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EC number: 201-180-5 | CAS number: 79-14-1
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- three-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Study published in 1986
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Three-Generation Reproduction and Dominant Lethal Mutagenesis Studies of Ethylene Glycol in the Rat
- Author:
- L.R. DePass, M.D. Woodside, R.R. Maronpot & C.S. Well
- Year:
- 1 986
- Bibliographic source:
- Fundamental and Applied Toxicology 7, 566-572 (1986)
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The basis for the study design is the “NTP Fertility Assessment by Continuous Breeding Protocol"
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Ethane-1,2-diol
- EC Number:
- 203-473-3
- EC Name:
- Ethane-1,2-diol
- Cas Number:
- 107-21-1
- Molecular formula:
- C2H6O2
- IUPAC Name:
- ethylene glycol
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source: Corporation, Hahnville, Louisiana
- Date of receipt: 22/01/1975
- Description: the sample was 99.93% monoethylene glycol and 0.18% diethylene glycol
- Lot//batch number of test material: Not stated
- Expiration date of the lot/batch: Not stated
- Purity test date: Not stated
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Assumed stable
- Stability under storage conditions:
Assumed stable
- Stability under test conditions:
Assumed stable for the duration of the study
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium:
Not applicable, test item administered as received, no preparation necessary.
- Reactivity of the test substance with the solvent/vehicle/test medium (if applicable): Not applicable, test item administered in diet
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
Administered in diet
TYPE OF BIOCIDE FORMULATION (if applicable):
OTHER SPECIFICS
- measurement of pH, osmolality, and precipitate in the culture medium to which the test chemical is added: None stated
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratory, Wilmington, Mass.
- Age at study initiation: Young adult male and female nulliparous Fischer 344 rats
- Weight at study initiation: Range: Not stated
- Housing: Two per cage in stainless steel wire cage. During mating each male was hosed with two females. After mating and during lactation the female were housed individually in plastic shoebox cage with hardwood chips for nesting.
- Diet (e.g. ad libitum): Purina Formulab 5008 Chow (Ralston Purina Co. St. Louis, Mo)
- Water: ad libitum
- Acclimation period: Not stated
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): Not stated
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle
IN-LIFE DATES: From: Not stated
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): 2 weeks
- Mixing appropriate amounts with (Type of food): with the percentage of test item adjusted, based on the group mean body weight and food consumption, so as to maintain a relatively constant dosage level.
- Storage temperature of food: Not stated
- Details on mating procedure:
- - M/F ratio per cage: 1:2
- Length of cohabitation: Not stated
- Proof of pregnancy: Not stated
- After days of unsuccessful pairing replacement of first male by another male with proven fertility: Not stated
- Further matings after two unsuccessful attempts: Not stated
- After successful mating each pregnant female was caged (how): Not stated
- Any other deviations from standard protocol: Not stated - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Administration of EG to the F0 rats of both sexes began at approximately 7 weeks of age. At approximately 100 days of age, 10 males were mated to 20 females in each dosage group.
The F1 and F2 rats were treated as described for the F0 animals until approximately 100 days of age, at which time the animals were cohabited. Brother and sister mating were avoided for each generation.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Untreated diet control B
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Untreated diet control A
- Dose / conc.:
- 100 mg/kg bw/day
- Dose / conc.:
- 200 mg/kg bw/day
- Dose / conc.:
- 40 mg/kg bw/day
- No. of animals per sex per dose:
- 10 males
20 females - Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: Not stated
- Rationale for animal assignment (if not random): Random assignment
- Fasting period before blood sampling for clinical biochemistry: Not stated
- Other: Administration of EG to the FO rats of both sexes began at approximately 7 weeks of age. At approximately 100 days of age, 10 males were mated to 20 females in each dosage group. The date of parturition and the number of live and dead newborn were recorded for each litter.
The appearance and behaviour of dams and pups were observed daily. Litter size was randomly reduced to 10, if necessary, on Day 4 postpartum. Offspring were
weighed as litters at 4 and 14 days and individually at 21days postpartum, the day they were weaned. F1 rats were randomly selected within each dosage group for the next mating. Each litter was represented
except for those conceived very late in the mating period. The F1 and F2 rats were treated as described for the F0 animals until approximately 100 days of age, at which time the animals were cohabited. Brother and sister matings were avoided for each generation. - Positive control:
- No
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Not stated
- Time schedule: Not stated
- Cage side observations checked in table [No.?] were included. No
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: Not disclosed
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
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not stated
OTHER: Dominant lethal study was also performed, 15 males of F2 per dose from reproductive study were removed from their test item dosing regimen at 155 days of age and bred to three separate sets (one set per week) of 15 untreated females. Each female was killed on Day 12 of gestation, and the ovaries and uteri were examined for the number of live and dead fetuses. In addition, 15 diet control F2 males were given an ip dose of 0.50 g/kg of triethylenemelamine (TEM, Polysciences, Inc., Warrington, Pa.) on the day before mating (positive controls), and mated with three groups of females as previously described. - Oestrous cyclicity (parental animals):
- No detail on oestrous cycle was reported.
