Fatty acids, C8-10

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 Mar - 16 June 1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1969

Report date:

1969

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Rats were fed a diet containing 5, 10 and 25% oleic acid over a time period of 84 days.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Oleic acid

EC Number:

204-007-1

EC Name:

Oleic acid

Cas Number:

112-80-1

Molecular formula:

C18H34O2

IUPAC Name:

octadec-9-enoic acid

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Weight at study initiation: 115-116 g
- Housing: individually in wire bottomed steel cages, animals were also ear punched
- Diet (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): standard rat ration

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

84 days

Frequency of treatment:

no data

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

5 other: %

Remarks:

equivalent to ca. 2500 mg/kg bw/day
(calculated based on the average daily food consumption of 5 g/100 g bw (WHO, 1987))

Doses / concentrations 2

Dose / conc.:

10 other: %

Remarks:

equivalent to ca. 5000 mg/kg bw/day
(calculated based on the average daily food consumption of 5 g/100 g bw (WHO, 1987))

Doses / concentrations 3

Dose / conc.:

25 other: %

Remarks:

equivalent to ca. 12500 mg/kg bw/day
(calculated based on the average daily food consumption of 5 g/100 g bw (WHO, 1987))

No. of animals per sex per dose:

10

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations: abnormal reactions and mortality


BODY WEIGHT: Yes
- Time schedule for examinations: weekly for five rats of each sex of each group


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined: collected weekly for five rats of each sex in all groups

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at day 84 of feeding
- How many animals: five rats of each sex in the control and 25% dosage group and three rats of each sex in the 10% group
- Parameters checked: hematocrit, hemaglobin concentration, erythrocyte count, total and differential leukocyte count, reticulocyte count, prothrombin time and cell index (MCV, MCH, MCHC)


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at day 84 of feeding
- How many animals: five rats of each sex in the control and 25% dosage group and three rats of each sex in the 10% group
- Parameters checked: fasted serum glucose, total cholesterol, blood urea nitrogen, total protein, serum alkaline phosphatase (SAP), serum glutamic-pyruvic transaminase (SGPT), serum glutamic-oxalacetic tranaminase (SGOT), A/G ratio and Icterus index


URINALYSIS: Yes
- Time schedule for collection of urine: at day 84 of feeding
- Parameters checked: protein, glucose, pH, specific gravity and microscopic elements


NEUROBEHAVIOURAL EXAMINATION: Yes

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, all animals that died during the study were examined grossly unless examination was precluded by post-mortem autolysis. At the end of the 90-day feeding period, all surviving rats were necropsied, and organ weights were recorded for liver, kidneys, spleen, gonads, adrenals, heart, thymus and brain.

HISTOPATHOLOGY: Yes, histopathological examinations were conducted on: brain, spinal cord, pituitary, thyroid, parathyroid, thymus, salivary glands, stomach, small and large intestines, liver, pancreas, kidneys, adrenals, spleen, heart, trachea, lungs, aorta, testes, seminal vesicle, ovary, uterus, prostate, urinary bladder, lymph nodes, peripheral nerve, bone marrow, skeletal muscle, bone (femur), eye and optic nerve.

Statistics:

Organ and body weights were analyzed using analysis of variance and a t-test.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

3 animals died due to blood collection trauma

Mortality:

mortality observed, treatment-related

Description (incidence):

3 animals died due to blood collection trauma

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

slightly higher final body weights in treatment groups, not statistically significant

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

slightly decreased in treatment groups, non-adverse

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

significant differences in organ/body weight ratios except for kidneys, adrenal glands and brain, non-adverse

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
Two control animals died on day 84. These deaths were related to blood collection. One female animal from the 10% dosage group also died from blood collection trauma. There were no other mortalities or clinical signs of toxicity.


BODY WEIGHT AND WEIGHT GAIN
The test animals had slightly higher final body weights than controls, but the differences were not statistically significant.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Food consumption among test animals was slightly lower than among the control animals.

HAEMATOLOGY
There were no outstanding differences in hematologic parameters among test and control animals

CLINICAL CHEMISTRY
There were no outstanding differences in clinical chemistry parameters among test and control animals

URINALYSIS
There were no outstanding differences in urinalysis parameters among test and control animals

NEUROBEHAVIOUR
No abnormal behavioural reactions were noted in the study.

ORGAN WEIGHTS
There were no significant differences in organ/body weight ratios except for kidneys, adrenal glands and brain. For these three organs, female test animals showed a higher organ/body weight ratio than control animals. All of these differences could be attributed to the slightly higher body weights observed in every test group rather than a deleterious effect of the test material. The absence of any abnormalities of these organs upon histopathologic examination would support this conclusion.

GROSS PATHOLOGY
No abnormalities were noted at gross examination.

HISTOPATHOLOGY: NON-NEOPLASTIC
Some minor histopathologic changes were noted among both the test and control animals, specifcially involving lesions in the trachea and lungs. These changes were judged to be due to spontaneous disease (potential pneumonia), and not related to the test material.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

>= 25 other: %

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: NOAEL corresponding to the highest dose tested

2

Dose descriptor:

NOAEL

Effect level:

>= 12 500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: NOAEL corresponding to the highest dose tested

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Oleic acid is practically nontoxic to rats in a repeated dose study when given doses of up to 25% in the diet. The NOAEL was ≥25% equivalent to ≥12500 mg/kg bw/day.