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Toxicological information

Repeated dose toxicity: oral

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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (limited details on test substance purity, lack of urine analysis, neurology and ophthalmoscopy.

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:
limited details on test substance purity, no urine analysis, no neurology, no ophthalmoscopy performed
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Isopropyl myristate
EC Number:
203-751-4
EC Name:
Isopropyl myristate
Cas Number:
110-27-0
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: Altromin rat diet No. 1424 DK, ad libitum
- Water: yes, ad libitum
- 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:
100, 500 and 1000 mg/kg bw/day
Basis:
actual ingested
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 bw/day was found for male and female Wistar rats.