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EC number: 203-951-1 | CAS number: 112-25-4
- 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: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: This study was conducted in accordance with GLP and similar to OECD guideline 410. However, the study duration was only 11 days.
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:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Principles of method if other than guideline:
- Information not available
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2-hexyloxyethanol
- EC Number:
- 203-951-1
- EC Name:
- 2-hexyloxyethanol
- Cas Number:
- 112-25-4
- Molecular formula:
- C6H13OCH2CH2OH
- IUPAC Name:
- 2-hexyloxyethanol
- Details on test material:
- - Name of test material (as cited in study report): Hexyl CELLOSOLVE* (Ethylene glycol monohexyl ether)
- Physical state: liquid
- Analytical purity: 98.16 %
- Stability under test conditions: Stored at room temperature
- Storage condition of test material:
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Inc. Kinston, NY
- Age at study initiation: Approximately 22 week
- Fasting period before study: None
- Housing: Rats were house 1/cage in stainless steel wire floors
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Approximately 2 week
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 61°F and 70°F
- Humidity (%): 40-70 %
- Air changes (per hr): Standard conditions
- Photoperiod: (12 hrs dark / 12 hrs light)
Administration / exposure
- Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- see the attachment-1
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- Nine applications were given over a period of 11 days.
- Frequency of treatment:
- 6/hours/day
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
44 mg/kg/bw/day
Basis:
nominal per unit body weight
- Remarks:
- Doses / Concentrations:
222 mg/kg/bw/day
Basis:
nominal per unit body weight
- Remarks:
- Doses / Concentrations:
444 mg/kg/bw/day
Basis:
nominal per unit body weight
- No. of animals per sex per dose:
- 5/sex/group
- Control animals:
- yes
- Details on study design:
- - Rationale for animal assignment: Random
- Post-exposure recovery period in satellite groups: None - Positive control:
- no data
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule for examinations: Daily
DERMAL IRRITATION (if dermal study): Yes
Time schedule for examinations: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were measured immediately prior to the f i r s t dose (Day 1), one week after the first dose (Day 8), and on the day of sacrifice (Day 12).
FOOD CONSUMPTION: Yes
Food consumption data were collected for a l l animals on days 3, 5, 7, 8, 10, and 12
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to necropsy
- Anaesthetic used for blood collection: Yes (identity) Injections of T 61 euthansia solution
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table [No 13,14.] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: prior to necropsy
- Anaesthetic used for blood collection: Yes (identity) Injections of T 61 euthansia solution
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table [No.15, 16] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: prior to necropsy
- Metabolism cages used for collection of urine: No
- Animals fasted: Yes
- Parameters checked in table [No.17, 18] were examined.
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
At the end of treatment, all rabbits were sacrificed by caudal ear vein injections of T61 Euthanasia Solution. Prior to sacrifice, body weights were obtained to allow expression of relative organ weights. A complete necropsy was performed on each animal. The liver, kidneys, adrenals, brain, and heart of all rabbits and the testes of all males were weighed at the time of
necropsy. - Other examinations:
- Organ weights: The liver, kidneys, adrenals, brain, and heart of all rabbits and the testes of all males were weighed at the time of necropsy.
- Statistics:
- Food consumption, body weight, and organ weight data were intercompared for the dose and control groups by use of Levene's test for homogeneity of variances, by analysis of variance, and by pooled variance t-tests. The t-tests were used, i f the analysis of variance was significant, to delineate which groups differed from the control group. If Levene1s test indicated heterogeneous variances, the groups were compared by an analysis of variance for unequal variances followed,
if necessary, by separate variance t - tests. Non-parametric data were analyzed by the Kruskal-Wallis test or, if necessary, by the Wilcoxon rank sum test as modified by Mann-Whitney,
Frequency data were compared using Fisher's exact tests where appropriate. All statistical tests, except the frequency comparisons were performed using BMDP Statistical Software (Dixon, 1985). The frequency data tests are described in Biometry (Sokal, R. R. and Rohlf, F. J. W. H. Freeman and Company: San Francisco, 1969). The fiducial limit of 0.05 was used as the critical level of significance for all tests.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY: Treatment-related signs of toxicity observed during the study included emaciation, cold extremities, and not eating in three of 5 females from the high dose group. One female in the high dose group died on Day 9 and a second female from this treatment group was sacrificed moribund on Day 10.
Treatment area effects, other than the Draize scored erythema and edema, included dose-related increases in the incidence and/or severity of lichenification , and necrosis, observed in the mid and high dose groups of both sexes. Exfoliation occurred in all male and most female animals at all dosage levels, and fissuring occurred in most animals at the mid and high dose treatment groups for both sexes. Ecchymosis was observed for one male from the mid dose treatment group. Excoriation was noted in two males from the high dose group only, and ulceration was recorded in one male and two females from the high dose group. These lesions principally occurred during the second week of dosing. Erythema in the treatment area scored as barely perceptible (Grade 1) or well defined (Grade 2) was observed after the first day of treatment with test material for most males in the mid and high dose treatment groups (4/5 and 5/5 respectively). Erythema was first observed in the low dose treatment group of males on Day 4. The incidence of males scored with erythema at some time during the study was 4/5, 5/5, and 5/5 for the low, mid, and high dose groups, respectively with the highest incidence and severity recorded on Days 7 and 8. Edema in male rabbits treated with Hexyl CELLOSOLVE was more prominent than erythema in the male animals from the mid and high dose treatment groups. Well defined (Grade 2) to moderate (Grade 3) edema was recorded for all males in the high dose group by Day 5 with barely perceptible edema scored for two animals on Day 3. Edema was observed in 1/5 males in the mid dose group on Day 3 and all animals by Day 4. The majority of the scores for these animals were well defined (Grade 2) or moderate (Grade 3) throughout the remainder of the study. Edema, like erythema, tended to be scored higher in the middle of the study (Days 7 and 8). No edema was observed in males from the low dose group at any time during the study.
