Amines, C11-14-branched alkyl, monohexyl and dihexyl phosphates

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 23, 1981 - December 7, 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with restrictions (study was performed under QAU): - occlusive conditions - exposure period of 24 hours

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(occlusive conditions, exposure period of 24 hours)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: United States Environmental Agency (EPA) § 163.81-5 "Primary dermal irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amines, C11-14-branched alkyl, monohexyl and dihexyl phosphates

EC Number:

279-632-6

EC Name:

Amines, C11-14-branched alkyl, monohexyl and dihexyl phosphates

Cas Number:

80939-62-4

Molecular formula:

Unspecified

IUPAC Name:

Amines, C11-14-branched alkyl, monohexyl and dihexyl phosphates

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Weight at study initiation: 2 to 3 kg
- Housing: individually in metal cages
- Diet (ad libitum): standard rabbit food - NAFAG, No. 814
- Water (ad libitum): drinking water
- Acclimation period: min. of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

occlusive

Preparation of test site:

other: shaved (one flank), shaved and scarified (other flank)

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 male ande 3 female animals

Details on study design:

TEST SITE
- Area of exposure: both side flanks (one side was just shaved, the other one was shaved and scarified)
- Type of wrap if used: gauze patch (2.5x2.5 cm), patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape.

SCORING SYSTEM:
Erythema and eschar 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
Total possible erythema score: 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 mm) 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) 4
Total possible edema score: 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h- 48 h - 72 h

Score:

2.83

Max. score:

4

Reversibility:

not fully reversible within: 14 days (all animals were affected)

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 h - 48 h - 72 h

Score:

2.5

Max. score:

4

Reversibility:

not fully reversible within: 14 days (all animals were affected)

Results 3

Irritation parameter:

primary dermal irritation index (PDII)

Score:

5

Max. score:

8

Remarks on result:

other: The scores read after 24 and 72 hours for erythema and edema for the intact as well as for the abraded skin were summed up and divided by 4 (FHSLA § 191.11): The test substance caused a marked irritation when applied to intact and abraded rabbit skin.

Irritant / corrosive response data:

The following observations were made in practically all the application sites in the course of the experiment, in addition to the scores: erythema greater than the surface of compound patch, ischaemic areas, cracked skin, scales formation.

Other effects:

Besides transient periods of anorexia in few animals no other symptoms were observed. One female animal died at day 8 of test independently of the compound administration. No gross lesions were found.

Any other information on results incl. tables

In the following tables, only the results of the treatment of the intact skin side is given, as testing on intact skin is recommended by OECD guideline 404 and the basis for skin irritation assessment.

Table 1: Evaluation of erythema an edema in male animals after a 24 hours treatment under occlusive conditions:

Observation time	Animal	Erythema	Edema
24 hours	1	3	3
	2	2	2
	3	3	3
48 hours	1	3	3
	2	3	2
	3	3	3
72 hours	1	4	4
	2	3	2
	3	4	3
14 days	1	4	4
	2	3	2
	3	4	3
Mean (24-48-72h)	1	3.33	3.33
	2	2.66	2
	3	3.33	3
Mean		3.11	2.78

Table 2: Evaluation of erythema an edema in female animals after a 24 hours treatment under occlusive conditions:

Observation time	Animal	Erythema	Edema
24 hours	1	2	2
	2	2	2
	3	3	2
48 hours	1	2	2
	2	3	3
	3	3	2
72 hours	1	2	2
	2	3	3
	3	3	2
14 days	1	dead	dead
	2	4	3
	3	4	3
Mean (24-48-72h)	1	2	2
	2	2.66	2.66
	3	3	2
Mean		2.55	2.22

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present experiment the test article was found to cause a marked irritation when applied to intact and abraded rabbit skin.