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

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1997

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:

1998

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: 36 week feeding study in male rats.
- Short description of test conditions: 40 male Fischer 344 rats were given either a basal diet (control) or the same diet supplemented with 1.5 % CLA for 36 weeks.
- Parameters analysed / observed: food consumption, body weight, cageside observation, histopathological evaluation of 15 organs, haematological analysis

GLP compliance:

not specified

Limit test:

yes

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:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley (Madison, WI, USA)
- Age at study initiation: 5 - 6 weeks
- Housing: individually in stainless-steel cages
- Diet: Purina Rat Chow 5012, ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 5
- Humidity (%): 60 ± 20

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): monthly
- Mixing appropriate amounts with (Type of food): semi-purified AIN-76A diet
- Storage temperature of food: refrigerated

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The CLA was analysed by GC. Ca. 90 % of the linoleic acid was isomerized to CLA.
Three isomers accounted for 85 % of the total isomers: c9, t11, t9. c11, and t10, c12-octadecadienoic acid

Duration of treatment / exposure:

36 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: %

Remarks:

in diet

Doses / concentrations 2

Dose / conc.:

1.5 other: %

Remarks:

in diet

No. of animals per sex per dose:

20 male/dose group

Control animals:

yes, concurrent no treatment

Positive control:

not examined

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily except for weekends

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION:
- Food consumption for each animal determined: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the day of sacrifice
- Anaesthetic used for blood collection: Yes (Ether)
- Animals fasted: Yes
- How many animals: all
- Parameters checked in table 1 were examined.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes (see table 2)

Statistics:

Body weight gain, food consumption, organ weights, relative organ weights, and haematological parameters were compared by Students t-test.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

mortality observed, non-treatment-related

Description (incidence):

One animal in the control group had to be sacrificed pre-scheduled due to signs of distress. A histopathological evaluation revealed a transmural ulcer of the small intestine.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

The mean body weight gain in the control animals was 270.5 ± 31.8 g. The mean body weight gain in the treatment group (258.3 ± 46.5 g) was not significantly different from control.

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:

no effects observed

Description (incidence and severity):

One control rat revealed markedly elevated platelet and granulocyte count. Furthermore, this animal showed depressed values for red blood cells, haematocrit and haemoglobin, indicators of anaemia. However, histopathological evaluation did not confirm this.

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:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Details on results:

The average daily intake of the test substance in the treatment group ranged from 1970 ± mg/kg bw/d in week 1 to 467 ± 52 mg/kg bw/d in week 36.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

> 467 - < 1 970 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Target system / organ toxicity

Key result

Critical effects observed:

no