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EC number: 419-710-0 | CAS number: 42774-15-2 NYLOSTAB S-EED; NYSEED
- 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:
- 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline conform GLP study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Test material form:
- other: solid
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 Germany. Sulzfeld, Germany
- Age at study initiation: 7 weeks
- Weight at study initiation: 230.4 - 260.2 g (males), 138.8 - 201.3 g (females)
- Housing: in groups of two, three or four in Makrolon type-4 cages with wire mesh tops
- Diet (e.g. ad libitum): Pelleted standard Harlan Teklad 2914C (batch no. 39/12) rat/mouse maintenance diet (Provimi Kliba AG, Switzerland), ad libitum
- Water (e.g. ad libitum): community tap water from Itingen, ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 h
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES:
From: 14.11.2012 To: 21.03.2013
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.1% in water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Concentration in vehicle: 4, 15 or 45 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): 120M0216V
- Purity: 0.1% in water
The dose formulations were prepared wekly. Homogenity of the test item was maintained during the daily administration period using a magnetic stirrer. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- On the first treatment day and once during weeks 5 and 12, duplicate samples of the control group as well as three samples (top, middle and bottom) of about 1 g of each concentration were taken prior to dosing for analysis of homogeintiy and concentration. Duplicate samples of about 1 g of each concentration were taken four hours after commencement of dosing to confirm stability.
The analysis was performed by the responsible using a HPLC method. - Duration of treatment / exposure:
- main study:
91/92 days
recovery period:
29 days - Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
50 mg/kg bw/d
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
150 mg/kg bw/d
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
450 mg/kg bw/d
Basis:
actual ingested
- No. of animals per sex per dose:
- main groups: 10
recovery groups: 5 - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on a previous 28 d toxicity study in rats
- Post-exposure recovery period in satellite groups:recovery period 29 days; 5 animals/sex/dose; control and high dose group - Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
twice daily on days 1 to 3; once daliy thereafter
DETAILED CLINICAL OBSERVATIONS: Yes
once weekly during weeks 1 to 3, not performed during recovery
BODY WEIGHT: Yes
once weekly
FOOD CONSUMPTION:
weekly
OPHTHALMOSCOPIC EXAMINATION: Yes
once during the acclimatization period; once during week 13 in animals of the control and the high dose group, as well as in animals of the middle dose group if test item related changes are seen in the high dose, using a direct ophthalmoscope
HAEMATOLOGY: Yes
after week 13 and week 17; blood samples were drawn from the retro-orbital plexus from al animals under light isoflurane anesthesia. The animals were fasted in metabolism cages for approx. 18 h before blood but allowed access to water ad libitum.
The following hematology parameters were determined: erythrocyte count, hemoglobin, hemarocrit, mean corpuscular volume, red cell volume distribution width, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hemoglobin concentration distribution width, reticulcyte count, reticulocyte maturity index (low, medium, high fluorescence), leukocyte count (total), neutrophils, eosinophils, basophils, lymphocytes, monocytes, large unstained cells, platelet count, prothrmbin time, activated partioal thromboplastin time.
CLINICAL CHEMISTRY: Yes
Collection details see above. The following clinical biochemistry parameters were determined: glucose, urea, creatinine, bilirubin (total), cholesterol (total), triglycerides, phospholipids, aspartate amintransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, bile acids, gamma-glutamyl-tersnferase, creatine kinase, sodium, potassium, chloride, calcium, phophorus, protein (total), albumin, globulin, albumin/globulin ratio
URINALYSIS: Yes
after week 13 and 17; urine was collected during 18 h fasting period. The following urine parameters were determined: urine volume, specific gravity, color, appearance, pH value, nitrite, protein, glucose, ketones, urobilinogen, bilirubin, erythrocytes, leukocytes
NEUROBEHAVIOURAL EXAMINATION: Yes
During weeks 13 and 17;
Grip strength: Forelimb and hindlimb grip strength measurements were performed using a push-pull strain gauge. The animals were placed with the forepaws inside a triangular grasping ring and with the hindpaws outside a triangular grasping ring. Using one hand, the animals were held towards the base of the tail and steadily pulled away or towards the ring until the grip was broken. Each measurement was repeated three times.
