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EC number: 277-288-1 | CAS number: 73138-39-3
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 16 Nov 2000 to 30 Nov 2001
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Remarks:
- No guideline mentioned in study report
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 001
- Report date:
- 2001
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted in 1998
- Deviations:
- yes
- Remarks:
- no immunological effects addressed
- Principles of method if other than guideline:
- No guideline mentioned in study report
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 853947-59-8
- Cas Number:
- 853947-59-8
- IUPAC Name:
- 853947-59-8
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: Harlan ltaly S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Females (if applicable) nulliparous and non-pregnant: not stated
- Age at study initiation: 27-29 days old
- Weight at study initiation: 89.0 - 102.1 g for males and 84.6 - 101.7 g for females
- Fasting period before study: none
- Housing: 5 of one sex to a cage, clear polycarbonate cages measuring 59x38.5x20 cm with a stainless steel mesh lid and floor (Code 1354 G, Techniplast Gazzada S.a.r.1., Buguggiate, Varese). Each cage tray held absorbent paper which was inspected daily and changed three times a week.
- Diet: Altromin MT pelleted diet, A. Rieper, Bolzano, ltaly, ad libitum
- Water: via water bottles, ad libitum
There was no information indicating that any non-nutrient substance likely to influence the effect of the test item was present in the drinking water or in the diet.
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: 16 Nov 2000 to 22 Feb 2001
Administration / exposure
- Route of administration:
- oral: gavage
- Details on route of administration:
- Dose volume of 2 mL/kg body weight
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: The required amount of the test item was dissolved in the vehicle (corn oil). The formulations were prepared daily. The dose was administered to each animal on the basis of the most recently recorded body weight, and the volume administered was recorded for each animal.
VEHICLE
- Justification for use and choice of vehicle (if other than water): not given
- Concentration in vehicle: 125, 250 and 500 mg/mL
- Lot/batch no. (if required): not given
- Purity: not given - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- None
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- once daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: not given
- Positive control:
- None
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: For mortality twice a day
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Pre and post-dose observations of individual animals for signs of reaction to treatment was carried out daily before dosing, approximately 30 minutes and 2 hours after dosing. Once before commencement of treatment and once a week thereafter each animal was subjected to a detailed clinical examination, which included an evaluation of neurotoxicity. Animals were examined in an open arena for a period of three minutes: removal (from cage), handling reactivity, lacrymation, palpebral closure, salivation, piloerection, rearing, motility impairment, arousal (animal activity), vocalisation, stereotypies, unusual respiratory pattern, bizarre behaviour, urination, defecation, clonic and tonic movements, and gait.
BODY WEIGHT: Yes
- Time schedule for examinations: on the day of allocation to treatment groups, on the day that treatment commenced, weekly thereafter and just prior to necropsy.
FOOD CONSUMPTION:
The weight of food consumed by each cage of rats was recorded weekly following allocation and the group mean daily intake per rat was calculated.
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: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: Yes
Both eyes of all animals assigned to the study were examined just prior to the start of treatment, by means of both an ophthalmoscope and a slit-lamp microscope, after the instillation of 0.5% tropicamide (Visumidriatic, Merck, Sharp and Dohme, Rome, ltaly). The eyes of all animals in all groups were re-examined during week
13 of treatment. During the examination particular attention was paid to: anterior chamber, conjunctivae and eyelids, cornea and sclera, iris, lens, posterior segment - vitreous humour, and ocular fundus.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: During week 13 samples of blood were withdrawn under light ether anaesthesia from the retro-orbital sinus of all rats from each group after overnight fasting.
- Anaesthetic used for blood collection: Yes (light ether)
- Animals fasted: Yes
- How many animals: all
- Parameters checked: haematocrit, haemoglobin, red blood cell count, reticulocyte count (not carried out as there were no signs of anaemia), mean red blood cell volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, white blood cell count, differential leucocyte count (neutrophils, lymphocytes, eosinophils, basophils, monocytes, large unstained cells), abnormalities of the blood film, platelets, and prothrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: During week 13 samples of blood were withdrawn under light ether anaesthesia from the retro-orbital sinus of all rats after overnight fasting.
