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EC number: 500-425-6 | CAS number: 159034-91-0 1 - 6.5 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
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- Nanomaterial pour density
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- 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
Endpoint summary
Administrative data
Description of key information
The test item was administered daily for 4 weeks by oral route to male and female Sprague-Dawley rats at dose-levels of 100, 300 or 1000 mg/kg/day in corn oil. Under the experimental conditions of this study, the No Observed Adverse Effect Level (NOAEL) was considered to be at 300 mg/kg/day based on the adverse clinical signs observed at 1000 mg/kg/day.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 29 August 2012 - 29 November 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Version / remarks:
- 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: breeder: Charles River Laboratories France, l’Arbresle, France
- Age at study initiation: approximately 6 weeks old
- Mean body weight at study initiation: the males had a mean body weight of 185 g (range: 169 g to 200 g) and the females had a mean body weight of 171 g (range: 148 g to 184 g)
- Fasting period before study: no
- Housing: the animals were housed by five, in polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: a period of 8 days before the beginning of the treatment.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.
IN-LIFE DATES: 07 September 2012 to 05 October 2012. - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test item was administered as a solution in the vehicle. It was mixed with the required quantity of vehicle. The dose formulations were kept under magnetic stirring at least 30 minutes before delivery to the study room.
No correction factor was applied to the calculation of dose-levels.
The frequency of dose formulation preparation was on a daily basis. The dose formulations were delivered to the study room at room temperature and protected from light.
VEHICLE
- Justification for use and choice of vehicle: soluble in the vehicle and corn oil is commonly used for this type of study.
- Concentration in vehicle: 20, 60 and 200 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg/day. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Type of method: GC-FID
Test item concentrations: within the acceptance criteria (± 10%), except for formulations prepared in week 4 for groups 3 and 4 which were respectively at +10.9% and +11.3%. This was considered to have no impact on the study
Homogeneity: not assessed, dose formulation is a solution
Stability: not assessed, dose formulation prepared daily - Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- Daily
- 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 (nominal)
- No. of animals per sex per dose:
- 5 animals per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
The dose-levels were selected in agreement with the Sponsor based on the results of a previous 2 week toxicity study performed in the same species and strain. In this study, three groups of three males and three females received the test item by gavage at 100, 300 or 1000 mg/kg/day as a suspension in corn oil. Another group of three males and three females received the vehicle only. The only test item-related effect seen in this study was ptyalism at 300 and 1000 mg/kg/day.
Therefore, 1000 mg/kg/day was selected as the high dose-level for this 4-week study. Mid and low dose-levels were selected in order to cover approximately 3-fold intervals.
- Rationale for animal assignment: computerized randomization procedure. - Positive control:
- no (not required)
- Observations and examinations performed and frequency:
- MORTALITY/MORBIDITY:
- Time schedule: once a day during the acclimation period and at least twice a day during the treatment period.
- CLINICAL SIGNS:
- Time schedule: once a day, at approximately the same time.
DETAILED CLINICAL OBSERVATIONS:
- Time schedule: once before the beginning of the treatment period and then at least once a week until the end of the study.
BODY WEIGHT:
- Time schedule: once before the beginning of the treatment period, on the first day of treatment and then at least once a week until the end of the study.
FOOD CONSUMPTION:
- Time schedule: once a week until the end of the study.
NEUROBEHAVIOURAL EXAMINATION:
- Time schedule: once in week 4.
HEMATOLOGY, CLINICAL CHEMISTRY, URINALYSIS:
- Time schedule: at the end of the treatment period. - Sacrifice and pathology:
- ORGAN WEIGHTS: at the end of the treatment period.
GROSS PATHOLOGY:
Complete macroscopic post-mortem examination of all study animals.
HISTOPATHOLOGY:
A microscopic examination was performed on:
- all tissues listed in the Tissue Procedure Table for the control and high-dose animals (groups 1 and 4) sacrificed at the end of the treatment period,
- all macroscopic lesions from all low- and intermediate-dose animals (groups 2 and 3) sacrificed on completion of the treatment period. - Other examinations:
- no
- Statistics:
- Citox software (version D.6) was used to perform the statistical analyses of body weight, hematology, blood biochemistry and urinalysis data. PathData software (version 6.2d2) was used to perform the statistical analysis of organ weight data (level of significance: 0.05 or 0.01).
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Ptyalism, breathing difficulties, thin appearance and hunched posture observed at 1000 mg/kg/day and ptyalism noted at 300 mg/kg/day were considered to be test item-related and, with the exception of ptyalism, adverse. The treatment had to be stopped for 1 day for one female following poor health condition.
Ptyalism was observed generally from the first week of the treatment, breathing problems in the second half of the treatment period and hunched posture towards the end of the treatment period. Thin appearance was observed following body weight loss recorded in the affected males.
Incidental findings included scabs, chromodacryorrhea, thinning of hair, eye opacity, lacrimation, half-closed eyes, soiled muzzle, piloerection and bent head. - Mortality:
- no mortality observed
- Description (incidence):
- There were no unscheduled deaths during the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Males treated at 1000 mg/kg/day had a mean terminal body weight and mean body weight gains lower than controls, particularly in the second half of the treatment period. This was considered to be test item-related but non adverse as the mean body weight at the end of the study was affected by -10% only when compared with controls.
