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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: toxicity to reproduction
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no official method, no GLP, decent documentation about methodology, basic/limited info about processing of results data and results; however this publication is key data since the lowest NOEL has been determined here.

Data source

Reference
Reference Type:
publication
Title:
Zur Toxikologie des Äthylenglykol-Monoäthyläthers
Author:
Stenger EG, Aeppli L, Müller D, Peheim E, Thomann P
Year:
1971
Bibliographic source:
Arzneimittel-Forschung (Drug Research) 6, 880-885

Materials and methods

Principles of method if other than guideline:
Method: other: subacute and subchronic toxicity study with respect to reproduction toxicity
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test substance as stated in publication:german language [Äthylenglykol-Monoäthyläther], english name [ethylene glycol monoethyl ether]
Purity: german language [Zur Synthese]
purchased from Merck

Test animals

Species:
other: rats, dogs
Strain:
other: Wistar (rats), Beagle (dogs)
Sex:
male/female

Administration / exposure

Route of administration:
other: rats, subcutaneously or oral gavage; dogs, oral gavage, oral gelatine capsule or intravenously
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
rat: 13 weeks (7 d/week, oral gavage);
rat: 4 weeks (7 d/week, subcutaneousely);
dog: 11 days (oral gavage);
dog: 13 weeks (7 d/week, oral gelatine capsule);
dog: 22 days (intravenously);
Frequency of treatment:
rats oral gavage: once per day, 7 times per week;
rats subcutaneousely: once per day, 7 times per week;
dog oral gavage: once per day, 5 times per week;
dog oral gelatine capsule: once per day, 7 times per week;
dog intravenously: once per day, 5 times per week;
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 50, 100, 200, 100/400*, 200/800* µL/kg/day
Basis:
other: test substance, oral gavage rat (13 weeks); * increased dosing from day 59 (100 to 400, 200 to 800 µL/kg/day
Remarks:
Doses / Concentrations:
0, 100, 200, 400, 800 µL/kg/day
Basis:
other: test substance, subcutaneously injection rat (4 weeks)
Remarks:
Doses / Concentrations:
500, 1000 µL/kg/day
Basis:
other: test substance, oral gavage dog (11 days)
Remarks:
Doses / Concentrations:
0, 50, 100, 200 µL/kg/day
Basis:
other: test substance, oral gelatine capsule dog (13 weeks)
Remarks:
Doses / Concentrations:
0, 100, 500 µL/kg/day
Basis:
other: test substance, intravenously dog (22 days)
No. of animals per sex per dose:
rats: subcutaneously 5, oral gavage 5;
dogs: oral gavage 1, oral gelatine capsule 3, intravenously 2;
Control animals:
yes

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
100 other: µL/kg/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Based on the results of reproductive toxicity (testicular changes in male rats and dogs); value correpsonds to 93 mg/kg bw/day (assuming a density of 0.929 at 20 °C).

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Results subchronic oral gavage rat (13 weeks):

At doses of 50, 100 and 100/400 µL/kg/day (increased dosage from 100 to 400 µL/kg at day 59 of the study period) no treatment related systemic changes in the analysed organs were observed. The administration of 200 µL/kg/day resulted in all 5 male rats in obvious changes in the testes (interstitium loosened oedematously). In the tubuli there was a lack of the last ripening step from the normally arranged germinal epithelium to the spermatocytes. In the spleens of all animals haemosiderin deposits were observed. Nearly same results were observed in the dose group 200/800 µL/kg/day (increased dosage from 200 to 800 µL/kg at day 59 of the study period).

Results subacute subcutaneous injection rat (4 weeks):

The administration of 400 µL/kg/day resulted in all 5 male rats in obvious changes in the testes (interstitium loosened oedematously), lack of further ripening steps of the spermatocytes in the tubuli. These changes were more severe in the 800 µL/kg/day dose group.

Results subchronic oral gavage (gelatine capsules) dog (13 weeks):

At doses of 50 and 100 µL/kg/day no macroscopic nor histological treatment related systemic changes in the analysed organs were observed. At 200 µL/kg/day changes of the testes in the 3 male dogs were seen. In 2 male and one female slight changes were observed at the kidneys.

Applicant's summary and conclusion

Conclusions:
Rats and dogs were administered different concentrations of the test substance 2-ethoxyethanol (orally, subcutaneously, intravenously) in order to evaluate reproductive toxicity. At a dose of 200 µL/kg bw/day serious testes damage was observed in male rats and dogs (interstitium loosened oedematously). Therefore the corresponding NOAEL for reproductive toxicity is 100 µL/kg bw/day, corresponding to 93 mg/kg bw/day.