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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 2015- 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:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

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:

rabbit

Strain:

other: New Zealand albino

Details on test animals or test system and environmental conditions:

Housing: The animals were singly housed in suspended stainless steel caging,which conforms to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Enrichment (e.g., toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
Animal Room Temperature and Relative Humidity Ranges: 19-23ºC and 40-60%, respectively
Animal Room Air Changes/Hour: 12.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 21 or 28 days
Food: EnvigoTeklad Global High Fiber Rabbit Diet®#2031. A designated amount of the diet (approximately 150 grams/day) and a Premium Timothy Cube (TM) (Ontario Dehy Inc.) were available to each rabbit.
Water: Filtered tap water was supplied adlibitum.

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 rabbit on receipt and a stainless steel ear tag bearing this number was attached to the animal. This number, together with a sequential animal number assigned to study 41878, constituted unique identification.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: 75 % w/w mixture in mineral oil

Controls:

no

Amount / concentration applied:

Five-tenths of a gram of the test substance (0.67g of the prepared test mixture) was placed on a 1-inch x 1-inch, 4-ply gauze pad and applied to one 6-cm2 intact dose site on each animal. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit and they were returned to their designated cages.

Duration of treatment / exposure:

After 4 hours of exposure to the test substance, the pads and collars 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.

Observation period:

Individual dose sites were scored according to the Draize scoring system at approximately 30-60 minutes, 24, 48, and 72 hours and 7, 10 and 14 days after patch removal

Number of animals:

3 female rabbits were used. They were nulliparous and non-pregnant.

Details on study design:

On the day before application, a group of animals was prepared by clipping the dorsal area and the trunk. On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. Three healthy, naive animals (not previously tested) without pre-existing skin irritation were selected for test.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24 h

Score:

3.7

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks:

reversible

Remarks on result:

probability of moderate irritation

Results 2

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

48 h

Score:

3

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks:

reversible

Remarks on result:

probability of moderate irritation

Results 3

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

72 h

Score:

3

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks:

reversible

Remarks on result:

probability of moderate irritation

Results 4

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

7 d

Score:

1

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks:

reversible

Remarks on result:

probability of mild irritation

Results 5

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

10 d

Score:

0.3

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks:

reversible

Remarks on result:

probability of weak irritation

Results 6

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

14 d

Score:

0

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks:

reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The Primary Dermal Irritation Index (PDII) calculated for this test substance was 3.2.

Other effects:

Over the first 48 hours after patch removal, all three treated sites exhibited well-defined to moderate to severe erythema and very slight to slight edema. The overall incidence and severity of irritation decreased gradually with time. Desquamation was noted at all three dose sites on Days 7 and 10. All animals were free of dermal irritation by Day 14 (study termination).

Any other information on results incl. tables

Animal No.	Sex	Time After Patch Removal
		30-60 mins	24 hrs	48 hrs	72 hrs	Day 7	Day 10	Day 14
3501	F	2/1	2/2	2/0	2/0	1/0	0/0	0/0
3502	F	2/1	2/2	3/2	3/2	2/0	1/0	0/0
3503	F	2/1	2/1	2/0	2/0	0/0	0/0	0/0
Total		6/3	6/5	7/2	7/2	3/0	1/0	0/0
Mean		2.0/1.0	2.0/1.7	2.3/0.7	2.3/0.7	1.0/0.0	0.3/0.0	0/0

Summed values used for evaluation of irritation:

	Time After Patch Removal
	30-60 min	24 hrs	48 hrs	72 hrs	Day 7	Day 10	Day 14
Erythema	2.0	2.0	2.3	2.3	1.0	0.3	0.0
Edema	1.0	1.7	0.7	0.7	0.0	0.0	0.0
Total (PDI^2)	3.0	3.7	3.0	3.0	1.0	0.3	0.0

The average value was calculated to be 3.2.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

Migrated information: Irritation scores are > 2.3 and < 5 for 2 of 3 animals at 24, 48 and 72 hours after application.

Conclusions:

n-ODSA EC 701-338-8 is moderately irritating to skin according to the Draize scale. The substance is classified as a skin irritant, Category 2.