Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015-03-27 - 2015-05-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study OECD 404, GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The dosing regimen was modified due to the severity of the responses observed following the 3-minute and 1-hour exposures on the initial animal.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Remarks:
Homogenous Liquid
Specific details on test material used for the study:
Trade name: CYPHOS IL 101 Phosphonium Salt
Physical state: liquid
Composition of test material, percentage of components: Trihexyl(tetradecyl)phosphonium chloride (258864-54-9), > 95%
Lot/batch No.: WEC031280
Expiration date of the lot/batch: >1 year when stored at room temperature and protected from direct contact with water (hydrophobic)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products inc. Denver, PA
- Age at study initiation: 18-19 weeks old
- Weight at study initiation: 2.5 kg
- Housing: individually housed in a suspended metal cage
- Diet: Fresh PMI Rabbit Chow (Diet#5321) was provided daily
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: temperature controlled
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: A volume of 0.5 mL per site
Duration of treatment / exposure:
Site #1: 3 minutes
Site #2: 1 hour
Residual test article was removed with dry gauze
Observation period:
Site #1: Immediately and at 1 hour following the patch removal for the 3 minute exposure, and at 24, 48 and 72 hours and on Day 7 and 14.
Site #2: At 1 hour following patch removal for the one-hour exposure, and at 24, 48 and 72 hours and on Day 7 and 14.
Number of animals:
1 (female)
Details on study design:
TEST SITE
- Area of exposure: On the day before the test, the dorsal area of the trunk of the animal was clipped free of hair.
- % coverage: Each dose site was approximately 6 square cm (2.5 x 2.5 cm).
- Type of wrap if used: The test material, was introduced under a 2 cm X 3 cm cotton gauze patch. The patch was secured in position with a peice of porous dressing large enough to cover dose site with at least 5 cm square to spare on all sides of the gauze patch. To prevent the animal interfering with patch, the trunk was wrapped with a porous and non-irritating tape, and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Both sites were gently wiped with dry gauze to remove residual test article

SCORING SYSTEM: Erythema and edema were scored according to the Draize scoring system.
The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction.

Erythema formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4
Maximum possible: 4

Edema formation
No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges of area well-defined by definite raising): 2
Moderate edema (raised approximately 1.0 mm): 3
Severe edema (raised more than 1.0 mm, extending beyond area of exposure): 4
Maximum possible: 4

The body weight of the animal was recorded pretest and at the study termination. The animal was observed for toxicological and pharmacological effects at each dermal observation period and observed for mortality daily. The animal was humanely sacrificed using CO2 following study termination.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
3-minute exposure
Time point:
other: Immediately
Score:
1
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
3-minute exposure
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
3-minute exposure
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
1-hour exposure time
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: necrosis
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
1-hour exposure time
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
See Table 1. corrosive effects were observed (see Other effects for more details)

- Three-minute exposure: Immediately following the exposure, erythema was very slight and edema was absent. One hour following exposure, erythema was well-defined and edema was slight. 24, 48, and 72 hours post-exposure, erythema and edema were severe. On Day 7 and 14, erythema was severe and edema was moderate; severe eschar formation was observed.

- One-hour exposure: One hour following exposure, erythema was moderate to severe and edema was moderate; shiny areas were observed. 24 hours post-exposure, erythema and edema were severe; pale areas were observed. 48 and 72 hours post-exposure, erythema and edema were severe; moderate eschar formation and pale areas were observed. On Day 7, erythema was severe and edema was moderate, necrotic, cracking, and flaking skin and dark areas were observed. By Day 14, erythema was severe and edema was moderate, necrotic and flaking skin and shiny areas were observed.

- Other adverse systemic effects: No abnormal physical signs were observed. The animal gained weight by study termination

Any other information on results incl. tables

Immediately following patch removal 1 hour 24 hours 48 hours 72 hours 7 days 14 days
Site #1: 3-minute exposure Erythema 1 2 4 4 4 >4s >4s
Edema 0 2 4 4 4 3 3
Site #2: 1-hour exposure Erythema n.o. 3,s 4,p >4m,p >4m,p >4n,c,d,f >4n,f,s
Edema n.o. 3 4 4 4 3 3

n.o. - not observed; >4s = severe eschar; >4m = moderate eschar; >4n = necrosis

c = craking skin; d = dark area; f = flaking skin; p = pale areas; s = shiny areas

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Under the conditions of this study (in vivo skin irritation test according to OECD guideline 404), Trihexyltetradecylphosphonium chloride was determined to be corrosive to skin. Based on these results, the test item is considered Category 1B according to GHS critera.
Executive summary:

In a primary dermal irritation study, a young adult New Zealand White rabbit (female) was dermally exposed to 0.5 mL of Trihexyltetradecylphosphonium chloride. Two test sites were covered with a semi-occlusive dressing for an exposure period of three minutes on site#1 and 1 hour on site #2. Skin reactions were assessed immediately and at 1 hour after patch removal. Reactions were scored again at 24, 48 and 72 hours and on Days 7 and 14 following patch removal for both sites.

Three-minute exposure: 24, 48, and 72 hours post-exposure, erythema and edema were severe. On Day 7 and 14, erythema was severe and edema was moderate; severe eschar formation was observed.

One-hour exposure: 24, 48 and 72 hours post-exposure, erythema and edema were severe. On Day 7, erythema was severe and edema was moderate, necrotic, cracking, and flaking skin and dark areas were observed. By Day 14, erythema was severe and edema was moderate, necrotic and flaking skin and shiny areas were observed.

Given these results, Trihexyltetradecylphosphonium chloride is corrosive and classified in GHS Category 1B.