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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed publication

Data source

Reference
Reference Type:
publication
Title:
Teratogenicity and in Vitro Mutagenicity Studies on Nonoxynol-9 and -30
Author:
O. Meyer, P. Haubro Andersen, E. V. Hansen and J. C. Larsen
Year:
1988
Bibliographic source:
Pharmacology & Toxicology 1988, 62, 236-238

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Reproductive parameters were studied during a teratology study of Nonoxynol 9 by the oral route on rats
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Nonoxynol-9/ Antarox CO 630
- Molecular formula (if other than submission substance): (C2-H4-O)mult-C15-H24-O
- Molecular weight (if other than submission substance): 264.406 g/mol
- Substance type: Organic
- Physical state: Dark brown liquid
- Impurities (identity and concentrations): No data available

Test animals

Species:
rat
Strain:
other: Mob: WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Møllegårds Breeding Center Ltd., DK-4623 Skensved, Denmark
- Age at study initiation: (P) 11 weeks
; (F1) No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): Powdered chow (chow 101) ad libitum
- Water (e.g. ad libitum): Acidified water (citric acid, pH 3.5) ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1⁰C
- Humidity (%): 60 ± 5%
- Air changes (per hr): 6-8 air changes/hr
- Photoperiod (hrs dark / hrs light): electric light from 07 p.m. to 07 a.m

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on exposure:
The test substances were dissolved in distilled water and dosed to the mated females by gavage
Details on mating procedure:
- M/F ratio per cage: 1:1
- Length of cohabitation: No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy - Proof of pregnancy: The presence of a plug was checked every evening (designated day 0) and morning (designated day 1).
- After … days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)] No data available
- After successful mating each pregnant female was caged (how): No data available
- Any other deviations from standard protocol: No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6-15 days
Frequency of treatment:
daily
Details on study schedule:
- F1 parental animals not mated until [...] weeks after selected from the F1 litters. No data available
- Selection of parents from F1 generation when pups were [...] days of age. No data available
- Age at mating of the mated animals in the study: 11 weeks

The rats were mated, 1 female per male per cage. The presence of a plug was checked every evening (designated day 0) and morning (designated day 1).
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 250, 500 and 500 mg/Kg bw/day
Basis:
no data
No. of animals per sex per dose:
No. Of pregnant rats: 25, 22, 25, 24 and 21 at 0, 50, 250, 500 and 500 mg/Kg bw/day respectively
Control animals:
yes, concurrent vehicle

Examinations

Postmortem examinations (offspring):
the fetuses were examined for skeletal anomalies

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight: a statistically significant decrease in weight gain Food consumption: No data available
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Body weight: a statistically significant decrease in weight gain Food consumption: No data available
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
effects observed, treatment-related
Description (incidence and severity):
A statistically significant, lower average litter size was observed in 250 mg/Kg bw/day) (P< 0.05) and an increase in pre-implantation loss in groups 250 mg/Kg bw/day and 500 mg/kg/day on days 6-15, P<0.05).

Details on results (P0)

A statistically significant dose-related increase in extra ribs, and rudiments of ribs was observed.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: No clear cut observations leading to any reproductive effects noted

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Details on results (F1)

An increased incidence in foetuses showing slightly dilated pelvic cavity was observed in the group treated with 500 mg/Kg bw/day of NP-9 orally from day 1 to 20 (12/21 litters compared to 5/25 in the controls, P < 0.05).

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No clear cut observations leading to any reproductive effects noted

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No observed Adverse Effect level (NOAEL) for the test compound Nonoxynol-9 is found to be 50 mg/Kg bw/day.
Executive summary:
A teratology study was conducted on rats to evaluate the toxicity potential of Nonoxynol-9. Reproductive parameters were also checked during the study. The test compound was dosed at levels of 0, 50, 250, 500 and 500 mg/Kg bw/day.

 

Pregnant rats given 250 mg or 500 mg NP-9/kg b.wt./day orally exhibited a statistically significant decrease in weight gain. A concominant effect in these dams on reproduction, and an increase in the incidence of extra ribs and dilated pelvic cavity in their foetuses was interpreted as a consequence of a toxic effect of high doses of NP-9.

 

The No observed Adverse Effect level (NOAEL) for the test compound Nonoxynol-9 is found to be 50 mg/Kg bw/day.