Esterification products of dihydrofuran-2,5-dione, C16-24 (even numbered) alkenyl with propane-1,2,3-triol and propane-1,2,3-triol oligomers

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 2 April 2014 to 16 April 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: There were no deviations (unplanned changes) from the study plan.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Esterification products of dihydrofuran-2,5-dione, C16-24 (even numbered) alkenyl with propane-1,2,3-triol and propane-1,2,3-triol oligomers

EC Number:

940-875-4

Molecular formula:

C3H8O3 - C99H182O20

IUPAC Name:

Esterification products of dihydrofuran-2,5-dione, C16-24 (even numbered) alkenyl with propane-1,2,3-triol and propane-1,2,3-triol oligomers

Test material form:

other: viscous amber liquid

Details on test material:

Purity: not supplied
Physical state / Appearance: amber colored extremely viscous liquid
Expiry date: 08 August 2014
Storage Conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

The study was designed and conducted to cause the minimum suffering or distress to the animals consistent with the scientific objectives and in accordance with the Harlan Laboratories Ltd, Shardlow, UK policy on animal welfare and the requirements of the United Kingdom's Animals
(Scientific Procedures) Act 1986 Amendment Regulations 2012. The conduct of the study may be reviewed, as part of the Harlan Laboratories Ltd, Shardlow, UK Ethical Review Process.
The study was conducted in accordance with the UK Home Office Guidance document on Regulatory Toxicology and Safety Evaluation Studies and the OECD guidance document on recognition, assessment and use of clinical signs as humane endpoints for experimental animals used in safety evaluation.
The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair. The calculated volume of test item, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. The animals were caged individually for the 24-Hour exposure period.
Shortly after dosing the dressings were examined to ensure that they were securely in place.

Duration of exposure:

24 Hours

Doses:

Test item at a dose level of 2000 mg/kg.

No. of animals per sex per dose:

5

Details on study design:

The animals were observed for deaths or overt signs of toxicity V2, 1,2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored. Any other skin reactions, if present were also recorded.
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

No signs of systemic toxicity were noted during the observation period.

Body weight:

One female showed body weight loss during the first week with expected gain in body weight during the second week. Two females showed expected gain in body weight during the first week but body weight loss or no gain in body weight during the second week. The remaining animals showed expected gains in body weight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Very slight erythema and very slight edema were noted at the test sites of all females one day after dosing. Light brown discoloration of the epidermis was noted at the test sites of males one and two days after dosing.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute dermal median lethal dose ( LD 50 ) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Executive summary:

Test Guideline

OECD Guideline 402, EC Method B3

Method

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality: There were no deaths.

Clinical Observations: There were no signs of systemic toxicity.

Dermal Irritation: Very slight erythema and very slight edema were noted at the test sites of all females one day after dosing. Light brown discoloration of the epidermis was noted at the test sites of males one and two days after dosing.

Body Weight: One female showed body weight loss during the first week with expected gain in body weight during the second week. Two females showed expected gain in body weight during the first week but body weight loss or no gain in body weight during the second week. The remaining animals showed expected gains in body weight over the study period.

Necropsy: No abnormalities were noted at necropsy.

Conclusion: The acute dermal median lethal dose ( LD 50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.