Trihexadecyl citrate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 March 1993 - 17 March 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not applicable

Principles of method if other than guideline:

Minimal erythemal level dosage selection test: 5 guinea pigs were tesed for irritation reactions (erythema and oedema) following a 6 hour dermal exposure to the test article in a vehicle and unchanged on a gauze patch.
Main irradiation test: 10 guinea pigs were tested for irritation reactions (erythema and oedema) following a 30 minute exposure to the test article unchanged and in dilution with UVA irradiation. A control group was treated with the test article in the same way but nor irradiated.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Trihexadecyl citrate

EC Number:

224-931-9

EC Name:

Trihexadecyl citrate

Cas Number:

4560-68-3

Molecular formula:

C55H106O6

IUPAC Name:

trihexadecyl citrate

Test material form:

liquid

Specific details on test material used for the study:

Appearance: Clear liquid
Storage: Ambient temperature and humidity

Test animals

Species:

guinea pig

Strain:

Hartley

Details on test animals or test system and environmental conditions:

Species: Guinea Pig
- Strain: Hartley derived
- Sex: Male and Female
- Weight Range: 300 — 500 grams at study initiation.
- Supplier: Gingrich Animal Supply, Fredricksburg, Pa 17026, USDA # 23-B-007
- Acclimation: Animals were acclimated to the testing facility at least seven days prior to the start of testing. Animals were observed for general health and suitability for testing during this period.
- Housing: Animals were group housed in suspended stainless steel, wire mesh cages in an environmentally controlled room.
- Diet: Water and standard laboratory guinea pig feed were available ag libitum.
- Identification: All animals placed on test were identified by color coding and cage labels.

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: in Mineral oil and unchanged

Controls:

yes

yes, concurrent vehicle

Amount / concentration applied:

Minimal erythemal level dosage selection: 0.5 ml
Irradiation phase: 0.1 ml

Duration of treatment / exposure:

Minimal erythemal level dosage selection: 30 mins
Irradiation phase: 30 mins

Observation period:

Minimal erythemal level dosage selection: 24 hours
Irradiation phase: 24 hours

Number of animals:

Minimal erythemal level dosage selection: 5
Irradiation phase: 10

Details on study design:

Minimal Ervthemal Level (MEL) Dosage Selection:
The following procedure was utilized to evaluate a potential dose related irritation response produced by the product at various concentations. In order to determine the test concentration to be used in the study, the backs of 5 guinea pigs were shvaved closely approximately 18-24 hours prior to dosing, using electric clippers. The area was then depilated using a thioglycolate preparation (NAIR). Three dilutions of test material, 75%, 50% and 25%, were prepared in mineral oil. One application of 0.5 ml of each dilution and of test material at 100% was placed on gauze patches. The patches were then placed in a row on either side of the spinal column. The area was occluded with Demaclear tape and a plastic sheet, then overwrapped with Elastikon tape to hold patches in place and form an occluded wrap. After a six hour exposure, the patches were removed. The sites were scored within 30 — 60 minutes after patch removal and again at 24 hours after application for erythema and/or edema. Skin reactions are graded based on the Draize Scoring Table for Skin Reactions The highest concentration which produced no irritation was the 75% concentration. However, one animal had very slight erythema at the 100% concentration, therefore that dose level was chosen for the highest testing concentration.
Three lower concentrations of 75%, 50% and 25% were applied so that a total of four concentrations of the test material were utilized for the irradiation phase.

Irradiation Phase:
10 guinea pigs for the test group were prepared as described above. The pigs were placed in holding cages. An adhesive backed patch of closed cell foam with pre—cut holes was applied to the backs of each pig in both the test and control groups. 0.1 ml of decreasing concentrations based on the results of the MEL were placed in each of the four wells. The sample was left in place for 30 minutes after which the test group was irradiated with four General Electric Model F4OBL Lamps (emission 310—400nm) equipped with a window glass filter to eliminate radiation below 320 nm.
- Control Group: One group of 10 animals was prepared and dosed as per the test group, except that the control animals were not irradiated.
- Vehicle Control Group: One group of 5 animals was prepared as per the test group and was dosed with 0.1 ml of Mineral Oil at 100% concentration and irradiated as per the test group.
- Observations: Skin reactions were scored one hour and 24 hours after irradiation using the Draize Scoring table for Skin Reactions.
- Observation: Animals were examined for signs of erythema, edema and any lesions or other toxic effects.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.2

Max. score:

1

Reversibility:

not specified

Remarks on result:

other: Minimal Erythemal Level Dosage Selection group

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: UVA irradiated group

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: UVA irradiated group

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: no UVA control group

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: no UVA control group

Irritant / corrosive response data:

- Minimal erythemal level dosage selection: The highest concentration which produced no irritation was the 75% concentration. However, one animal had very slight erythema at the 100% concentration, therefore that dose level was chosen for the highest testing concentration. Three lower concentrations of 75%, 50% and 25% were applied so that a total of four concentrations of the test material were utilized for the irradiation phase.
- UVA irradiation Test Group: In the irradiated group, none of the animals exhibited erythema or edema at one hour or twenty four hours post exposure.
- UVA Control Group: In the nonirradiated group, none of the animals exhibited erythema or edema at any of the readings.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test article was determined not to be a skin irritant under the conditions of the test.

Executive summary:

The test material, was dosed in a group of ten (5 male and 5 female) guinea pigs and then placed under UV light (emission 310-400nm), for a period of two hours. One animal exhibited very slight erythema at the 100% concentration test site one hour post dosing which cleared by 24 hours.