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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 404-170-0 | CAS number: 70750-63-9
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study; well documented study report
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- Stomachs were sampled at termination and preserved due to the changed standard procedures. Determination of accuracy of preparation was carried out in wks 2, 3 & 4 instead of in wk 1 & 4, because analytical method had not been determined in wk 1. These de
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Deviations:
- yes
- Remarks:
- Stomachs were sampled at termination and preserved due to the changed standard procedures. Determination of accuracy of preparation was carried out in wks 2, 3 & 4 instead of in wk 1 & 4, because analytical method had not been determined in wk 1. These de
- Qualifier:
- according to guideline
- Guideline:
- other: US Food and Drug Administration, Bureau of Food, Toxicological Principle for the Safety Assessment of Direct Food Additives And Color Additive Used in Food. (1982).
- Deviations:
- not specified
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Details on test material:
- - Physical state: Blue powder
- Lot/batch No.: Ref Mix 51785
- Purity: 100% - Moisture
-Stable under storage conditions
- Storage condition of test material: At room temperature in the dark
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
-Source: Charles River GmbH Wiga. Sulzfeld, West-Germany
-Age at study initiation: Approximately 6 weeks
-Weight at study initiation: Males: 166~224 g; Females: 139~166 g.
-Fasting period before study: None
-Housing: Animals were housed 5 to a cage (same sex) in stainless steel suspended cages with wire mesh floors.
-Diet (e.g. ad libitum): free access to standard pelleted laboratory animal diet (RMH-B from Hope Farms, The Netherlands)
-Water (e.g. ad libitum): free access to tap-water. Results of chemical and contaminates analyses are archived quarterly.
-Acclimation period: 14 days (7 days pre- and 7 day post randomization) .
ENVIRONMENTAL CONDITIONS
-Temperature (°C): 21± 3 oC
-Humidity (%): 30-70%
-Air changes: 7.5 – 15 air changes per hr
-Photoperiod (12 hrs dark /12 hrs light)
IN-LIFE DATES: From: February 28th, 1989 To: March 28th, 1989
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 1% Aqueous methyl cellulose
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: The test material was prepared at the appropriate concentration as a solution in 1% aqueous methyl cellulose. Analysis of the stability of these formulations showed them to be stable for at least 4 h. Formulations were therefore prepared daily immediately prior to dosing and kept at room temperature.
VEHICLE
- Justification for use and choice of vehicle (if other than water): At all concentration tested, the test substance formed a homogenous suspension in 1% aqueous methyl cellulose, and this preparation was determined to be stable for at least 4 h at room temperature.
- Concentration in vehicle: 10, 40 and 200 mg/g.
- Amount of vehicle (if gavage): 5 ml/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentrations, homogeneity, stability of the test material in 1% aqueous methyl cellulose, and accuracy of preparation of formulation were determined for the subacute 28-day oral toxicity study in the rat using a spectrophotometer method.
Concentration:
Concentration of the test article in vehicle was determined on days 9, 15 and 22. Results of analysis revealed that the concentrations analyzed were in agreement with the concentration prepared.
Homogeneity: the highest and lowest nominal concentrations prepared in week 2 were tested. Samples were taken: one at the top (~90% height), one at the middle (~50% of height), and one at the bottom (~10% of height).
Stability: the highest and lowest nominal concentration prepared in week 2 and 3 were tested immediately after preparation and 4 h after storage at ambient temperature. Samples were taken at 50% height from the glass flask.
Accuracy of preparation: All formulations prepared in week 2,3,4 were analyzed. Samples were taken at 50% height from the glass flask.
Spectrophotometer: Perkin Elmer Lamda 5 (double beam), band pass 1nm, detection wavelength 675 nm, curettes (quarts).
Conclusions: the test substance formed a homogenous suspension in 1% aqueous methyl cellulose, and this preparation was determined to be stable for at least 4 h at ambient temperature. - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- Once daily, approximately the same time each day, 7 days per week.
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0 mg/kg/day active ingredient (vehicle control)
Basis:
other: nominal via gavage
- Remarks:
- Doses / Concentrations:
50 mg/kg/day active ingredient
Basis:
other: nominal via gavage
- Remarks:
- Doses / Concentrations:
200 mg/kg/day active ingredient
Basis:
other: nominal via gavage
- Remarks:
- Doses / Concentrations:
1000 mg/kg/day active ingredient
Basis:
other: nominal via gavage
- No. of animals per sex per dose:
- 5/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose levels based upno a preliminary range finding study. The 10-day range finding study was performed with 3 rats/sex/group at dose levels of 50, 200 and 1000 mg/kg/day to provide a basis for selection of dose levels for the 28-day study. No difference of biological significance were observed in clinical appearance, body weight, food consumption, macroscopic appearance or liver weights between the treated groups of the dose range finding study.
- Rationale for animal assignment (if not random): Random
- Section schedule rationale (if not random): Random - Positive control:
- Not used
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Cage side observations checked in table were included. No.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Day 29
- Dose groups that were examined: vehicle control, 50, 200 and 1000 mg/kg bw/day treated groups.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 29
- Anaesthetic used for blood collection: Yes (pentobarbitone)
-Animals fasted: Yes
- How many animals: 5/sex/dose
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Day 29
- Animals fasted: Yes
- How many animals: 5/sex/dose
- Parameters checked in table 2 were examined.
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data
OTHER: Organ weight, and histopathology - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see table 3) - Statistics:
- The following statistical methods were used to analyze the body weight, food assumption, organ weight, and clinical laboratory data:
Univariate one-way analysis of variance was used to assess the significance of intergroup differences.
In the variable 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 treated groups and the control groups.