There was no dose-relationship in female mean terminal body weight and mean body weight gain over the treatment period; the statistical differences observed were considered to be fortuitous. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Males treated at 1000 mg/kg/day had a mean food consumption toxicologically significantly lower than controls during the last week of treatment (18.7 g/animal/day vs. 23.5 in controls, i.e. -20%). This non adverse effect was considered to be test item-related.
In females, the non dose-related differences from controls in mean food consumption were considered to be fortuitous. - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- There were no test item-related effects. Mean values from test item-treated groups were comparable to those of the controls.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- The statistical differences in blood biochemistry (sodium and chloride) seen in males treated at 100 or 300 mg/kg/day were considered to be fortuitous as no effects at 1000 mg/kg/day thus no dose-relationship and included in historical control data.
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- At 1000 mg/kg/day, there were 3/5 males and 2/5 females with 2 to 4 of the followings findings: hunched posture, dyspnea, piloerection and/or hypoactivity. The males had a trend toward a slight increase of the mean rectal temperature at this dose-level (38.4°C vs. 37.7 in controls). These findings were considered to be test item-related and the clinical signs observed at FOB reminded those observed throughout the study.
At 300 mg/kg/day, one male had dyspnea, piloerection and hypoactivity. As this was observed in one isolated animal, the other animals from this group showing either no findings or only one finding (hunched posture or piloerection), this was considered to be of no toxicological importance at this dose-level.
There were no effects on motor activity considered as test item-related at any dose. - Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No organ weight differences were attributed to Diethylamine modified ethoxylated trimethylolpropane triacrylate.
Statistically higher mean relative-to-body brain and epididymis weights, and lower mean absolute liver weights were observed in males treated at 1000 mg/kg/day. These weight differences were within the range of historical control data and were most likely related to the statistically lower final mean body weights observed in this group.
As other mean weight changes were minimal or of opposing trends between the male and female groups, a relationship to test item treatment was excluded. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No macroscopic findings were attributed to treatment with Diethylamine modified ethoxylated trimethylolpropane triacrylate.
The few gross findings reported were of those commonly observed in the rat of this strain and age and therefore a relationship to test item treatment was excluded. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Moderate (grade 3) multifocal chronic bronchioalveolar inflammation was observed in the lung of one out of five males treated at 1000 mg/kg/day. This was characterized by peribronchial fibrosis foci, minimal hyperplasia of the bronchial epithelium and mixed inflammatory cell infiltrates. Clinical signs were observed in this male: loud breathing on days 20 and 21, along with dyspnea from day 27. Breathing difficulties were also observed in two other males and two females treated at 1000 mg/kg/day and no microscopic findings were noted in the lungs.
This respiratory finding was considered to be possibly test item treatment-related.
Minimal or slight mucification of the vagina epithelium were seen in two out of five females treated at 1000 mg/kg/day (vs. none in controls). As this isolated finding may occur spontaneously in the rat, a relationship to test item treatment was considered to be unlikely.
Other microscopic findings were of those that are commonly observed in the rat of this strain and age and therefore none was considered to be test item treatment-related. - Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical signs
- Critical effects observed:
- no
- Conclusions:
- The test item was administered daily for 4 weeks by oral route to male and female Sprague-Dawley rats at dose-levels of 100, 300 or 1000 mg/kg/day in corn oil. The No Observed Adverse Effect Level (NOAEL) was considered to be at 300 mg/kg/day based on the adverse clinical signs observed at 1000 mg/kg/day.
- Executive summary:
The objective of this study was to evaluate the potential toxicity of the test item following daily oral administration (gavage) to rats for 4 weeks.
The study was performed according to the international guidelines (OECD No. 407 of 03 October 2008 and Commission Regulation No. 440/2008 of 30 May 2008, Part B7) and in compliance with the principles of Good Laboratory Practice.
Methods
Three groups of five male and five female Sprague-Dawley rats received the test item by daily oral administration for 28 days at dose-levels of 100, 300 or 1000 mg/kg/day. The test item was administered as a solution in the vehicle (corn oil) at a constant dosage-volume of 5 mL/kg/day. A control group of five males and five females received the vehicle alone under the same experimental conditions.
Test item concentrations were checked on formulations used in weeks 1 and 4.
The animals were checked at least twice daily during the dosing period for mortality and morbidity and once daily for clinical signs. In addition, detailed clinical examinations were performed at least once weekly. Body weight was recorded once before the beginning of the treatment period, and then at least once a week during the study as food consumption. Towards the end of the dosing period, a Functional Observation Battery (FOB), motor activity measurement, hematology, blood biochemistry and urinalysis were performed on all animals.
On completion of the treatment period, the animals were euthanized and submitted to a full macroscopic post-mortem examination. Designated organs were weighed and selected tissues were preserved. A microscopic examination was performed on selected tissues from control- and high-dose animals sacrificed at the end of the treatment period and on all macroscopic lesions.
