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EC number: 908-917-6 | CAS number: -
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 18 Jun 1990 - 09 Jan 1992
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Lack of test material details and only 5 days/week dosing protocol.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
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:
- lack of test material details and only 5 days/week dosing protocol, no immunological and reproductive effects addressed
- GLP compliance:
- yes
- Limit test:
- yes
Test material
- Reference substance name:
- Reference substance 001
- Cas Number:
- 151661-88-0
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Sprague-Dawley CD, SPF quality
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: 4 weeks
- Weight at study initiation: 58 - 80 g (males), 62 - 82 g (females)
- Housing: animals were housed in groups of 2-3 in Makrolon 3 cages with softwood bedding (ARWI-Center, Essen, Germany).
- Diet: Haltungsdiät Altromin 1324 DK Chargen-Nr. 2105901304 (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26
- Humidity (%): 40-92
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES:
18 Jun - 23 Okt 1990
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- peanut oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
Dosing solutions were prepared daily by dissolving the test substance in peanut oil yielding a final concentration of 20, 60 and 200 mg/mL.
VEHICLE
- Concentration in vehicle: 20, 60 and 200 mg/mL
- Amount of vehicle (if gavage): 5 mL - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 94/95 days (control and treatment groups)
127 days (recovery groups) - Frequency of treatment:
- once daily, 5 days/week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10 (control)
10 (dose groups)
5 (control and high-dose group as recovery groups) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: According to the author; yielding of a high security range, observation of a not cumulative toxic dose and identification of toxicological relevant ranges as well as the identification of reversibility of a possibly cumulative toxic effect were aimed.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily on weekdays
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD AND WATER CONSUMPTION:
- Food consumption per group in cages: Yes
- Time schedule for examinations: weekly
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: one day before section
- Dose groups that were examined: control and high-dose group
HAEMATOLOGY: Yes
- Time schedule: 6 weeks after application and at study termination
- Blood collection: retroorbital
- Parameters checked: erythrocyte count, hematocrit, mean cell volume, hemoglobin, leucocyte count, thrombocyte count, differential blood count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 6 weeks after application and at the end of the study period
- Parameters checked: gamma glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, sodium, potassium, glucose, urea, protein, calcium, creatinine, cholesterol, chloride, bilirubin - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, whole body, especially eyes, skin, abdomen, chest and skull. Organ weights were examined for brain, testes, heart, liver, spleen, adrenal glands, kidney and thymus.
HISTOPATHOLOGY: Yes, aorta thoracica, eye, colon, proventriculus, small intestine, cerebrum, urinary bladder, skin, heart, testes, hypophysis cerebellum, liver, lung, trachea, axillary lymphnodes, mesentery lymphnodes, spleen, epididymis, adrenal gland, peripheral nerve, kidney, ovary, pancreas, prostate, vesicula seminalis, thyroid gland, salivary gland, esophagus, skeletal muscles, thymus, uterus, tongue, rumen. - Statistics:
- t-test according to Dunnett, C.W. (1955)
Stell-test according to Stell, R.G.D. (1959)
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 300 mg/kg bw/day (one male): a lump of the size of a walnut was observed in Week 11 on the right leg which was of the size of a pinhead at the end of the study, non-adverse.
No compound-related symptoms were observed in the study. One male animal in the 300 mg/kg bw/day dose group had a lump of the size of a walnut in Week 11 on the right leg which was of the size of a pinhead at the end of the study and considered to be non-adverse. - Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred during the study period.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 300 mg/kg bw/day (males): slight increase in mean body weight until Week 2 due to increased body weights at the start of the study, non-adverse.
The total body weight gain of all groups showed no deviation and was comparable to the control group. The slight increase in mean body weight of the low-dose group up to Week 2 was due to increased body weight at the start of the study and therefore considered to be non-adverse. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/day (females): higher food consumption in Week 4, non-adverse.
The mean food consumption in all treated groups was comparable to the control group. The increase in food consumption in the female high-dose group at the beginning of Week 4 up to the end of the study was due to food wasting by the animals. - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- The mean water intake of all groups was comparable to the control group.
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- The examination of the eyes by slit lamp microscope showed no compound-related effects.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 100 and 300 mg/kg bw/day (males): decrease of HCT-value; 1000 mg/kg bw/day (males): decrease of RBC-, HGB-, HCT- value and decrease of lymphocytes ("stabkernige"), increase of monocytes. females: decrease of WBC-values, non-adverse.