- Sperm parameters (parental animals):
- Parameters examined in [all/P/F1/F2] male parental generations: Testis weight & epididymis weight.
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: Yes
- If yes, maximum of [...] pups/litter ([...]/sex/litter as nearly as possible); excess pups were killed and discarded. Yes
PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 ] offspring: Yes
GROSS EXAMINATION OF DEAD PUPS: Yes
ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: No
ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY: No - Postmortem examinations (parental animals):
- SACRIFICE: Yes
- Male animals: All surviving animals
- Maternal animals: All surviving animals
GROSS NECROPSY: Yes
HISTOPATHOLOGY / ORGAN WEIGHTS: Yes - Postmortem examinations (offspring):
- SACRIFICE: Yes
- Male animals: All surviving animals
- Maternal animals: All surviving animals
GROSS NECROPSY: Yes
HISTOPATHOLOGY / ORGAN WEIGHTS: Yes - Statistics:
- Continuous data such as bodyweight weights were compared by analysis of variance validated
by Bartlett’s test for homogeneity of variance. Duncan’s multiple range test was used to identify individual mean differences when indicated by a significant F value. Where Bartlett's indicated heterogenous variances, t tests for equal or unequal variances were used to delineate difference between groups. Pup weight were compared by method of Weil (Weil, 1970). Discontinuous data such as implantation and reproductive indices were compared by multiple sum of ranks test. Frequency data were compared by the x2 test and by Fisher's exact test. Reproductive indices [ fertility index (male & female), days from matting to parturition, gestation index (fraction of pregnancies that resulted in litters with live pups), gestation survival index (fraction of newborn pup alive at birth) 0 -4 day survival index, 4-14 survival index, 4- 21 day survival index] were calculated and evaluated statistically by nonparametric menthols - Reproductive indices:
- Reproductive indices [ fertility index (male & female), days from matting to parturition, gestation index (fraction of pregnancies that resulted in litters with live pups), gestation survival index (fraction of newborn pup alive at birth) 0 -4 day survival index, 4-14 survival index, 4- 21 day survival index]
- Offspring viability indices:
- No particular indices were indicated in the report. However, offspring were examine, weighted as litters at day 4 - 14 and individually at day 21. Survival was also recorded.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- 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:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Endocrine findings:
- not specified
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- The test item did not lead to statistically significant adverse effects on any of the parameters
measured in the three mating intervals. Slight apparent increases in the dominant lethal mutation index, observed during the Week 2
mating for the high-dose (1.0 g/kg/day) group and during the Week 3 mating for the low dose (0.04 g/kg/day) group, were probably random occurrences unrelated to EG treatment. This interpretation is consistent with the absence of a dose-response relationship and the fact that a negative index of similar
magnitude (-8.2%) was observed for the low dose group in the Week 2 mating. When compared to the combined control groups, significant decreases were observed as result of TEM treatment for the number of females with implants, the total number of implants and the number of live implants.
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Details on results (P0)
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- other: Mild focal interstitial nephritist in high dose groups and well as control group. Also unilateral hydronephrosis observed in on F2 male high dose group.
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: P1 (second parental generation)
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P1)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (P1)
- Key result
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Anogenital distance (AGD):
- not examined
- Nipple retention in male pups:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- no effects observed
- Anogenital distance (AGD):
- not examined
- Nipple retention in male pups:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Other effects:
- no effects observed
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Effect levels (F2)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Based on the condition reported in this study, there were no reproductive or dominant lethal effects associated with dietary administration of ethylene glycol with no-observed-adverse-effect-level (NOAEL) considered as 1000 mg/kg/day.
- Executive summary:
To assess the possible effects of ethylene glycol (EG) on reproductive performance and mutagenesis, three-generation reproduction and dominant lethal mutagenesis studies were performed in the Fischer 344 rat. EG was included in the diet at approximate dosages of 1.0, 0.2, and 0.04 g/kg/day during three generations of reproduction, Each generation was bred once. In a dominant lethal mutagenesis study, the F2 males from the reproduction study were bred to three consecutive lots of untreated females at weekly intervals. Concomitantly, another group of untreated F2 males that received a single ip injection of 0.50 mg/kg triethylenemelamine (TEM) were bred similarly to serve as a positive control group.
There was no evidence of increased fetal death was observed in any of the groups receiving. EG produced no effects on fertility, fecundity, or reproductive performance. In addition, there was no evidence of a dominant lethal effect when EG treated males were mated with untreated females.
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