- Animals fasted: Yes
- How many animals: all
- Parameters checked: alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, creatinine, glucose, albumin, total bilirubin, total cholesterol, total protein, sodium, phosphorus, potassium, calcium, and chloride.
URINALYSIS: Yes
- Time schedule for collection of urine: During week 13 samples of overnight urine samples were collected from all rats
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Yes, collection of urine during overnight fasting
- Parameters checked: appearance, volume, specific gravity, pH, protein, total reducing substances, glucose, ketones, bilirubin, urobilinogen, blood, and sediment.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: at the end of the study
- Dose groups that were examined: all
- Battery of functions tested: sensory activity / grip strength / motor activity / other:
The Motor Activity of the first 5 males and 5 females was measured once during week 12 of treatment by an automated activity recording device (Mini Opto-V arimex, Columbus International Corp.). Measurements were performed using a computer generated random order.
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes, broad range of organs
Organ weights: adrenal glands, brain, epididymides, heart, liver, kidneys, ovaries, spleen, testes, thymus, and uterus. - Statistics:
- Standard deviations were calculated as considered appropriate. For continuous variables the significance of the differences amongst groups was assessed by analysis of variance. Differences between each treated group and the control group were assessed by Dunnett's test using a pooled error variance. The homogeneity of the data was verified by Bartlett's test. If data were found to be inhomogeneous a Modified t test (Cochran and Cox) was applied. The mean values, standard deviations and statistical analysis were calculated from the actual values in the computer without rounding off. Microscopic observations were tested for statistical significance using the non-parametric Kolmogorov-Smirnov test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Salivation, mainly slight in severity, was observed in some treated as well as control animals during the study. The incidence of this sign was higher in treated males than in controls while the incidence in treated female groups was almost comparable to control animals. As this sign was noted in both control and treated animals it could be considered to be due to the vehicle used for the administration of the test item.
At the daily pre- and post-dose observations, salivation was occasionally noted just before dosing or 30 minutes after dosing, in a few male and female animals from the low, mid- and high-dose groups. - Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No changes in body weight were observed in males and females from mid- and high-dose groups and females from the low-dose group. However, a reduced body weight increment was observed in low-dose males when compared to controls, mainly from the 3rd to the 6th week of dosing, causing a change in body weight, which achieved statistically significance in most ofthe measurements performed from the 4th week to the end of treatment.
This change, noted in only one sex receiving the low dose-level, was not considered treatment-related.
Terminal body weight was significantly reduced in low-dose males. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Reductions in food consumption of low-dose males were observed on 4 occasions during the study (weeks 2, 3, 5 and 10).
Low-dose females and mid- and high-dose animals did not show any changes in food consumption when compared to controls throughout the study. - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No relevant macroscopic changes were detected in the animals killed at termination which could be considered related to the test item. The macroscopic observations reported did not reveal any significant difference between treatment and control animals killed at termination.
Statistically significant reductions in absolute liver and kidney weights were achieved in low and high-dose males andin relative weights in mid and high-dose males while the absolute liver weight was increased in low-dose females. In addition, absolute spleen weight was increased in mid- and high-dose females and absolute and relative uterus weight was decreased in low-dose females. All these changes were considered to be of no biological relevance as they were not consistent between sexes and not related to any morphological changes at the microscopic examination. - Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The histopathological changes detected did not show any evident differences between the treated and control animals that could be considered treatment-related.
The seminiferous tubules in the testes were evaluated with respect to their stage in the spermatogenic cycle and the integrity of the various cell type present within the different stages. The findings observed were considered to be an expression of spontaneous pathology normally seen in this species. - Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- No abnormalities were detected at the macroscopic observation and histopathological examination of the organs of the reproductive systems such as prostate gland, seminal vesicles, testes and epididymides in males and ovaries and uterus in females. The weights of testes, epididymides, ovaries and uterus were not affected by treatment. In addition, following the evaluation of the seminiferous tubules with respect to their stage in the spermatogenic cycle and the integrity of the various cell type present within the different stages, no abnormalities were noted.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Remarks:
- highest dose tested
- Sex:
- male/female
- Basis for effect level:
- other: absence of adverse toxic effects
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
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.
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