Reaction products of furan-2,5-dione and octadec-1-ene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 2013-November 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

guideline study under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-[(2E)-octadec-2-en-1-yl]dihydrofuran-2,5-dione

Cas Number:

1628163-42-7

Molecular formula:

C22H38O3

IUPAC Name:

3-[(2E)-octadec-2-en-1-yl]dihydrofuran-2,5-dione

Constituent 2

Reference substance name:

3-[(2Z)-octadec-2-en-1-yl]dihydrofuran-2,5-dione

Molecular formula:

C22H38O3

IUPAC Name:

3-[(2Z)-octadec-2-en-1-yl]dihydrofuran-2,5-dione

Constituent 3

Reference substance name:

3-(octadecenyl)dihydrofuran-2,5-dione excluding 3-(2-octadecen-1-yl)dihydrofuran-2,5-dione

Molecular formula:

C22H38O3

IUPAC Name:

3-(octadecenyl)dihydrofuran-2,5-dione excluding 3-(2-octadecen-1-yl)dihydrofuran-2,5-dione

Constituent 4

Reference substance name:

Hexadecenylsuccinic anhydride

EC Number:

250-911-4

EC Name:

Hexadecenylsuccinic anhydride

Molecular formula:

C20H34O3

IUPAC Name:

3-(hexadecenyl)dihydrofuran-2,5-dione

Constituent 5

Reference substance name:

3-icosenylsuccinic anhydride

EC Number:

258-603-1

EC Name:

3-icosenylsuccinic anhydride

Molecular formula:

C24H42O3

IUPAC Name:

3-icosenyldihydrofuran-2,5-dione

Constituent 6

Reference substance name:

Side products from the reaction of octadec-1-ene and maleic anhydride

Molecular formula:

Not applicable - UVCB component

IUPAC Name:

Side products from the reaction of octadec-1-ene and maleic anhydride

Constituent 7

Reference substance name:

C16-20 (even numbered) alkenes (branched and linear)

Molecular formula:

C16H32, C18H36, C20H40

IUPAC Name:

C16-20 (even numbered) alkenes (branched and linear)

Constituent 8

Reference substance name:

Maleic anhydride

EC Number:

203-571-6

EC Name:

Maleic anhydride

Cas Number:

108-31-6

Molecular formula:

C4H2O3

IUPAC Name:

furan-2,5-dione

Test material form:

solid

Details on test material:

off-white solid, amber liquid at 80 °C. Expected to be stable for duration of testing; Expiration date: not applicable.

Specific details on test material used for the study:

As a result of increasingly rigorous criteria being applied to the analysis of commercial material used in physical property/toxicity testing, the identity of the material has been modified to reveal a more accurate and precise depiction of the commercial substance. This enhancement is reflected in changes in chemical identifiers such as EC and/or CAS numbers from those noted in earlier versions of data records or in study reports.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Number of Animals: 10
Sex: 5 females and 5 males. Females tested were nulliparous and nonpregnant.
Age/Body weight: Young adult (8-9 weeks)/males 269-280 grams and females 178-196 grams at experimental start.
Source: Received from SAGE Labs on Octoer 21, 2015.

Housing: The animals were singly housed in suspended stainless steel caging, and conformed to size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011).
An enrichment toy was placed into each cage. Little paper was placed beneath the cage and was changed at least three times per week.

Animal Room Temperature and Relative Humidity Ranges: 19-23 degrees C and 40-61%, respectively.
Animal Room Air Changes/Hour: 12 or 13. Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 8 days
Food: Envigo Teklad Global 16% Protein Rodent Diet #2016. The diet was available ad libitum.
Water: Filtered tap water was supplied ad libitum.
Contaminants: There were no known contaminants reasonably expected to be found in the water or food at levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Product Safety Labs.

Cage: Each cage was identified with a cage card indicating at least the study number and identification and sex of the animal.
Animal: A number was allocated to each rat on receipt and a stainless steel ear tag bearing this number to the animal. This number, together with a sequential animal number assigned to study 41876, constituted unique identification.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: 75% w/w mixture in mineral oil

Details on dermal exposure:

On the day prior to application, a group of animals was prepared by clipping the dorsal area and the trunk. After clipping and prior to application, the animals were examined for health, weighed (initial), and the skin checked for any abnormalities.
The test substance, as received, was a solid In order to ensure adequate contact with the skin, the test substance was applied as a dry paste (75% w/w mixture in mineral oil).
2000 mg/kg bw of test material was applied to a 2-inch x 3-inch, 4-ply gauze pad and placed on a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface). The gauze pad and entire trunk of each animal were then wrapped with 3-inch Duropore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rats were then returned to their designated cages. The day of application was considered day 0 of the study.

Duration of exposure:

Each test animal was exposed for 24 hours. After the 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed with a 3% soap solution followed by tap water and a clean paper towel to remove any residual test substance.

Doses:

All test animals received a similar dose of 2000 mg/kg bw. It was applied to a 2-inch x 3-inch area of the body.

No. of animals per sex per dose:

5 female rats and 5 male rats were used in the study. All animals received a similar dose of 2000 mg/kg of the test substance.

Control animals:

no

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths

Mortality:

The test substance caused no mortality in any of the animals tested.

Clinical signs:

other: There were no adverse clinical findings recorded for any animal over the course of the study.

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day study.

Any other information on results incl. tables

Animal No.	Sex	Body Weight (g)			Dose
		Initial	Day 7	Day 14	g
3201	M	269	310	345	0.72
3202	M	275	322	360	0.73
3203	M	280	356	399	0.75
3204	M	279	340	375	0.74
3205	M	280	317	348	0.75
3206	F	196	209	223	0.52
3207	F	187	199	224	0.50
3208	F	179	195	217	0.48
3209	F	190	202	234	0.51
3210	F	178	194	210	0.48

Animal Number	Findings	Day of Occurance
Males
3201	Active and Healthy Erythema at dose site	0(1-4.5 hrs), 7-14 1-6
3202	Active and Healthy Erythema at dose site	0(1-4.5 hrs), 2-14 1
3203	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 11-14 1-6 5-10
3204	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 9-14 1 2-8
3205	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 3-14 1 2-8
Females
3206	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 11-14 1 2-10
3207	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 11-14 1-2 3-10
3208	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 9-14 1-6 3-8
3209	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 10-14 1-6 3-9
3210	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 12-14 1-2 3-11

Animal Number	Tissue	Findings
Males
3201-3205	All tissues and organs	No gross abnormalities
Females
3206-3210	All tissues and organs	No gross abnormalities

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

Under the conditions of an OECD 402 guideline study, the single dose acute dermal LD50 of n-ODSA is greater than 2000 mg/kg bw in male and female rats.