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EC number: 203-940-1 | CAS number: 112-15-2
- 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:
- sub-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)
Data source
Reference
- Reference Type:
- publication
- Title:
- Short–term toxicity of diethyleneglycol monoethylether in the rat, mouse and pig .
- Author:
- Gaunt IF, Colley J, Grasso P, Landsdown ABG, Gangolli SD
- Year:
- 1 968
- Bibliographic source:
- Food Cosmet Toxicol 6, 689–705. 1968
Materials and methods
- Principles of method if other than guideline:
- A Repeated Dose Oral Toxicity study was performed for 90 days in pig at doses 167, 500 or 1500 mg/kg/bw/day to evaluate the toxic effects of diethylene glycol monoethyl ether.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2-(2-ethoxyethoxy)ethanol
- EC Number:
- 203-919-7
- EC Name:
- 2-(2-ethoxyethoxy)ethanol
- Cas Number:
- 111-90-0
- Molecular formula:
- C6H14O3
- IUPAC Name:
- 2-(2-ethoxyethoxy)ethanol
- Test material form:
- other: Liquid
- Details on test material:
- - Name of test material (as cited in study report):diethylene glycol monoethyl ether(DGME)
- Molecular formula (if other than submission substance):C6H14O3
- Molecular weight (if other than submission substance):134.174 g/mole
- Substance type:organic
- Physical state:liquid
- Impurities (identity and concentrations):ethanediol: maximal concentration of 0.4%.; arsenic: maximal concentration of 2 ppm; lead: maximal concentration of 10 ppm.
Constituent 1
Test animals
- Species:
- pig
- Strain:
- other: Large White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 6 weeks
- Weight at study initiation: 9.8-10.8 kg (males) and 9.5-10.2 kg (females)
- Housing: Animals were penned individually.
- Diet (e.g. ad libitum): BOCM Hi-lean Rearers Pencils at 0.5-1.5 lb/day
- Water (e.g. ad libitum): Ad libitum
- Acclimatization period: 2 weeks
ENVIRONMENTAL CONDITIONS: Not available
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: The amount of DGME corresponding to each dose level was dissolved in water to give a dose volume of 10 ml/kg. This was added to part of the daily ration given before the main feed.
DIET PREPARATION: Not available
VEHICLE: Water - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0,167, 500, 1500/1000 mg/kg/bw/day, The top dose level was decreased to 1000 mg/kg/day after 3 weeks as severe toxic effects were seen.
Basis:
nominal in diet
- No. of animals per sex per dose:
- Total: 23 pigs
Control:3 males, 3 females
167 mg/kg/day: 3 males, 3 females
500 mg/kg/day: 3 males, 2 females
1500 mg/kg/day: 3 males, 3 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: A previous study in rats had been performed at dietary levels of 0.25, 1.0 and 5 % DGME and adverse effects were observed at the highest dose. The test substance in that study did not meet the required specification, as the sample used contained 0.6% ethylene glycol which was greater than maximum limit of 0.4%. Hence, it was decided that studies using DGME will be carried out with the samples containing less than 0.4% ethylene glycol and including species other than the rat.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available
-OPHTHALMOSCOPIC EXAMINATION: No data available
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At termination of the study.
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: All surviving animals.
- Parameters examined: Haemoglobin concentration, haematocrit values, erythrocyte count, reticulocyte count, and total and differential leucocyte counts.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At termination of the study
- Animals fasted: No data available
- How many animals: All surviving animals.
- Parameters examined: Transaminase and urea levels
URINALYSIS: Yes
- Time schedule for collection of urine: Urine was collected during week 2 and 4 and at week 6 for crystal examination and week 13 for the below mentioned parameters.
- Animals fasted: No data available
- Parameters examined:
Color, pH, microscopic constituents and content of protein, reducing substances, bile salts, blood and glutamic-oxaloacetic transaminase. In addition, as mentioned above, urine samples collected at week 2, 4 and 6 were examined for crystal content.
