Isopropyl palmitate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

: lack of details on test substance; no urine analysis, no neurology, no ophthalmoscopy performed

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isopropyl myristate

EC Number:

203-751-4

EC Name:

Isopropyl myristate

Cas Number:

110-27-0

Molecular formula:

C17H34O2

IUPAC Name:

isopropyl myristate

Details on test material:

- Name of test material (as cited in study report): Isopropylmyristat; Myristinsäureisopropylester;
- Physical state: clear, odourless liquid
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Zentralinstitut für Versuchstierzucht, Hannover, Germany
- Age at study initiation: no data
- Weight at study initiation: mean ca. 150 g (females); ca. 195 g (males)
- Fasting period before study: no data
- Housing: 2-3 males per cage
- Diet (e.g. ad libitum): Altromin rat diet No. 1424 DK
- Water (e.g. ad libitum): yes
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): ca. 50
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/23

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
Dosing solutions were prepared freshly every day.
Dosing volume was 5 mL/kg bw.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily, 5 days per week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 500 and 1000 mg/kg/d
Basis:

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

- Rationale for selecting satellite groups:
5 additional animals per sex were for analysis of possible post-exposure reversibility of intoxication symptoms

Examinations

Observations and examinations performed and frequency:

CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION: No

FOOD EFFICIENCY: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at study termination
- Anaesthetic used for blood collection: Yes, ether
- Animals fasted: no data
- How many animals: all
- Parameters checked: Hct, Hb, erythrocyte count, leucocyte count, MCV, thromocyte count, differential leucocyte count

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at study termination
- Animals fasted: Yes, ether
- How many animals: all
- Parameters checked: Urea, Sodium, Potassium, Glucose, Calcium, ASAT, ALAT, gamma-Glutamyltransferase, Chloride, total protein, total cholesterol, anorganic phosphorus, AP

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

ORGAN WEIGHTS:
Thyroid gland, thymus, adrenal glands, spleen, heart, kidneys, brain, testes, liver

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, all animals
HISTOPATHOLOGY: Yes, ca. 33 organs of 5 male and 5 female animals of the highest dose group and of the control group were analyzed. Additionally all non-glandulary stomachs from all animals - including those of the recovery group 14 days after the last application - were histopathologically analyzed.
Histologically analyzed organs:
Eye, tongue, salivary gland, trachea, lung, Aorta thoracica, heart, maxillary and mesenterial lymph nodes, thymus, liver, spleen, pancreas, kidney, non-glandular stomach, glandular stomach, small and large intestine, urinary bladder, testes, epididymides, seminal vesicle, prostate, uterus, ovaries, thyroid gland, parathyroid gland, cerebellum, brain stem, cerebrum (hippocampus), sceletal muscle, peripher nerv, skin

Statistics:

t-test, U-test.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

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:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

not treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
No deaths occured and no signs of systemic toxicity were observed in any animals.

BODY WEIGHT AND WEIGHT GAIN
Control and test animals showed similar gain in body weight.

HAEMATOLOGY
No significant treatment-related changes observed.

CLINICAL CHEMISTRY
No significant treatment-related changes observed.

GROSS PATHOLOGY
No treatment related abnormalities observed.

HISTOPATHOLOGY: NON-NEOPLASTIC
Hyperplastic changes were found in the non-glandular stomach of treated and control animals. Manifest mucosal hyperplasia was found in animals of the highest dose group. In few cases the mucosal hyperplasia was found combined with a submucosal inflammatory oedema. In the recovery group these findings were not present in the non-glandular stomach, indicating the reversibility of the changes. The changes were judged to be induced by the olive oil used as vehicle and not by the test substance itself.
Therefore, no treatment-related changes were observed.

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects on: clinical signs; mortality; body weight; haematology; clinical chemistry; gross pathology; histopathology;

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In a 28 day oral gavage study a NOAEL of 1000 mg/kg/d was found for male and female Wistar rats.