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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 601-595-5 | CAS number: 119302-20-4
- 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
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:
- 7 October 1999 to 29 February 2000
- Reliability:
- 1 (reliable without restriction)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- GLP compliance:
- yes
- Species:
- rat
- Strain:
- other: Wistar Crl:(WI) BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld Germany
- Age at study initiation: Approx. 6 weeks
- Weight at study initiation: +/- 20% of the sex mean.
- Housing: Group housing of 5 animals per sex per cage in stainless steel suspended cages with wire mesh floors. During activity monitoring, individually housed over night in Macrolon plastic cages with sterilised sawdust (SAWI, Jelu Werk, Rosenberg, Germany).
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (Carfil Quality BVBA, Oud-Turnhout, Belgium).
- Water (e.g. ad libitum): Free access to tap-water.
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21˚C +/- 3˚
- Humidity (%): 30-70%
- Air changes (per hr): Approximately 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours artificial light/12 hours dark
IN-LIFE DATES: From: 7 October 1999 To: 4 November 1999 - Route of administration:
- oral: gavage
- Vehicle:
- propylene glycol
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Formulations (w/w) were prepared daily within 4 hours prior to dosing. Adjustment was made for specific gravity of vehicle.
VEHICLE
- Justification for use and choice of vehicle (if other than water): Based on trial formulations performed at NOTOX and confirmed to be a suitable vehicle for chemical analysis of dose preparations.
- Amount of vehicle (if gavage): 5mL/kg body weight - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples of week 4 formulations were analysed to check stability over 4 hours, homogeneity (highest and lowest concentration) and accuracy of preparations (all concentrations).
- Duration of treatment / exposure:
- 28-Days
- Frequency of treatment:
- Once daily
- Remarks:
- Doses / Concentrations:
5, 15, 50 mg/kg/day
Basis:
actual ingested - No. of animals per sex per dose:
- 5 males and 5 females (10 total)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose levels were selected on the basis of a 5-day dose range finding study
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once prior to start of treatment and on days 8, 15, 22 and 28
BODY WEIGHT: Yes
- Time schedule for examinations: Days 1, 8, 15, 22 and 28
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Weekly
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Subjective appraisal was maintained during the study, but no quantitative investigation introduced as no effect was suspected.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Prior to post mortem examination
- Anaesthetic used for blood collection: Yes, light ether anaesthesia
- Animals fasted: Yes
- How many animals: All animals tested
- Parameters checked in table No. 1 (below) were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to post mortem examination
- Animals fasted: Yes
- How many animals: All animals tested
- Parameters checked in table No. 2 (below) were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Week 4 of treatment
- Dose groups that were examined: All animals
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Hearing ability, pupillary reflex, static righting reflex, grip strength, and activity test. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Table No. 3 (below) for parameters examined. All animals surviving to the end of the observation period were anaesthetised using ether vapour and subsequently exsanguinated. All animals assigned to the study were necropsied and descriptions of all macroscopic abnormalities were recorded. Samples were collected and fixed in 4% formaldehyde solution.
HISTOPATHOLOGY: Yes, Table No. 3 (below) for parameter examined. All organs were processed, embedded and cut at a thickness of 2-4 micrometers and stained with haematoxylin and eosin.
Slides of all organs and tissues collected at the scheduled sacrifice from all animals of the control and the highest dose group, and all gross lesions of all animals were examined by a pathologist. Liver, kidneys (males only), spleen and lungs were examined for all rats of the low and mid does groups. - Statistics:
- If the variables could be assumed to follow a normal distribution, the Dunnett-test (many-to-one t-test) based on a pooled variance estimate was applied for the comparison of the treated groups and the control groups for each sex.
The Steel-test (many-to-one rank test) was applied when the data could not be assumed to follow a normal distribution.
All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance.
Test statistics were calculated on the basis of exact values for means and pooled variances. - 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):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- 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:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY: There were no clinical signs of toxicity or behavioural changes over the 28-day observation period that were considered to be related to treatment. No mortality occurred during the study period.
BODY WEIGHT AND WEIGHT GAIN: Body weight gain of low dose males and females during the 4-week treatment period was higher when compared to control animals, and achieved levels of statistical significance on days 8 (both sexes) and day 28 (males only). As a result, body weights of low dose males and females were higher than that of controls after 4 weeks of treatment (for males and not statistically significant for females).
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Slightly lower food consumption was seen in high dose females over the 4 week study period when compared to controls.
An inverse relation to treatment was found for the food consumption in males. Whereas food consumption in males increased at lower dose levels of the test substance. These effects in food consumption correlated with changes in body weights in animals.
HAEMATOLOGY: Treatment related changes were seen in erythrocyte parameters and erythrocyte indices derived thereof and white blood cells in male and female rats.
