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Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed publication

Data source

Reference
Reference Type:
publication
Title:
Cycloalkanones. 7.' Hypocholesterolemic Activity of Aliphatic Compounds Related to 2,8-Dibenzylcyclooctanone
Author:
G. L. Carlson, I. H. Hall, and C. Piantadosi
Year:
1975
Bibliographic source:
Journal of Medicinal Chemistry, 1975, Vol. 18, No. 10 pp 1024-1026

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: No data
Principles of method if other than guideline:
To evaluate the Antifertility Activities of test chemical in female CF1 mice.
GLP compliance:
not specified
Type of method:
in vivo

Test material

Constituent 1
Reference substance name:
111-13-6
IUPAC Name:
111-13-6
Constituent 2
Chemical structure
Reference substance name:
Octan-2-one
EC Number:
203-837-1
EC Name:
Octan-2-one
Cas Number:
111-13-7
Molecular formula:
C8H16O
IUPAC Name:
octan-2-one
Test material form:
liquid
Details on test material:

- Name of test material: Octan-2-one
- Molecular formula: C8H16O
- Molecular weight: 128.21 g/mol
- Substance type: Organic
- Physical state: Liquid
Specific details on test material used for the study:
- Name of test material: 2-octanone
- IUPAC name: octan-2-one
- Molecular formula: C8H16O
- Molecular weight: 128.2134 g/mol
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): No data available

Test animals

Species:
mouse
Strain:
CD-1
Sex:
female
Details on test animals or test system and environmental conditions:
- Source: Carworth Farms
- Diet (e.g. ad libitum):Purina lab chow, ad libitum
- Water (e.g. ad libitum):water ad libitium

Administration / exposure

Route of administration:
intraperitoneal
Type of inhalation exposure (if applicable):
not specified
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1 %
Details on exposure:
DOSAGE PREPARATION (if unusual): Test compound was suspended in 1% carboxymethylcellulose- H20 (1% CMC) and homogenized

VEHICLE
- Concentration in vehicle:50 mg/kg
- Amount of vehicle (if gavage): No data
- Justification for choice of vehicle: 1% carboxymethylcellulose- H20 (1% CMC)
- Lot/batch no. (if required):
- Purity:
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
approx 19.4(gestation days) days.
Frequency of treatment:
Daily
Duration of test:
approx 19.4(gestation days) days.
Doses / concentrations
Dose / conc.:
50 mg/kg bw/day
No. of animals per sex per dose:
Total no of animals-78 females
0 mg/kg/day-62 female rats
50 mg/kg/day-8 female rats
Diethyl stilbestrol: -8 female rats
Control animals:
yes, concurrent vehicle
Details on study design:
Diethyl stilbestrol was used as positive control.
Statistics:
Yes, Student's t test and standard deviation were measured

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
clinical signs
other: No effect on Number of reabsorption sites and dead in utero per litter, viable foetuses per litter

Observed effects

No toxic clinical sign and change in body weight were observed in treated female mice at 50 mg/kg as compared to control. In addition, no reproductive effect such as number of reabsorption sites, dead in utero per litter, percent pregnant and number of viable foetuses per litter as compare to control.

Any other information on results incl. tables

Antifertility Activities of Aliphatic Analogs of test chemical in CF1 Mice

 

Sr no

Compound

N

%pregnant

% average no. of foetuses per littera

% average no. of reabsorption sites per littera

1

Control

62

100

100±25

100±25

2

test chemical

8

75

87

0

3

Diethyl stilbestrol 

8

0

0

0

aAverage number of foetuses for CF1 mice = 12 ±3 and average number of reabsorption = 0.48 ± 0.12 per litter.

These values are considered to be 100%.

 

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 50 mg/kg bw /day for P and F1 generation when CF-1 female mice were treated with test chemical daily approx 19.4(gestation days) days.
Executive summary:

In an antifertility activity study, CF-1 female mice were treated with test chemical in the concentration of 50 mg/kg in 1% carboxymethylcellulose- H20 (1% CMC) and homogenized and administrated daily by intraperitoneally. No toxic clinical sign and change in body weight were observed in treated female mice at 50 mg/kg as compared to control. In addition, no reproductive effect such as number of reabsorption sites, dead in utero per litter, percent pregnant and number of viable foetuses per litter as compare to control. Therefore, NOAEL was considered to be 50 mg/kg bw /day for P and F1 generation when CF-1 female mice were treated with test chemical daily.