Results
The test item concentrations in the administered dose formulations analyzed in weeks 1 and 4 were within the acceptance criteria (± 10%), except for formulations prepared in week 4 for groups 3 and 4 which were respectively at +10.9% and +11.3%. This was considered to have no impact on the study.
At 100 mg/kg/day, there were no toxicologically relevant effects.
There were no unscheduled deaths during the study and no test item-related effects on motor activity at any dose.
The following clinical signs were observed at 1000 mg/kg/day: ptyalism (10/10 animals), breathing difficulties (5/10), thin appearance (2/10) and hunched posture (5/10). Ptyalism was also noted at 300 mg/kg/day in 5/10 animals. Half of the 1000 mg/kg/day animals had hunched posture, dyspnea, piloerection and/or hypoactivity at FOB. The males also showed a trend toward a slight increase of the mean rectal temperature (38.4°C vs. 37.7 in controls). The clinical signs (except ptyalism) observed in the animals treated at 1000 mg/kg/day were considered to be adverse.
At 1000 mg/kg/day, males also had a mean body weight at the end of the study (vs. 359, p<0.05) and mean body weight gains (days 1 to 28: +vs.+170) lower than controls, particularly in the second half of the treatment period, and a mean food consumption toxicologically significantly lower than in controls during the last week of treatment (18.7 g/animal/day vs. controls, i.e. -20%). These findings were considered to be test item-related but not adverse. There were no test item-related effects on mean body weight and mean food consumption in females at 1000 mg/kg/day and in both sexes at 300 mg/kg/day.
At 300 and 1000 mg/kg/day, there were no effects on hematology, blood biochemistry and urinalysis parameters.No mean organ weight differences and no macroscopic post-mortem findings were attributed to the test item at any dose. Moderate (grade 3) multifocal chronic bronchioalveolar inflammation was observed in the lung of one out of five males treated at 1000 mg/kg/day, which could be a major contributing factor to breathing difficulties. This respiratory finding was considered to be possibly test item-related.
Conclusion
The test item was administered daily for 4 weeks by oral route to male and female Sprague-Dawley rats at dose-levels of 100, 300 or 1000 mg/kg/day in corn oil.
Under the experimental conditions of this study, the No Observed Adverse Effect Level (NOAEL) was considered to be at 300 mg/kg/day based on the adverse clinical signs observed at 1000 mg/kg/day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The 28-day repeated toxicity study is considered to be reliable (klimisch score of 1).
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
28 -day repeated toxicity study (Bentz 2013):
The objective of this study was to evaluate the potential toxicity of the test item following daily oral administration (gavage) to rats for 4 weeks (OECD guideline 407). Three groups of five male and five female Sprague-Dawley rats received the test item by daily oral administration for 28 days at dose-levels of 100, 300 or 1000 mg/kg/day. The test item was administered as a solution in the vehicle (corn oil) at a constant dosage-volume of 5 mL/kg/day. A control group of five males and five females received the vehicle alone under the same experimental conditions.
At 100 mg/kg/day, there were no toxicologically relevant effects. There were no unscheduled deaths during the study and no test item-related effects on motor activity at any dose. The following clinical signs were observed at 1000 mg/kg/day: ptyalism (10/10 animals), breathing difficulties (5/10), thin appearance (2/10) and hunched posture (5/10). Ptyalism was also noted at 300 mg/kg/day in 5/10 animals. Half of the 1000 mg/kg/day animals had hunched posture, dyspnea, piloerection and/or hypoactivity at FOB. The males also showed a trend toward a slight increase of the mean rectal temperature (38.4°C vs. 37.7 in controls). The clinical signs (except ptyalism) observed in the animals treated at 1000 mg/kg/day were considered to be adverse.
At 1000 mg/kg/day, males also had a mean body weight at the end of the study (vs.359, p<0.05) and mean body weight gains (days 1 to 28: +vs.+170) lower than controls, particularly in the second half of the treatment period, and a mean food consumption toxicologically significantly lower than in controls during the last week of treatment (18.7 g/animal/dayvs. controls,i.e.-20%). These findings were considered to be test item-related but not adverse. There were no test item-related effects on mean body weight and mean food consumption in females at 1000 mg/kg/day and in both sexes at 300 mg/kg/day.
At 300 and 1000 mg/kg/day, there were no effects on hematology, blood biochemistry and urinalysis parameters.No mean organ weight differences and no macroscopicpost-mortemfindings were attributed to the test item at any dose. Moderate (grade 3) multifocal chronic bronchioalveolar inflammation was observed in the lung of one out of five males treated at 1000 mg/kg/day, which could be a major contributing factor to breathing difficulties. This respiratory finding was considered to be possibly test item-related.
Under the experimental conditions of this study, the No Observed Adverse Effect Level (NOAEL) was considered to be at 300 mg/kg/day based on the adverse clinical signs observed at 1000 mg/kg/day.
Justification for classification or non-classification
Based on the 28 -day study, no severe organ toxicity was showed in rats treated with Diethylamine modified ethoxylated trimethylolpropane tricrylate. No classification is required for the repeated toxicity according to the Regulation EC n°1272/2008.
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