A dose related increase was seen for the erythrocyte counts (RBC) and decreases in mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH), resulting statistically significant differences in values for RBC in high dose males, for MCV in high dose females and for MCH in high dose males and mid and high dose females. A statistically significant increase in red cell distribution width was seen in both high dose males and high dose females.
An increase number of white blood cells was found in the high dose animals, but achieved a level of statistically significance in females only when compared to controls. Although in both sexes the increase in the number of lymphocytes was mainly responsible for the increase in white blood cells, the increase in number of neutrophils was more pronounced. The increase number of neutrophils in high dose females, both relative and absolute, achieved a level of statistical significance. As a result, the relative number of lymphocytes was statistically significant decreased, despite an increase in absolute number.
In low dose females, statistically significant differences were also found for the increase in relative and absolute number of neutrophils, which was the cause of the statistically significant decrease for relative number of lymphocytes. In the absence of a clear dose related response, the toxicological significance of changes in the differential leucocyte counts in low dose females was doubted.
In the absence of clear changes in the values for haemoglobin and haematocrit, no toxicological significance was attached to the statistically significant changes in mean corpuscular haemoglobin concentration in males of all dose groups and low and mid dose females.
The minor statistically significant decrease in partial thromboplatin time arising between controls and low dose males was considered to have arisen by chance and not to represent a change of biological significance.
CLINICAL CHEMISTRY: In the high dose males and females treated with test substance, increased levels of alanine aminotransferase were reported, reaching levels of statistical significance in the females, when compared to controls for any of the dose levels.
In mid dose males, a statistically significant increase in the level of alkaline phosphatase was seen, whereas a tendency to increased levels was seen in high dose males and females (not statistically significant).
A very slight dose related decrease of total protein, and concurrent decrease of total albumin, was reported, but all values remained well within the historical background data. In high dose females, the values of albumin achieved a level of statistically significance when compared to controls.
The statistical significance for the (increased) levels of sodium in low and mid dose males was considered to have arisen by chance. In the absence of a treatment-related distribution or corroborative findings in the opposite sex, these changes were considered to be of no toxicological significance.
NEUROBEHAVIOUR: No changes were reported in hearing ability, pupillary reflex, static righting reflex and grip strength in the animals treated with test substance, when compared to control animals.
The variation in motor activity between control and treated animals did not indicate a relation with treatment.
ORGAN WEIGHTS: Treatment related changes in liver and spleen weights were found in high dose males and females and in kidneys weights of males of all dose groups.
In males, a statistically significant increase was found for the liver weights and the liver:body weight ratio and in females a level of statistical significance was achieved for the liver:body weight ratio only.
A dose related increase was found for the spleen weights of both males and females. Both absolute and relative spleen weights of high dose animals showed a statistical significance of p<0.01. The relative spleen weights of mid dose females was also statistically significant increase, when compared to controls.
Statistically significant increases were seen for the absolute kidney weights in males of all dose groups. The kidney:body weight ratios were statistically increased in mid and high dose males only.
No toxicological significance was attached to the (statistically significant) difference for heart weights in high dose females, since they were considered to be mainly the result of the changes in (terminal) body weight of the animals compared to that of controls.
GROSS PATHOLOGY: Enlarged size of the spleen was observed in 2/5 males of the high dose group.
The findings of alopecia reported in a few mid and high dose females confirm the clinical signs in these animals and were considered of no toxicological significance.
HISTOPATHOLOGY: NON-NEOPLASTIC: Microscopic findings related to treatment were noted in lungs, liver and spleen as well as in kidneys of male rats only.
Lungs: There was an increase in the incidence and severity of primarily inflammatory alterations in the lungs of mid and high dose rats of both sexes. These consisted of perivascular/peribronchial inflammatory cell foci, alveolar inflammation and foci of alveolar macrophages, which were recorded at minimal to moderate degrees of severity. The level of these findings in the low dose animals were similar to those in the control group.
Liver: In the liver there was an increase in the incidence and severity of multifocal granulomatous inflammation, periportal lymphoid inflammation and single cell necrosis in mid and high dose rats of both sexes. The level of these findings in low dose animals was similar to those in the control group.
Spleen: In the spleen, lymphoid hyperplasia was noted at minimal to moderate degrees of severity in five mid dose and eight high dose rats. This finding was the correlate to the enlarged spleen noted in two high dose males at necropsy.
Kidneys - males: Hyaline droplets in the cortical renal tubules were recorded in all groups of males including controls. However, there was a slight increase in severity - from minimal to slight, and incidence in treated groups. - Dose descriptor:
- NOAEL
- Effect level:
- ca. 5 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: Excluding kidney effects.
- Critical effects observed:
- not specified
- Conclusions:
- Under the current test conditions and excluding the kidney effects NOAEL = 5 mg/kg/day for both male and female rats.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 5 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
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
GLP study conducted according to OECD Guideline 407 and EU Method B. 7. Under the current test conditions and excluding the kidney effects NOAEL = 5 mg/kg/day for both male and female rats.
Justification for classification or non-classification
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.