Ethane-1,2-diol

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)

Principles of method if other than guideline:

In a previous study (BASF 80S0385/8243), one male tested with 2 mL/kg bw of the test item showed a testicular atrophy and a diffuse impairment of spermatogenesis. In the group of animals treated with 8 mL/kg bw, the tested concentration was clearly toxic and testicular atrophy with diffuse impairment of spermatogenesis was seen in all treated animals. A further study (BASF 60D0182/8507) was conducted to clarify whether the testicular findings reported above were related to oxalate nephrosis or due to the p-tert.-butyl benzoate present in the test item. For this purpose, one group of animals was treated with 4 mL/kg bw of ethylene glycol with inhibitors (=< 91.8% ethylene glycol, >= 2.8% p-tert.-butyl benzoate) and a further group was treated with ethylene glycol (purity > 99.5%). In this study the 4-week dermal application of both monoethylene glycol and Glysantin G 105 (ethylene glycol with inhibitors) at a dose level of 4.0 mL/kg bw led to erythema on the application area varying in terms of degree and time. However, erythema should be assessed as a questionable test substance effect of subordinate importance since it was only observed on the application area and it was not possible to make a definite differentiation between an effect resulting from the application procedure and a finding relevant for the substance. The slight impairments of spermatogenesis and spermiogenesis observed in individual male dogs of the group treated with 4 mL/kg bw Glysantin G 105 and the sperm content in the epididymis that was reduced compared with the 2 other test groups were however assessed as a definite substance-induced effect. Although these changes were less pronounced than in the group treated with 8 mL/kg bw Glysantin G 105 (BASF 80S0385/8243) and the animals of test group treated with 4 mL/kg bw of ethylene glycol showed no differences from the control group in this study, it was assumed that p-tert.-butyl benzoate contained in Glysantin G 105 might have been responsible of the testicular damage. To verify this assumption, a further study was undertaken, testing Glysantine G 105 (without increased content of p-tert.-butyl benzoate) at dose levels of 2 and 4 mL/kg bw.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethane-1,2-diol

EC Number:

203-473-3

EC Name:

Ethane-1,2-diol

Cas Number:

107-21-1

Molecular formula:

C2H6O2

IUPAC Name:

ethane-1,2-diol

Specific details on test material used for the study:

purity: > 93.4% ethylene glycol and < 1.3% p-tert.butylbenzoic acid

Test animals

Species:

dog

Strain:

Beagle

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: about 14 - 15 months
- Weight at study initiation: 11.3 kg
- Fasting period before study: before blood and urine collection as well as before necropsy, a fasting period of 16 hours was warranted
- Housing: singly in kennels
- Diet: pelleted diet, daily 400 g
- Water: drinking water, ad libitum
- Acclimation period: 7 days

Administration / exposure

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on exposure:

Before application period, the dogs were shaved on the back, flanks, front and waist. The undiluted test substance was applied daily onto the clipped skin. The application area was about 60% of the total body surface. The test substance was not washed off. All animals including those of the control group wore rigid plastic collars to prevent any ingestion of the test substance. Dermal application was carried out up to the day of the specific necropsy of the animals.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

2 other: mL/kg bw

Doses / concentrations 2

Dose / conc.:

4 other: mL/kg bw

No. of animals per sex per dose:

4

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

Check of dead animals twice a day.
Clinical symptoms twice a day.
Daily food consumption and body weight determination.

Sacrifice and pathology:

All animals were assessed by gross pathology, and then a histopathological examination was carried out.

Other examinations:

Two urinalyses were carried out.

Statistics:

yes

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

not examined

Mortality:

no mortality observed

Body weight and weight changes:

not examined

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:

effects observed, treatment-related

Description (incidence and severity):

Incidence of calcium oxalate crystals in the urine of 3 of the 4 male dogs varying in terms of degree and time.

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Several birefringent precipitates in the kidney of one male dog, some of them showing a positive calcium oxalate reaction.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Several birefringent precipitates in the kidney of one male dog, some of them showing a positive calcium oxalate reaction.

Histopathological findings: neoplastic:

not examined

Other effects:

no effects observed

Description (incidence and severity):

2 mL/kg bw:
There were no definite changes that might be causally related to the test substance applied in any of the examinations carried out.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

> 2 200 - < 4 400 mg/kg bw/day

Based on:

test mat.

Sex:

male

Basis for effect level:

histopathology: non-neoplastic

Target system / organ toxicity

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

2 other: mL/kg bw

System:

other: urogenital

Organ:

kidney

Treatment related:

yes

Applicant's summary and conclusion

Conclusions:

No testicular damage that was definitely induced by the test substance was detected in any of the male dogs investigated.
LD50 dermal (dog): > 4000 mg/kg bw