2-ethoxyethyl methacrylate

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Remarks:

subchronic toxicity study with additional assessment of reproduction 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:

Zur Toxikologie des Äthylenglykol-Monoäthyläthers], english translation [On the toxicology of Ethyleneglycol-monethylether

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:

subchronic toxicity study with additional assessment of reproduction toxicity

GLP compliance:

no

Limit test:

no

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

Test animals

Species:

other: rat, dogs

Strain:

other: Wistar (rat), Beagle (dog)

Sex:

male/female

Administration / exposure

Route of administration:

other: rats, subcutaneously or oral gavage; dogs, oral gavage, oral gelatine capsule or intravenously

Duration of treatment / exposure:

rat: 13 weeks (7 d/week, oral gavage);
dog: 13 weeks (7 d/week, oral gelatine capsule)

Frequency of treatment:

rats oral gavage: once per day, 7 times per week;
dog oral gelatine capsule: once per day, 7 times per week

Doses / concentrations

Doses / concentrations 1

Remarks:

0, 50, 100, 200, 100/400*, 200/800* µL/kg/day
oral gavage rat (13 weeks); * increased dosing from day 59 (100 to 400, 200 to 800 µL/kg/day

Doses / concentrations 2

Remarks:

0, 100, 200, 400, 800 µL/kg/day
subcutaneous injection rat (4 weeks)

Doses / concentrations 3

Remarks:

0, 50, 100, 200 µL/kg/day
oral gelatine capsule dog (13 weeks)

No. of animals per sex per dose:

5 (rat)
3 (dog)

Control animals:

yes

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOEL

Effect level:

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

Based on:

act. ingr.

Sex:

male

Basis for effect level:

other: testicular changes in male rats and dogs

Results: F1 generation

Effect levels (F1)

Remarks on result:

not measured/tested

Target system / organ toxicity (F1)

Critical effects observed:

not specified

Results: F2 generation

Effect levels (F2)

Remarks on result:

not measured/tested

Target system / organ toxicity (F2)

Critical effects observed:

not specified

Overall reproductive toxicity

Reproductive effects observed:

yes

Lowest effective dose / conc.:

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

Treatment related:

yes

Relation to other toxic effects:

reproductive effects occurring together with other toxic effects, but not as a secondary non-specific consequence 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 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.