The intermediate and the final haematological examinations revealed a decrease of the haematocrit in the male treatment groups. The decrease of the HCT seems to be compound- and partially dose-related (see Table 1 under “Any other information on results incl. tables”). Additionally, the intermediate analysis showed slightly reduced red blood cell count-values for the male high-dose group. The observed deviation of the hematocrit is considered to be incidental, because the diagnosed values are within the +/- 1 SD limits of the historical control. In addition to this, there are no corresponding deviations of the erythrocyte count- or mean cell volume-values to prove the biological relevance of these findings. All other findings were considered to be spontaneous and therefore not related to the treatment. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/day (males): increase in protein-, glucose- and cholesterine- content, increase in calcium and creatinine-content; 100 mg/kg bw/day (males): increase in calcium-content, non-adverse.
The biochemical examinations revealed some compound- and dose-independent findings. In the high-dose group (males) a significant increase in protein-, glucose-, cholesterine- -calcium and creatinine-content was observed. In the low-dose group (males) an increase in calcium-content in comparison to the control value was apparent (see Table 2 under "Any other information on results incl. tables"). - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- The absolute and relative organ weights in all groups showed no deviations and were comparable to the control.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- single spontaneous findings in all groups including coloured thymus, spleen deformation, hydrometra (see Details on results), non-adverse.
The macroscopical examination of the organs displayed some observations like discolouration of the thymus, deformation of the spleen, cyst of the kidney, hydronephrosis, atrophy of the testes, hydrometra and necrosis of the fatty tissue which were considered to be spontaneous. Compound-related macroscopical effects were not observed. The male and female animals of the high-dose recovery group showed no macroscopical compound-related alterations.
Possible target organs have not been diagnosed. In the male and female animals of all groups (including the recovery groups) the livers, the heart and the mandibular lymph node showed effects which were due to a bacterial infection of unknown aetiology. The observed germinal hyperplasia of the mandibulary lymph node can be interpreted as a consequence of this bacterial infection. The liver and the heart of the recovery groups (high-dose group and control group) showed the same signs of bacterial infection and therefore prove the persistence of the bacterial infection. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- single spontaneous findings in all groups including calcification of the arteria pulmonalis, germinal hyperplasia of the mandibulary lymph node, non-adverse.
The microscopical examination revealed no compound-related effects. - Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- The microscopical examination revealed no compound-related effects.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Bacterial infection was observed in all test groups.
Table 1. Results of haematology, gorup mean values.
Dose group [mg/kg bw/day] |
Week |
HCT |
HGB |
RBC |
WBC |
|
males |
control 100 300 1000 |
6 |
43.8 42.2* 41.8** 41.5** |
16.7 16.3 16.3 16.2* |
8.2 8.0 7.9 7.9* |
17.0 18.9 17.2 18.9 |
females |
control 100 300 1000 |
6 |
40.3 39.8 39.9 39.8 |
15.8 15.6 15.7 15.7 |
7.4 7.3 7.3 7.3 |
14.5 15.1 13.6 13.2 |
males |
control 100 300 1000 |
13 |
43.6 41.8** 41.5** 41.2** |
16.7 16.1 16.1 16.1* |
8.7 8.5 8.5 8.4 |
16.4 17.8 17.2 17.2 |
females |
control 100 300 1000 |
13 |
40.0 39.4 39.6 39.6 |
15.9 15.7 15.8 15.9 |
7.5 7.6 7.6 7.5 |
12.1 11.5 10.6 9.0* |
*: Level of significance 95% in comparison with control value.
**: Level of significance 99% in comparison with control value.
HCT: Haematocrit; HGB: haemoglobin; RBC: erythrocyte count; WBC: leucocyte count
Table 2: Results of clinical chemistry, group mean values.
Dose group [mg/kg bw/day] |
Week |
glucose [mmol/L] |
calcium [mmol/L] |
creatinin [µmol/L] |
cholesterine [mmol/L] |
proteine [g/L] |
chloride [mmol/L] |
|
males |
control 100 300 1000 |
6 |
6.4 6.8 6.6 7.0 |
2.5 2.5 2.5 2.6** |
50 51 53 57** |
1.9 2.4 2.2 2.3 |
64 64 64 67** |
103 104 103 103 |
females |
control 100 300 1000 |
6 |
5.5 5.9 5.4 5.7 |
2.6 2.6 2.6 2.6 |
60 59 57 57 |
2.2 2.2 2.2 2.1 |
66 66 67 68 |
102 102 103 102 |
males |
control 100 300 1000 |
13 |
7.4 8.3 7.9 8.7* |
2.5 2.6** 2.6 2.6** |
56 56 58 60 |
1.9 2.4 2.1 2.5* |
66 66 65 68 |
103 103 102 102* |
females |
control 100 300 1000 |
13 |
6.8 7.1 6.5 7.1 |
2.6 2.6 2.6 2.6 |
70 67 67 71 |
2.3 2.2 2.2 2.2 |
69 69 69 71 |
101 102 102 102 |
*: Level of significance 95% in comparison with control value.
**: Level of significance 99% in comparison with control value.
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.
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.
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