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EC number: 500-209-1 | CAS number: 68412-54-4 1 - 2.5 moles ethoxylated
- 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:
- chronic toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, few details but meets basic scientific principles.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- Toxicologic studies of alkylphenol polyoxyethylene surfactants
- Author:
- Smyth HF and Calandra JC
- Year:
- 1 969
- Bibliographic source:
- Toxicol. Appl. Pharmacol. 14:315-334
Materials and methods
- Principles of method if other than guideline:
- A chronic oral repeated dose study was conducted in rats at 0, 40, 200 and 1,000 mg/kg bw/d to evaluate the systemic effects of NPE-4 in rat. Parameters including bodyweight, food consumption, food utilization, mortality, abnormal behavior, clinical chemistry, haematology, gross and histopathological changes were observed at regular intervals.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- NPE-4
- IUPAC Name:
- NPE-4
- Details on test material:
- - Name of test material (as cited in study report): Nonyl 4, also known as NPE-4
- Molecular formula (if other than submission substance): C23H40O5
- Molecular weight (if other than submission substance): 396.5607 g/mol
- Smiles notation (if other than submission substance): O(c1ccc(cc1)CCCCCCCCC)CCOCCOCCOCCO
- InChl (if other than submission substance): InChI=1/C23H40O5/c1-2-3-4-5-6-7-8-9-22-10-12-23(13-11-22)28-21-20-27-19-18-26-17-16-25-15-14-24/h10-13,24H,2-9,14-21H2,1H3
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type: Nonionic surfactant
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Housing: Housed individually in wire-bottom cages
- Diet (e.g. ad libitum): Rockland rat diet
- Water (e.g. ad libitum): Ad libitum
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- not specified
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): The concentration was adjusted from time to time to maintain the dosage constant - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 2 years
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0 mg/kg bw/d (control)
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
40 mg/kg bw/d
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
200 mg/kg bw/d
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
1000 mg/kg bw/d
Basis:
nominal in diet
- No. of animals per sex per dose:
- 35 (plus 5 animals per sex in the highest and control dosage group)
- Control animals:
- yes, plain diet
- Details on study design:
- No data
- Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS/MORTILITY: Yes
- Time schedule: No data
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly for 13 wk and biweekly to 1 year, then monthly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes (for 12 wk and then irregularly thereafter)
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
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
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Before the first dose, and after 3, 6, 12, 18, and 24 months
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: No data
- How many animals: 5 of each sex on the highest dosage and the control diet
- Parameters checked in table [No.?] were examined: Haemoglobin, total red and white blood cell count and differential white cell count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Before the first dose, and after 3, 6, 12, 18, and 24 months
- Animals fasted: No data
- How many animals: 5 of each sex on the highest dosage and the control diet
- Parameters examined: Urinary reducing substances, protein, and formed elements.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER: Animals were observed daily for abnormal behavior - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (including tumors)
After 12 months , 5 of each sex from the highest dosage and from the control groups and 3 of each sex from each of the two lower-dosage groups and after 24 months all were sacrificed
HISTOPATHOLOGY: Yes
- Histopathologic examination of 28 tissues was done on 5 rats of each sex on the highest dosage and in the control diet groups at each sacrifice. - Other examinations:
- Organ weights of kidney, liver and testes were measured
- Statistics:
- Yes, but no details reported
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 specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- 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:
- BODY WEIGHT AND WEIGHT GAIN: At 1000 mg/kg/d both sexes, and at 200 mg/kg/d the females had gained less weight than the controls after 12 months, but did not differ from the controls after 24 months.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): The groups who gained less weight ate less than did the controls, and the growth effect was attributed to poor palatability of the diets.
ORGAN WEIGHTS: A slight elevation of liver weight in relation to body weight in both sexes on an intake of 1000 mg/kg/d was observed
GROSS PATHOLOGY
HISTOPATHOLOGY: Microscopically the livers were normal, hence the slight elevation of liver weight in relation to body weight observed, was not considered to be adverse
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 40 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
None
Applicant's summary and conclusion
- Conclusions:
- The NOAEL of NPE-4 can be considered to be 40 mg/kg bw/d based on no systemic effects observed at any of the tested the dosages in neither sexes.
- Executive summary:
A chronic feeding study was conducted to evaluate the systemic toxicity of NPE-4 in rats. The test material was administered at 0, 40, 200 and 1,000 mg/kg bw/d to rats in the diet over a 2-year period. Each dosage group consisted of 35 male and 35 female rats, with 5 male and 5 female rats in addition in the highest and control dosage groups reserved for periodic clinical test. Food consumption was calculated weekly for 12 weeks, irregularly thereafter. The rats were weighed weekly for 13 weeks, biweekly to 1 year, then monthly. Food utilization was calculated for the first 12 weeks. Animals were observed daily for abnormal behavior. Before the first dose, and after 3, 6, 12, 18 and 24 months clinical tests were performed on the 5 of each sex at the highest dosage and the control diet. All rats dying or sacrificed were carefully examined for gross pathologic changes, including tumors. After 12 months 5 of each sex from the highest dosage and from the control group were sacrificed, 3 of each sex from each of the two lower-dosage groups. After 24 months, all rats were sacrificed and organs were weighed. Histopathologic examination of tissues was conducted on 5 rats of each sex at the highest dosage and in the control group at each sacrifice. All numerical results were evaluated by appropriate statistical tests. At 1,000 (both sexes) and 200 (females) mg/kg/ bw/day, animals gained less weight than the controls after 12 months, but did not differ from the controls after 24 months. The groups that gained less weight ate less than controls and the growth effect was attributed to poor palatability of the diets. A slight elevation of liver weight in relation to body weight in both sexes at 1,000 mg/kg bw/d was observed. Microscopically, the livers were normal, hence the slight elevation of liver weight in relation to body weight was not considered to be adverse. Based on the above results, the NOAEL of NPE-4 can be considered to be 40 mg/kg bw/d based on no systemic effects observed at the lowest dosage in either sex (Smyth HF et al.,1969).
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