Isooctyl palmitate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Isooctyl palmitate

EC Number:

215-675-9

EC Name:

Isooctyl palmitate

Cas Number:

1341-38-4

Molecular formula:

C24H48O2

IUPAC Name:

6-methylheptyl hexadecanoate

Test material form:

liquid

Remarks:

a colourless liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

The test was initially conducted with the dose of 50 mg.Kg-1 of body weight, six steps at the dose levels of 50, 300 and 2000 mg.Kg-1 of body weight.. This starting dose was based on historical information from studies carried out with the same active ingredient and data from literature. The time interval between treatment groups was determined according to the duration and severity of signs of toxicity.

No. of animals per sex per dose:

Eighteen females, divided in groups of three animals, were tested in six steps at the dose levels of 50, 300 and 2000 mg.Kg-1 of body weight.
50 mg.Kg-1: 6
300 mg.Kg-1: 6
2000 mg.Kg-1: 6

Details on study design:

Dose Level

The test was initially conducted with the dose of 50 mg.Kg-1 of body weight, following the flowchart shown in Appendix 1. This starting dose was based on historical information from studies carried out with the same active ingredient and data from literature. The time interval between treatment groups was determined according to the duration and severity of signs of toxicity.

Animal’s Weighing

The rats were weighed on day of the administration of the test item (Day 0) and later on days 7 and 14. At the beginning of the test, the weights between the animals in a test group varied, but not exceeded the average weight of ± 20%.

Test Item Administration

The feed supplied to the animals was interrupted at the end of the day previous to the application of the test item. The volume of test item administered to each animal was calculated according to the body weight determined on the day of treatment. The test item was applied pure. The administration was performed by gavage, using a suitable metal cannula attached to a syringe. Animals were returned to ad libitum feeding 3 hours after dosing.


Clinical Examinations

The animals were examined for death and systemic signs of toxicity with special attention during the first 4 hours after dosing and during 14 days after the test item application. Observations included but not limited at: changes in skin and fur, eyes and mucous membranes alteration in respiratory, circulatory, autonomic and central nervous system and somatomotor activity. Particular attention was done to apparition of convulsions, salivation, lethargy, tremors, diarrhea, coma and death. All observations were registers.


Euthanasia

At the end of the observation period, all animals were weighed and euthanized in a carbon dioxide chamber. A second method of euthanasia (cervical dislocation) was realized to confirm the death of the animal.

Necropsy

All test animals euthanized at end each step were subjected to necropsy. This included a minute examination of the external body surface, all orifices, thorax, pelvic and abdominal cavities and contends. All the alterations were registers for each animal.

Results and discussion

Preliminary study:

All the animals exposed to the test item by the oral route at the doses of 50, 300 and 2000 mg.Kg-1 of body weight presented no systemic signs of toxicity

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

0

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the test conditions, the test item Isooctyl palmitate, when administered by oral route in female rats, did not cause deaths, for every step taken at the dose levels of 50, 300 and 2000 mg.Kg-1 of body weight. In clinical examinations, the tested animals did not show systemic signs of toxicity. In macroscopic evaluations no alterations were observed during the necropsies. Based on the flow chart with the starting dose of 50 mg.Kg-1 of body weight, the test item was classified as category 5 (unclassified), according to the GHS (Globally Harmonized Classification System for Chemical Substances and Mixtures). The oral LD50 value of test item Isooctyl palmitate, for female rats, was estimated to be greater than 5000 mg.Kg-1 of body weight.

Executive summary:

This acute oral toxicity study in rats(Rattus norvegicus)was carried out in order to evaluate the possible toxic effectsof the test itemIsooctyl palmitateadministered by the oral route. Eighteen females, divided in groups of three animals, were tested insixsteps at thedose levels of 50, 300 and 2000mg.Kg^-1of body weight.The test item was applied pure.The volume administered to each animal was calculated according to the body weight determined on the day of treatment.Afterdosing by gavage, the animals were observedduring 14 days to evaluatedeaths, and behavioral and clinical alterations. The test item administered by oral route for femalerats did not cause treatment-related deaths in any of the steps at the dose levels of50, 300 and 2000mg.Kg^-1of body weight. At the clinical examinations, toxicity signs were not observed.The animals were euthanized in the end of the observation period and were submitted to necropsies, where they did not present macroscopic alterations oracute toxic effects caused by test item.Based on the flow chart with the starting dose of50mg.Kg^-1body weight, the test item was classified as category 5 (unclassified), according to the GHS (Globally Harmonized Classification System for Chemical Substances and Mixtures).The acute oral LD₅₀value ofthetest itemIsooctyl palmitatewas estimated >5000mg.Kg^-1of body weightfor female rats.