2-ethoxyethanol

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

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

Test material information

Constituent 1

Reference substance name:

2-ethoxyethanol

EC Number:

203-804-1

EC Name:

2-ethoxyethanol

Cas Number:

110-80-5

Molecular formula:

C4H10O2

IUPAC Name:

2-ethoxyethan-1-ol

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 / concentrations

Doses / concentrations 1

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

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 100, 200, 400, 800 µL/kg/day
Basis:
other: test substance, subcutaneously injection rat (4 weeks)

Doses / concentrations 3

Remarks:

Doses / Concentrations:
500, 1000 µL/kg/day
Basis:
other: test substance, oral gavage dog (11 days)

Doses / concentrations 4

Remarks:

Doses / Concentrations:
0, 50, 100, 200 µL/kg/day
Basis:
other: test substance, oral gelatine capsule dog (13 weeks)

Doses / concentrations 5

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)

Key result

Dose descriptor:

NOAEL

Effect level:

93 mg/kg bw/day (actual dose received)

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).

Results: F1 generation

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

93 mg/kg bw/day (actual dose received)

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

Key result

Reproductive effects observed:

yes

Lowest effective dose / conc.:

93 mg/kg bw/day (actual dose received)

Treatment related:

yes

Relation to other toxic effects:

reproductive effects in the absence of other toxic effects

Dose response relationship:

yes

Relevant for humans:

yes

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.