The Steel-test (many-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.
Group means were calculated for continuous data and medians were calculated for discrete data (scores) in the summary tables.
Individual values, means, standard deviations and statistics were round off before printing. For example, test statistics were calculated on the basis of extract values for means and pooled variances and then rounded off to two decimal places. Therefore, two groups may display the same printed means for a given parameter, yet display different test statistics values.
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 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):
- not examined
- 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
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Dark feces were noted among all rats receiving the test material. the onset of this clinical finding was recorded as being from day 4 for all treated animals with severity being dose-related.
No other clinical signs of a reaction to treatment were noted.
One male receiving 200 mg/kg/day showed an incidental finding of chromodacryorrhea on day 4 only.
Mortality: One animal (a male receiving 2000 mg/kg) was sacrificed on day 4 due to mis-alignment of its incisors which caused wounding of the gum and an inability to eat.
No mortality occurred as a result of treatment with the test material.
BODY WEIGHT AND WEIGHT GAIN
The body weights and body weight gains of rats receiving the test material were similar to those of controls at all times.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Food intake by treated rats was similar to that of the controls at all times.
FOOD EFFICIENCY
No data.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Not applicable.
OPHTHALMOSCOPIC EXAMINATION:
No data.
HAEMATOLOGY
There were no differences that were considered to have arisen as a result of treatment and any difference that attained a level of statistical significance was considered to have arisen fortuitously.
CLINICAL CHEMISTRY
Male receiving 1000 mg/kg/day had a slight, but statistically significant increased levels of alanine aminotransferase (GPT) when compared to controls.
There were no other differences noted between control and treated rats that were considered to be related treatment with the test material. any other value that achieved level of statistical significance was considered to have arisen fortuitously and not to be of toxicological significance.
URINALYSIS
No data.
NEUROBEHAVIOUR
No data.
ORGAN WEIGHTS
Males received 1000 mg/kg/day has statistically scientifically heavier livers and spleens, after adjustment for body weight, when compared to control values.
No differences were noted between males receiving 50 or 200 mg/kg/day or treated females when compared with controls.
GROSS PATHOLOGY:
Two male receiving 1000 mg/kg/day had dark areas in the stomach that were considered to represent small areas of hemorrhage.
HISTOPATHOLOGY: NON-NEOPLASTIC
Male receiving 1000mg/kg/day showed slight increase in splenic haematopoiesis which was not apparent in males receiving 200 or 50 mg/kg/day, or in treated females.
Small foci of hepatic necrosis were slightly more severe in males receiving 1000 mg/kg/day.
Two males and two females receiving 1000 mg/kg/day had slight hyperkeratosis of the forestomach.
There was no pathological evidence for macroscopically observed area of hemorrhage in the stomach of two males receiving 1000 mg/kg/day.
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
The discoloration of the feces noted clinically was considered consistent with the coloration of the test material. This observation was not therefore considered of biological significance in the toxicological evaluation of the test material.
A primary effect of the test material related to the liver of males receiving 1000 mg/kg/day, and was manifest as increased alanine aminotransferase levels and increased relative liver weights.
Hyperkeratosis, noted in the stomach of both male and female receiving 1000 mg/kg/day, may be indicative of a local, but mild, irritant effect of the test material.
In the absence of any changes in the hematological cell profile, or corroborative effects in females, the toxicological significance of the increased splenic haematopoisis and increased relative spleen weights in males receiving 1000 mg/kg/day must be considered doubtful.
No evidence of a toxic reaction to treatment with the test material was noted at any of the three treatment levels in any of the females or in males receiving 200 or 50 mg/kg/day.
Applicant's summary and conclusion
- Conclusions:
- Oral administration of the test material to rats, by gavage, at dose levels of 1000 mg/kg/day caused (1) increased levels of alanine aminotranserase (male only); (2) increased relative liver and spleen weights (male only); 93) increased splenic hematopoiesis (males only), increased severity of small foci of hepatic necrosis (male only), and slight hyperkeratosis of the forestomach (males and females). From the results, the NOEL of 200 mg/kg/day was established.
- Executive summary:
The 28-day study was carried out to OECD 407 guidelines. The doses used were 1000, 200 & 50 mg/kg/day. No major findings were observed and 200 mg/kg/day was considered to be the NOEL.
At the top dose minor increases in weight were observed in the liver & spleen of males and there were slightly raised alanine aminotransferase levels in 4/5 males.
The increase in splenic haematopoiesis in the top dose males was very slight and in the absence of effect on the blood parameters and findings in females, is considered of no toxicological significance.
Stomach haemorrhage was observed but only in 2/5 males and hyperkeratosis was noted in stomach of males (2/5) & females (2/5) given 1000 mg/kg/day. These stomach effects could have been caused by the mild irritant effect of the substance when given at the top dose.
There was a slight increase in the severity of small foci of hepatic necrosis in top dose males but this was reported as being limited to a few cells and is known to vary wildly, in rats of the age and strain used.
The faeces of all animals were discoloured in a dose response related manner, indicating the excretion of unchanged material.
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)
Čeprav agencija ECHA veliko spletnega gradiva objavlja v vašem jeziku, je ta stran deloma še vedno v angleščini. Več informacij o večjezikovni praksi agencije.
Dobrodošli na spletišču agencije ECHA Vsebina na tej strani ni v celoti podprta z brskalnikom Internet Explorer 7 (in starejšimi različicami). Prosimo, nadgradite vaš brskalnik Internet Explorer na novejšo različico.
Ta stran uporablja piškotke za zagotavljanje najboljše možne uporabniške izkušnje na našem spletišču.
Preberite več o tem, kako uporabljamo piškotke.