Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
other: Information on metabolite lauric acid.
Adequacy of study:
other information
Study period:
1994
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Does not meet important criteria for today's standard method. Study uses a single dose on day 12 of gestation using a small number of test animals.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1994

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
- Principle of test: An embryotoxicity study of octanoic acid in rats was performed.
- Short description of test conditions:In this study 12 pregnant female rats were dosed with 18.75 mmol/kg of octanoic acid on day 12 of pregnancy. The rats were then sacrificed on day 20 of pregnancy.
- Parameters analysed / observed: The number of fetuses and resorptions counted. The fetuses were also checked for malformations and weight
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: no data
Carbon chain length distrbution: C8
Source: Material was purchased from Sigma Chemical Company, St Louis, MO.
Remarks: Octanoic acid was one of 4 test materials included in the study.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sigma Chemical Company

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: day 6 or 7 of pregnancy
- Housing: small groups in hanging wire cages
- Diet (e.g. ad libitum): Purina Rodent Laboratory Chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 to 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 50 +/- 5
- Photoperiod (hrs dark / hrs light): 12 hrs light/dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on mating procedure:
- Impregnation procedure: purchased timed pregnant
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy
Duration of treatment / exposure:
day 12 of gestation
Frequency of treatment:
single
Duration of test:
eight days (single dose on day 12 of gestation, with sacrifice on day 20)
Doses / concentrations
Dose / conc.:
18.75 other: mmol/kg
No. of animals per sex per dose:
12
Control animals:
other: 10 undosed animals

Examinations

Ovaries and uterine content:
On day 20 of gestation, animals were sacrificed, and the uterine horns were examined for placement of fetuses and counting of resorption sites.
Fetal examinations:
Fetuses were weighted and the sexes were determined. Fetuses were also examined for gross malformations, and fixed in either Bouin's fluid for razor blade sectioning and examination, or alcohol for staining for cartilage and bone examination.
Statistics:
not specified

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Mortality:
mortality observed, non-treatment-related
Description (incidence):
1 of the 12 animals did not survive until the end of the study.

Maternal developmental toxicity

Early or late resorptions:
effects observed, non-treatment-related
Description (incidence and severity):
10 (9%)

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
18.75 other: mmol/kg
Based on:
test mat.
Basis for effect level:
mortality

Results (fetuses)

Fetal body weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
mean fetal weight (M/F): control: 3.9/3.71, test 3.48/3.23
Reduction in number of live offspring:
effects observed, non-treatment-related
External malformations:
effects observed, non-treatment-related
Description (incidence and severity):
# of malformed surviving fetuses: control 1%, test 3%
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
no embryotoxic effects except a slight reduction on fetal body weight

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
18.75 other: mmoles/kg
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Key result
Abnormalities:
not specified

Overall developmental toxicity

Key result
Developmental effects observed:
no

Any other information on results incl. tables

Additional transplacental pharmacokinetic studies indicated that octanoic acid is poorly absorbed via the intestinal tract.

Applicant's summary and conclusion

Conclusions:
The NOAEL (teratogenicity) was 18.75 mmoles/kg.
Executive summary:

An embryotoxicity study of octanoic acid was performed. In this study 12 pregnant female rats were dosed with 18.75 mmol/kg of octanoic acid on day 12 of pregnancy. The rats were then sacrificed on day 20 of pregnancy, and the number of fetuses and resorptions counted. The fetuses were also checked for malformations and weight. Only one of the 12 female rats did not survive until sacrifice. The fetal observations are summarized below:

No. implantation sites: control 108, test 131

No. of resorption or dead fetuses: control 6%, test 9%

No. of malformed surviving fetuses: control 1%, test 3%

Mean fetal weight (M/F): control: 3.9/3.71, test 3.48/3.23

Additional transplacental pharmacokinetic studies indicated that octanoic acid is poorly absorbed via the intestinal tract.