reaction mass of (9Z,11E)-octadeca-9,11-dienoic acid and (10E,12Z)-octadeca-10,12-dienoic acid and octadec-9-enoic acid

Developmental toxicity / teratogenicity

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

Test material information

Constituent 1

Reference substance name:

Linoleic acid

EC Number:

200-470-9

EC Name:

Linoleic acid

Cas Number:

60-33-3

Molecular formula:

C18H32O2

IUPAC Name:

octadeca-9,12-dienoic acid

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: Fisher

Details on test animals or test system 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 / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: g/100 g diet

Remarks:

Control diet (CD)

Doses / concentrations 2

Dose / conc.:

0.25 other: g/100 g diet

Remarks:

control diet with CLA

Doses / concentrations 3

Dose / conc.:

0.5 other: g/100 g diet

Remarks:

control diet with CLA

Doses / concentrations 4

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