mg/kg bw/day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- 1 (reliable without restriction)
Additional information
A 7-day repeated dose study was conducted according to OECD 407 using rats (Dunster J S, 2013). Key study.
It is considered that the test substance did not result in any toxicologically significant effects when administered to rats by daily oral gavage for a period of up to 7 consecutive days at 150, 500 and 1000 mg/kg bw/day. The "No Observed Effect Level" (NOEL) was therefore considered to be 1000 mg/kg bw/day.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
This study was conducted according to OECD 407 using rat.
Justification for classification or non-classification
Repeated dose toxicity: A 7-day repeated dose study on rats showed that the test substance did not result in any toxicologically significant effects when administered to rats by daily oral gavage for a period of up to 7 consecutive days at 150, 500 and 1000 mg/kg bw/day, resulted a NOEL value 1000 mg/kg bw/day.
Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.9.3 the test substance is not classfied for repeated dose toxicity endpoint.
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.