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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from a secondary source.

Data source

Reference
Reference Type:
other: Secondary Literature
Title:
Final Report on the Safety Assessment of Triethylene Glycol and PEG-4
Year:
2006
Bibliographic source:
International Journal of Toxicology, 25 (Suppl. 2):121–138, 2006

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
The above experiment was performed to evaluate and assess any toxicological property of the test chemical affecting the reproductive and developmental functions of the test animals
GLP compliance:
not specified
Justification for study design:
No Data Available

Test material

Constituent 1
Chemical structure
Reference substance name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
EC Number:
500-038-2
EC Name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Cas Number:
25322-68-3
Molecular formula:
(C2-H4-O)mult-H2-O
IUPAC Name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Test material form:
not specified
Details on test material:
Details on test material
- Name of test material (as cited in study report): Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated / Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
- Molecular formula (if other than submission substance): (C2-H4-O)mult-H2-O
- Molecular weight (if other than submission substance): 44.0526 g/mol
- Substance type: Organic
- Physical state: No Data Available
- Impurities (identity and concentrations): No Data Available
Specific details on test material used for the study:
Details on test material
- Name of test material (as cited in study report): Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated / Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
- Molecular formula (if other than submission substance): (C2-H4-O)mult-H2-O
- Molecular weight (if other than submission substance): 44.0526 g/mol
- Substance type: Organic
- Physical state: No Data Available
- Impurities (identity and concentrations): No Data Available

Test animals

Species:
rat
Strain:
Fischer 344
Details on species / strain selection:
No Data Available
Sex:
male/female
Details on test animals or test system and environmental conditions:
No Data Available

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
No Data Available
Details on mating procedure:
-Case 1: 1:2; Case 2: 1:10
Beginning 24 h after the last PEG-4 exposure, the males were mated with two naive (nontreated) virgin females. When those females showed evidence of copulation, they were replaced with two more females, until each male had mated with 10 females.

- Length of cohabitation: 10 weeks

Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data Available
Duration of treatment / exposure:
Males were dosed with the test chemical for 5 consecutive days. Female rats were exposed for 10 weeks.
Frequency of treatment:
No Data Available
Details on study schedule:
Deatils on study schedule
- F1 parental animals not mated until [...] weeks after selected from the F1 litters.
- Selection of parents from F1 generation when pups were [...] days of age.
- Age at mating of the mated animals in the study: [...] weeks: No Data Available
Dose Concentration: 0, 5000, 25,000, or 50,000 Ppm
No of animals per sex per dose: 20 animals per dose group.
Details of controls animals: No Data Available
Doses / concentrations
Remarks:
0 ppm (0 mg/kg bw), 5000 ppm (425 ± 45 mg/kg), 25,000 ppm (2441 ± 328 mg/kg), or 50,000 ppm (5699 ± 1341 mg/kg)
No. of animals per sex per dose:
20 animals per sex per dose
Control animals:
yes, concurrent vehicle
Details on study design:
No data Available
Positive control:
A concurrent positive control group of males receiving an i.p. injection of 0.5 mg/kg triethylenemelamine (TEM).

Examinations

Parental animals: Observations and examinations:
No Data Available
Oestrous cyclicity (parental animals):
No Data Available
Sperm parameters (parental animals):
No Data Available
Litter observations:
No Data Available
Postmortem examinations (parental animals):
At the end of the 10th week after the test chemical exposure, males were killed for necropsy. The females were observed and killed on gestation day 15, at which time corpora lutea and implantation sites (resorptions and live embryos) were counted.
Postmortem examinations (offspring):
No Data Available
Statistics:
No Data Available
Reproductive indices:
Implantation Index, Resorption Index, Mating Index.
Offspring viability indices:
No Data Available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
Reproductive parameters, including number of fertile males and number of gravid females with viable implants, were not affected by the test chemical treatment.

Details on results (P0)

Reproductive parameters, including number of fertile males and number of gravid females with viable implants, were not affected by the test chemical treatment. There were no significant preimplantation losses or dominant lethal effects observed.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
< 5 699 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality
gross pathology
histopathology: non-neoplastic
reproductive performance
Remarks on result:
other:
Remarks:
Not Speciifed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: Not Specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Details on results (F1)

No Data Available

Effect levels (F1)

Remarks on result:
not measured/tested

Target system / organ toxicity (F1)

Critical effects observed:
no
System:
other: Not Specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
Based on all the observation, and all the results it was concluded that the NOAEL for the test chemical was found to be 5699 ± 1341 mg/kg.
Executive summary:

This study was performed to evaluate and assess the effects of the test chemical on the reproductive health of the test animals. In this study, the male Fischer 344 rats were exposed to 0, 5000, 25,000, or 50,000 ppm test chemical in drinking water for 5 consecutive days in a dominant lethal assay, wherein 20 rats per group were included for the study. The respective daily consumption levels of the three doses of the test chemical were 425 ± 45, 2441 ± 328, and 5699 ± 1341 mg/kg. At the end of the 5-day dosing period, the test chemical mixed in drinking water was replaced with regular water. Beginning 24 h after the last test chemical exposure, the males were mated with two naive (non treated) virgin females. When those females showed evidence of copulation, they were replaced with two more females, until each male had mated with 10 females or until 10 weeks had passed. At the end of the 10th week after the test chemical exposure, males were killed for necropsy (observations of male toxicity are described in Short-Term Toxicity earlier in this report). The females were observed and killed on gestation day 15, at which time corpora lutea and implantation sites (resorptions and live embryos) were counted. Reproductive parameters, including number of fertile males and number of gravid females with viable implants, were not affected by test chemical treatment. There were no significant preimplantation losses or dominant lethal effects observed. A concurrent positive control group of males receiving an i.p. injection of 0.5 mg/kg of the positive control were bred with naïve females in a similar manner described above. The positive control group showed increased pre- and postimplantation loss, increased early resorptions, and significant dominant lethal effect.