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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1994

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Effect of Conjugated Linoleic Acid (CLA) on rat development and growth.
- Short description of test conditions: The test item was administered to female animals after mating in concentrations of 0.25 g/100 g diet or 0.5 g/100 g diet in the diet. The pups received the test item via mother milk or via food after weaning.
- Parameters analysed / observed: CLA content in rat milk, CLA tissue concentrations in dams and fetusses, weight (gain),
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
other: Fisher
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Sprague Dawley, Indianapolis, USA
- Age at study initiation:
Experiment I: 8 weeks
Experiment II: 10 weeks
- Housing: individually
- Diet: nonpurified diet (Ralston Purina, St. Louis, MO, USA)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
CLA was mixed in corn oil before addition to the diet.

DIET PREPARATION
- Rate of preparation of diet: weekly
- Mixing appropriate amounts with: basal diet
- Storage temperature of food: +4 °C (under nitrogen to prevent autooxidation)

Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: cohoused
- M/F ratio per cage: 1/1
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy.
Duration of treatment / exposure:
up to 10 weeks
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 other: g/100 g diet
Remarks:
Control diet (CD)
Dose / conc.:
0.25 other: g/100 g diet
Remarks:
control diet with CLA
Dose / conc.:
0.5 other: g/100 g diet
Remarks:
control diet with CLA
Dose / conc.:
0.5 other: g/100 g diet
Remarks:
CD during gestation, CLA during lacation
Control animals:
yes, plain diet

Examinations

Maternal examinations:
BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Time schedule for examinations: weekly

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20, 10 animals of each group
- Organs examined: liver, mammary gland, skeletal muscle and abdominal adipose tissues were then removed. Fetuses were removed, weighed and examined visually for abnormalities.

OTHER:
Collection of individual milk samples at d10 of lactation. Total protein in milk was determined.
Quantification of RNA and DNA from mammary glands was performed.
Statistics:
Data were analysed by ANOVA. Significant differences among means were determined by Tukey's comparisons.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
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:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
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 examined
Pre- and post-implantation loss:
not examined
Total litter losses by resorption:
not examined
Early or late resorptions:
not examined
Dead fetuses:
not examined
Changes in pregnancy duration:
not examined
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined
Changes in number of pregnant:
not examined
Other effects:
not examined

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
> 0.5 other: g/100 g
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects

Maternal abnormalities

Key result
Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): effects observed, treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): Pups which received CLA during gestation and lactation showed a significant increase of body weight compared to control pups.
Reduction in number of live offspring:
not examined
Changes in sex ratio:
not examined
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
not examined
External malformations:
no effects observed
Skeletal malformations:
not examined
Visceral malformations:
not examined
Other effects:
not examined

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
> 0.5 other: g/100 g
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Key result
Developmental effects observed:
no

Applicant's summary and conclusion