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EC number: 907-131-0 | CAS number: -
- 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:
- two-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- 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:
- Reproductive Toxicity of Triethylene Glycol and Its Diacetate and Dimethyl Ether Derivatives in a Continuous Breeding Protocol in Swiss-CD-1 Mice.
- Author:
- Bossert, N.L., Reel, J.R., Lawton, D., George, J.D., Lamb, J.C.
- Year:
- 1 992
- Bibliographic source:
- Fundamental and Applied Toxicology 18, 602-608
Materials and methods
- Principles of method if other than guideline:
- The study was conducted under the NTP Program's RACB protocol, the details of which have been published previously.
Triethylene glycol and two of its derivatives were evaluated for reproductive toxicity in a continuous breeding protocol with Swiss CD-1 mice. Triethylene glycol (TEG: 0, 0.3, 1.5, and 3%), triethylene glycol diacetate (TGD: 0, 0.75, 1.5, and 3%), and triethylene glycol dimethyl ether (TGDME: 0, 0.25, 0.5, and 1%) were administered in drinking water to breeding pairs (20 pairs per treatment group, 40 control pairs) during a 98-day cohabitation period. Reproductive function was assessed by the number of litters per pair, live pups per litter, proportion of pups born alive, and pup weight. - GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2,2'-(ethylenedioxy)diethanol
- EC Number:
- 203-953-2
- EC Name:
- 2,2'-(ethylenedioxy)diethanol
- Cas Number:
- 112-27-6
- Molecular formula:
- C6H14O4
- IUPAC Name:
- 2,2'-[ethane-1,2-diylbis(oxy)]diethanol
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 6 weeks
- Housing: Throughout these studies, all animals were housed in solid-bottom polypropylene or polycarbonate cages with Ab-Sorb-Dri bedding. Male and female mice were group-housed by sex during quarantine and for the 1-week premating period. Subsequently, the animals were housed individually or as breeding pairs.
- Diet: Ground rodent chow (NIH-07)
- Water: deionized filtered water, ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 0.5 °C
- Photoperiod (hrs dark / hrs light): 14/10
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- The treatment solutions for each test compound were independently formulated by mixing the test compound (w/v) directly into different proportions of distilled water. An aliquot of each formulation of each chemical in the drinking water and the control water and bulk chemical were sent to Midwest Research Institute at 6-week intervals for confirmation of dose levels and certification of the stability of the bulk chemical.
- Details on mating procedure:
- The test substance was administered in drinking water to breeding pairs (20 pairs per treatment group, 40 control pairs) during a 98-day cohabitation period.
- Duration of treatment / exposure:
- beginning 1 week before mating of the F0-generation until end of lactation period of the F2-generation
- Frequency of treatment:
- continuously
- Details on study schedule:
- Reproductive function was assessed by the number of litters per pair, live pups per litter, proportion of pups born alive, and pup weight.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 590 mg/kg bw/day (nominal)
- Remarks:
- 0.3%
- Dose / conc.:
- 3 300 mg/kg bw/day (nominal)
- Remarks:
- 1.5%
- Dose / conc.:
- 6 780 mg/kg bw/day (nominal)
- Remarks:
- 3%
- No. of animals per sex per dose:
- - 20 animals per sex per dose group
- 40 animals per sex in the control group - Control animals:
- yes, concurrent no treatment
- Details on study design:
- This study consists of 4 tasks:
Task 1 - dose-setting study
Task 2 - continuous breeding phase
Task 3 - crossover mating trial used to determine the affected sex when a positive effect on fertility is detected in Task 2
Task 4 - assesses the reproductive performance of the offspring from Task 2 breeding pairs
On the basis of the reduced body weight gain and increased mortality (12.5%) in the 5% test group, exposure levels of 0, 0.3, 1.5 and 3% TEG were selected for this study.
Examinations
- Parental animals: Observations and examinations:
- Body weight, kidney weight, liver weight, mortality, food consumption, water consumption, clinical signs.
- Oestrous cyclicity (parental animals):
- Estrous cycle length
- Sperm parameters (parental animals):
- Sperm concentration, motility, and morphology
- Litter observations:
- Pup growth to weaning, mortality
- Postmortem examinations (parental animals):
- Litters/pair, live pups/litter, cumulative days to litter, absolute testes/epididymis weight, sex accessory gland weight, epidid. sperm parameters.
- Statistics:
- Statistical analysis was performed. The level of significance for all tests was set at p<0.05.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- During Task 2, a total of 6 animals died - 2 females in the control, 1 male and 1 female in the 1.5% test group and 2 females in the 3% test group. The random distribution of deaths across treatment groups suggests that they were not treatment-related.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- TEG during Task 2 had no effect on fertility or reproductive performance as indicated by the proportion of pairs able to produce at least 1 litter, number of litters produced per pair, number of live pups per litter or proportion of pups born alive.
