N-hydroxysuccinimide

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1971

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1971

Report date:

1971

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

- Principle of test: Test the teratogenic effects of the substance.
- Short description of test conditions: Rats were given the test item for 4 weeks, one week after the beginning of the treatment the breeding started.
- Parameters analysed / observed: Number of births and malformations of the fetuses.

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-hydroxysuccinimide

EC Number:

228-001-3

EC Name:

N-hydroxysuccinimide

Cas Number:

6066-82-6

Molecular formula:

C4H5NO3

IUPAC Name:

1-hydroxypyrrolidine-2,5-dione

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: 3-4 months
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

Administration / exposure

Route of administration:

other: Drinking water (oral) and subcutaneous

Vehicle:

physiological saline

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

Treatment in the drinking water daily. Twice a week injection.

Doses / concentrations

Dose / conc.:

125 mg/kg bw/day (nominal)

Remarks:

On injection days the dose was 225 mg/kg/day (nominal)

No. of animals per sex per dose:

8 female rats

Control animals:

yes, concurrent no treatment

Examinations

Maternal examinations:

Number of births in control and treated groups.

Fetal examinations:

Any visible defects in the fetuses.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not examined

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Maternal developmental toxicity

Number of abortions:

not specified

Pre- and post-implantation loss:

not specified

Total litter losses by resorption:

not specified

Early or late resorptions:

not specified

Dead fetuses:

not specified

Changes in pregnancy duration:

not specified

Changes in number of pregnant:

not specified

Other effects:

not specified

Effect levels (maternal animals)

Key result

Dose descriptor:

NOAEL

Effect level:

> 125 mg/kg bw/day (nominal)

Based on:

test mat.

Results (fetuses)

Fetal body weight changes:

no effects observed

Description (incidence and severity):

No significant differences between number of births in the treated group compared to the control group (control: average 10-12 fetuses/female, treated: average 11 fetuses/female).

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

not specified

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

no effects observed

Description (incidence and severity):

No visible birth defects were observed in the fetuses.

Skeletal malformations:

not examined

Visceral malformations:

not examined

Other effects:

not examined

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

> 125 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reduction in number of live offspring

external malformations

Applicant's summary and conclusion

Conclusions:

The test item seems to have a NOAEL higher than 125 mg/kg bw/day (maximal dose 225 mg/kg on injection days) in rats, based on the number of births and birth defects. However, no conclusion can be drawn due to the insufficient data.

Executive summary:

A study was conducted to assess the teratogenic potential of the test item in rats. Eight Sprague-Dawley rats were treated for four weeks with an aqueous solution of the test item by injection (twice a week) and in drinking water (daily). The injected dose was about 100 mg/kg and the dose in drinking water was about 125 mg/kg, then the days of injection the total dose was 225 mg/kg. The breeding started one week after starting the treatment. No significant differences between the number of births in the treated group compared to the control group (control: average 10-12 fetuses/female, treated: average 11 fetuses/female). No visible birth defects were observed in the fetuses. Under these experimental conditions, the test item seems to have a NOAEL higher than 125 mg/kg bw/day (maximal dose 225 mg/kg on injection days) in rats, based on the number of births and birth defects. However, no conclusion can be drawn due to the insufficient data.