NEUROBEHAVIOURAL EXAMINATION: No data available - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
At autopsy the brain, heart, liver, kidneys, adrenals, spleen, gonads and thyroid were weighed.
HISTOPATHOLOGY: Yes
Paraffin-wax sections of brain, pituitary, heart, liver, kidneys, adrenals, spleen, gonads, thymus, aorta, lungs, various lymph nodes, stomach, duodenum, ileum, caecum, colon, rectum, sternum, pancreas, skeletal muscle, uterus and urinary bladder were stained with haematoxylin and eosin for histological examination. - Other examinations:
- No other examinations given other than described above
- Statistics:
- No data available
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Mortalities at highest dose of 1500mg/kg bw/day. No deaths on reduction to 1000 mg/kg bw/day.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Mortalities at highest dose of 1500mg/kg bw/day. No deaths on reduction to 1000 mg/kg bw/day.
- 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 specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- MORTALITY: Mortalities observed at the highest dose level when 1500 mg/kg/day dose was administered. One male and one female were killed in extremis on day 14 and a female died on day 21.
Clinical signs prior to death were lethargy at 4-5 days prior to death and laboured respiration and comatose during 24 hours before death.
BODY WEIGHT AND WEIGHT GAIN: No effects observed.
Food consumption: No effects observed.
HAEMATOLOGY:
Lower haemoglobin was observed in males of the 1000 mg/kg bw/day males and severe anaemia associated with reduced erythrocyte count, crenated erythrocytes was evident in animals which died on 1500 mg/kg bw/day dose.
CLINICAL CHEMISTRY: No treatment-related effects were observed.
URINALYSIS: No treatment-related effects were observed.
ORGAN WEIGHTS: Treatment with 1000 mg/kg/day: increased absolute and relative kidney weights.
GROSS PATHOLOGY: No treatment-related effects were observed.
HISTOPATHOLOGY: NON-NEOPLASTIC:
Liver
Centrilobular and midzonal hepatocyte hypertrophy with pyknotic nuclei which was considered to suggest advanced intracellular oedema was observed in both sexes at ≥ 1000 mg/kg/day and in 1/2 females at 500 mg/kg/day. Periportal fatty change was also observed at 1000 mg/kg/day in both sexes and in one female at 500 mg/kg/day.
Kidney
The kidneys showed extensive areas of tubular hydropic degeneration affecting most of the renal cortex in both sexes of the highest dose group and in one female at 500 mg/kg/day.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 167 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed in hematology, clinical chemistry, urinalysis, gross pathology, organ weights or histopathology.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Summary of the lowest treatment levels at which various effects were seen in pigs treated with DGME
Effect |
Pig (mg/kg/day ) |
Growth reduction |
- |
Anaemia |
1000 |
Increased kidney weight |
1000 |
Hydropic degeneration of Kidney |
- |
Liver changes |
500 |
Oxaluria |
500 |
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 167 mg/kg/day when male and female Large White pigs were exposed to diethylene glycol monoethyl ether.
- Executive summary:
In the subchronic study, the toxic effect of diethylene glycol monoethyl ether were evaluated in male and female Large White pigs. The pigs were exposed to the test chemical orally in feed at a concentration of 0, 167, 500, or 1500 mg/kg/day for 90 days. The top dose level was decreased to 1000 mg/kg/day after 3 weeks as severe toxic effects were seen. At 1500 mg/kg/day, severe toxic effects were seen in the form of uraemia, renal and hepatic damage. As a results, the dose was reduced to 1000 mg/kg/day in the remaining survivors (2 males and 1 female) after 21 days. At 1000 mg/kg/day anaemia was seen in males, as well as increased kidney weight and liver changes along with tubular hydropic degeneration were seen in the animals receiving 1000 mg/kg. At 500 mg/kg/day, hydropic degeneration of kidney and liver changes were seen, while no effects were reported in any of the parameters examined at 167 mg/kg/day. Therefore, NOAEL was considered to be 167 mg/kg/day when male and female Large White pigs were orally exposed to diethylene
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