Details on results (P0)
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 6 780 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
Target system / organ toxicity (P0)
- Critical effects observed:
- no
Results: P1 (second parental generation)
General toxicity (P1)
- 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):
- not examined
- Food efficiency:
- not examined
- 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
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P1)
- Dose descriptor:
- NOAEL
- Effect level:
- 6 780 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
Target system / organ toxicity (P1)
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Continuous exposure to 1.5 or 3% significantly reduced mean live pup weight compared to the corresponding weights in the 0 and and 0.3% test group
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- TEG significantly increased liver weight in males and when organ weights were adjusted for body weight, 3% TEG significantly increased female liver weight compared to controls.
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Other effects:
- no effects observed
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Details on results (F1)
Necropsy of the F1 male offspring showed that the highest concentration had no effect on body weight, testis, epididymis, seminal vesicle, or prostate weight, epididymal sperm concentration, percentage motile sperm, or percentage morphologically abnormal sperm. Necropsy of the F1 females showed no change in body or liver weight. The weights of the brain, pituitary, ovary, oviduct, and uterus were similarly unaffected. In contrast, TEG significantly increased liver weight in males and when organ weights were adjusted for body weight, 3% TEG significantly increased female liver weight compared to controls.
Furthermore, similar to the P generation, continuous exposure of the F1 mice to 3% TEG affected neither the mating index nor the fertility index.
Effect levels (F1)
- Generation:
- F1
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (F1)
- 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
- Description (incidence and severity):
- Mice from the final Task 2 litters were weighed at births and on day 21 and day 74 +/- 10, and no significant differences were observed.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Other effects:
- no effects observed
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- no effects observed
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Details on results (F2)
Effect levels (F2)
- Generation:
- F2
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (F2)
- Critical effects observed:
- no
Overall reproductive toxicity
- Reproductive effects observed:
- no
Any other information on results incl. tables
Effect of TEG on fertility and reproductive performance:
0% TEG | 0.3% TEG | 1.5% TEG | 3.0% TEG | |
No. fertile/No. cohabited | 37/37 | 19/20 | 18/18 | 18/18 |
Litters/pair | 4.8 +/- 0.1 (37) | 4.8 +/-0.2 (19) | 4.8 +/- 0.2 (18) | 4.6 +/- 0.3 (18) |
Live pups/litter | 11.7 +/- 0.4 (37) | 12.2 +/- 0.5 (19) | 11.7 +/- 0.6 (18) | 10.9 +/- 0.7 (18) |
Proportions of pups born alive | 0.96 +/- 0.02 (37) | 0.98 +/-0.01 (19) | 0.97 +/- 0.02 (18) | 0.96 +/-0.03 (18) |
Live pup weight (g) | 1.66 +/- 0.02 (37) | 1.63 +/- 0.02 (19) | 1.60 +/- 0.02 (18)* | 1.59 +/- 0.02 (18)* |
* Pairs of mice were cohabited and dosed with the appropoirate chemical for 14 weeks. Pairs were considered fertile if they produced one or more litters.
Effect of TEG on male body and organ weights and sperm parameters at necropsy (The 5th litter produced during Task 2 was allowed to grow until 74 +/- 10 days of age. They received either control or chemical treatment via lactation until weaning and then dosed with drinking water until necropsy at 95 +/- 10 days of age. Each value is the mean +/- SE of 20 mice. ND = parameter not determined.)
Weight or sperm parameter | 0 (control) | 3% |
Body (g) | 33.2 +/- 0.4 | 33.1 +/- 0.9 |
Liver (g) | 2.02 +/- 0.03 | 2.13 +/- 0.05* |
Kidneys/adrenals (g) | ND | ND |
Right testis (mg) | 120 +/- 4 | 115 +/- 4 |
Right epididymis (mg) | 47 +/- 1 | 43 +/- 1 |
Prostate (mg) | 34 +/- 4 | 32 +/- 3 |
Seminal vesicles (mg) | 285 +/- 13 | 305 +/- 17 |
Motile sperm (%) | 52 +/- 7 | 54 +/- 5 |
Abnormal sperm (%) | 5.8 +/- 1.5 | 4.9 +/- 1.4 |
Sperm concentration** | 700 +/- 35 | 719 +/-38 |
* significantly different (p<0.05) from the control group
** No. sperm x 10(3)/mg caudal tissue
Effect of TEG on female body and organ weights at necropsy (The 5th litter produced during Task 2 was allowed to grow until 74 +/- 10 days of age. They received either control or chemical treatment via lactation until weaning and then dosed drinking water until necropsy at 95 +/- 10 days of age. Each value is the mean +/- SE of 20 animals.)
Weight (g) | 0 (control) | 3% |
Body | 30.4 +/- 0.5 | 29.4 +/- 0.6 |
Liver | 2.01 +/- 0.05 | 2.02 +/- 0.07 |
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.