Locomotor activity: Locomotor activity was measured quantitatvely with AMS Föhr Medical Instruments and DeMe Tec GmbH Activity Monitor System. Animals were monitored during treatment weeks 13 and 17 for a 60minute period and the total activity of this time period was recorded. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
main groups: after 13 weeks
recovery groups: after 17 weeks
HISTOPATHOLOGY: Yes
The following organs/tissues were examined: adrenal glands, aorta, bone marrow (femur), cecum, colon, duodenum, epididymides, esophagus, eyes/optic nerve, heart including auricles, ileum with Peyer's patches, jejunum, kidneys, larynx, lacrimal gland (exorbital), liver, lungs, lymph nodes (mesenteric and mandibular), mammary gland area, ovaries, pancreas, pituitary gland, prostate gland and seminal vesicles incl. coagulating glands, rectum, salivary glands (mandibulr and sublingual), sciatic nerve, skin, spinal cord (cervical, midthoracic and lumbar), spleen, stomach, testes, thymus, thyroid (incl. parathyroid gland), trachea, urinary bladder, uterus incl. oviducts, cervix and vagina, all gross lesions.
Organ weights:
Adrenal glands, brain, epididymides, heart, kidneys, liver, ovaries, spleen, testes, thymus, uterus - Other examinations:
- none
- Statistics:
- The following statistical methods were used to analyze food consumption, body weight, clinical laboratory data, locomotor activity, grip strength, ophthalmoscopic examinations, organ weights and ratios as well as macroscpic findings:
- The Dunnett-test (many to one t-test) based on a pooled variance estimate was applied if variables could be assumed to follow a normal distribution for the comparison of the treated groups and the control groups for each sex.
- The Steel-test (many-one rank test) was applied instead of the Dunnett-test when the data could not be assumed to follow a normal distribution.
- Fisher's exact test
Results and discussion
Results of examinations
- 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:
- 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
- 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:
- no effects observed
- Details on results:
- - Mortality/Viability:
One male treated with 150 mg/kg bw/d was found dead on treatment day 60, but was considered to an incidental death without toxicological relevance. All other animals survived until the scheduled necropsy.
- Clinical signs:
No cllinical signs were noted in males and females treated with 50 mg/kg bw/d of the test item during the course of the study. No test item relatated signs were noted in males and females treated with 150 or 450 mg/kg bw/d of the test item during the treatment and the recovery period.
- Functional observational battery:
No test item related clinical signs were noted in males and females of all treated groups during the treatment and recovery periods.
- Grip strength:
No test item tleated changes of the mean fore- and hindlimb grip strength were noted in males and females when compared with controls during the treatment and recovery periods.
- Locomotor activity:
No test item related differences of mean locomotor activity were noted when comparing controls and test item treated animals in treatment week 13 and in the recovery period.
- Food consumption:
No test item related differences in mean absolute and relative food consumption were noted in test item treated males and females when compared with controls during the treatment and recovery period.
- Body weights:
No test item related changes of the mean body weights and the mean body weight gain of test item treated males and females were noted when compared with controls during the treatment and recovery period.
- Clinical laboratory investigations:
No test item related differences in parameters of hematology, clinical biochemistry and urinalysis were noted in test item treated males and females when compared with control animals at the end of the treatment period and at the end of the treatment free recovery period.
- Organ weights:
No test item related differences in the mean organ weights, mean organ to body weight ratios and mean organ to brain weight ratios were noted in males and females of all test item treated groups when compared with controls at the end of the treatment and at the end of the recovery period.
- Macroscopic/microscopic findings:
No test item related macroscopic findings were noted in males and females. Ther were no treatment-related microscopic findings. All microscopic findings recorded in this study were considered to be within the normal range of background alterations that is seen in untreated animals of this age and strain.
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 450 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: highest dose tested
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Based on the observations made in this 90 d oral toxicity study in rats the NOEL was considered to be 450 mg/kg bw/d (the highest dose tested).
- Executive summary:
Oral administration of the test item to Sprague Dawley rats at doses of 50, 150 and 450 mg/kg bw/ d, for 91/92 days resulted in no deaths of toxicological relevance, no test item-related findings during daily observations or weekly observations (weeks 1 -12), during the functional observation battery (weeks 13 and 17), no differences of toxicological relevance in the fore- and hindlimb grip strength values or locomotor activity, no differences of toxicological relevance in themean food consumption or mean body weight development, no test item-related differences in the ophthalmoscopy, minor test item-unrelated differences in hematology, clinical biochemistry and urinalysis, no toxicologically relevant differences in mean absolute and relative organ weights, and no macroscopical findings of toxicological relevance.
Based on the the results of this study, 450 mg/kg bw/d of the test item was established as NOEL.
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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