BODY WEIGHT AND WEIGHT GAIN: Weight loss (a mean of -182 g) was observed for males in the high dose group during the first week of the study compared to a weight gain of 35 g for controls. Although a slight weight gain was observed for the males in the high dose group between Days 8 and 12, the mean weight for this group was 154 g lower than the initial weight on Day 12. No treatment-related effects body weight or body weight gain was noted in males from either the low or mid dose treatment groups. Females from the high dose group also lost weight during the first week of the study with a moderate recovery observed between Days 8 and 12. The mean body weight was less than the Day 1 weights for the females from the high dose group by 523 and 403 grams, respectively on Days 8 and 12 of the study compared to gains of 27.8 and 51.5 grams observed for controls at these time intervals. No treatment-related effects were noted in females from either the low or mid dose treatment group.
FOOD CONSUMPTION: A trend toward reduced food consumption was observed for males during the first week of the study with reductions of 2.5%, 6.5% and 35.62 for the low, mid, and high dose treatment groups, respectively when compared to control values. Only the reduction in the high dose group was statistically significant. During the second week of the study, only the high dose group showed reduction in food consumption (17.62). This difference was not statistically significant. Females in the mid and high dose treatment groups showed reductions in food consumption of 7.9% and 69.7% for the first week of the study, with a 6.6% and 44.3% reduction for the second week of the study when compared to control values. The high level reduction for the first week of the study was the only value that was statistically significant.
HAEMATOLOGY: Male and female rabbits receiving 444 mg/kg/day of Hexyl CELLOSOLVE had
Statistically significant decreased erythrocyte counts (23.8% and 21.7% decreases from control, respectively), hemoglobin concentration (17.9% and IA.3% decreases, respectively), and hematocrit (.6.3% and 12.7% decreases, respectively). MCV values were increased by 11.2% for both male and female high dose animals, although only the increase in the value for males was
Statistically significant. Female rabbits in the 222 mg/kg/day group had a decreased hematocrit value (7.1% decrease) which was statistically significant. A trend for these alterations was observed in all exposure groups in males, and at least the two highest dose groups for females.
CLINICAL CHEMISTRY: There were no other treatment-related changes in serum clinical chemistry measurements for either males or females in any dose group
URINALYSIS: There were no other treatment-related changes in serum urinalysis measurements for either males or females in any dose group.
ORGAN WEIGHTS: No treatment-related differences in absolute or relative organ weights were observed for males or females from any treatment group. Males from the high dose group had elevated brain weights relative to body weight which resulted from the lower body weights for this group.
GROSS AND HISTOPATHOLOGY: Treatment-related gross and microscopic findings in rabbits surviving to the end of the study were limited to the treated skin. Microscopically, the treated skins of the majority of the rabbits in all of the Hexyl CELLOSOLVE treated groups were characterized by ancanthosis, hyperkeratosis and dermatitis. The dermatitis was ulcerative in nature in the most severely affected rabbits (primarily individual rabbits in the mid and high dose groups), and epidermal/dermal necrosis was present in the treated skins of a small number of rabbits in the high dose group. The histologic changes present in the treated skins were similar for the male and female rabbits on study. In the 2 females from the high dose group that died, gross and microscopic findings in the treatment area were similar to those in the animals that were sacrificed. No cause of death was obvious from these evaluations.
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 44 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: local skin irritation
- Dose descriptor:
- NOAEL
- Effect level:
- 222 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: systemic effects
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
None
Applicant's summary and conclusion
- Conclusions:
- Based on the results of this study the LOAEL for local effects is 44 mg/kg bw/day and the NOAEL for systemic effects is 222 mg/kg bw/day.
- Executive summary:
New Zealand White rabbits (5/sex/group) were exposed to undiluted ethylene glycol hexyl ether by occluded cutaneous contact at doses of 0, 44, 222, or 444 mg/kg body weight/day (0, 0.05, 0.25, or 0.5 ml/kg/day). Nine applications (6 hours/day) were given over an 11-day period. A control group had water applied to the treatment site at a dose of 0.5 ml/kg/day.
Monitors effects included clinical observations, body weights, food consumption, hematology, clinical chemistry, urinalysis, organ weights, gross and histopathology.
Survivors were sacrificed the day following the final application of test material or water. One female in the high dose group died on Day 9 and a second female from this treatment group was sacrificed moribund on Day 10. The cause of death could not be determined from the evaluations performed in this study. No overt indications of treatment-related toxicity were observed, however, and death may have resulted from stress due to the skin irritation and dosing procedures used. Barely perceptible erythema was observed in male rabbits in the 44 mg/kg/day dose group. Barely perceptible to well-defined erythema was observed in males from the mid and high dose treatment levels. Graded erythema showed a dose-response relationship ranging from barely perceptible in the low dose group to moderate in the high dose group for female rabbits. Edema, scored as barely perceptible to moderate, was recorded for male rabbits in the mid and high dose levels. Graded edema showed a dose-response relationship ranging from barely perceptible in the low dose group to severe in the high dose group for females. Some individual variation in response to the irritant properties of the test material was observed. There was a tendency for the erythema and edema observed in this study to be of higher incidence and severity in the middle dosing days (particularly Days 7 and 8). Since no applications were given on Days 6 and 7, the cause of this effect is unclear.
The results of this study indicated that repeated percutaneous exposure of ethylene glycol hexyl ether to rabbits resulted in dose related local skin irritation at doses of 44 mg/kg/day and above.
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