Amines, C12-14-alkyl, isooctyl phosphates

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 November 1999 to 6 December 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do no effect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Amines, C12-14-alkyl, isooctyl phosphates

EC Number:

269-119-5

EC Name:

Amines, C12-14-alkyl, isooctyl phosphates

Cas Number:

68187-67-7

Molecular formula:

C19H42NPO4 - C29H63NPO4

IUPAC Name:

Amines, C12-14-tert-alkyl, isooctyl mono phosphates

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: New Zealand White rabbits were supplied by Charles River UK Ltd, Margate, Kent, England.
- Age at study initiation: at least 14 weeks old
- Weight at study initiation: At the start of the study the animals weighed 2.8 to 3.1 kg
- Housing: The animals were individually housed in stainless steel cages with perforated floors.
- Diet (e.g. ad libitum): Free access to a standard laboratory rabbit diet (Special Diet Services, Stanrab (P) SQC pellet) was allowed throughout the study. Hay three times / week.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: Twenty days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 21°C
- Humidity (%): 28 to 52%
Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (0700 - 1900 hours) and twelve hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 ml of the test substance was administered as supplied

Duration of treatment / exposure:

4 hours

Observation period:

1 hour, 24 hours, 48 hours, 72 hours and on Days 5 to 14.

Number of animals:

3 males

Details on study design:

PROCEDURE:
Approximately 24 hours before the test item application, each rabbit was clipped free of hair from the dorso-lumbar region using electric clippers exposing an area of skin approximately 100 mm x 100 mm.

Approximately 0.5 ml of the test item was applied under a 2-ply 25 mm x 25 mm porous gauze pad to one intact skin site on each animal. Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.

At the end of the exposure period the semi occlusive dressing and gauze were removed from each animal and the treatment site washed with warm water to remove any residual test item. The treated area was blotted dry with absorbent paper.

Examination of the treated skin was made approximately 1 hour following removal of the dressings and 24, 48 and 72 hours after exposure. Additional observations were made for all animals on Days 5 through to 14. Local dermal irritation was assessed using the numerical system, see any other information on materials and methods

Any other skin reactions if present, were also recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

3687

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Necrotic patch

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

3687

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

3688

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Necrotic patch

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

3688

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

3869

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Necrotic patch

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

3869

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Please see attached background information for individual skin reactions.

Severe erythema with slight to moderate oedema and necrotic patches were seen in all three animals. The necrotic patches began sloughing off in two animals on Day 11 revealing new skin underneath. Blanching of the skin and desquamation (characterised by dryness of the skin) were observed in all animals. Reactions gradually ameliorated however very slight to well defined erythema with or without very slight oedema was still evident in all animals at study termination on Day 14.

Other effects:

There were no other signs of toxicity or ill health.

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

A single semi occlusive application of the test substance to intact rabbit skin for four hours elicited severe dermal irritation with necrotic patches.
The test item meets the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 17 July 1992)

- Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 92/69/EEC

- EPA Health Effects Test Guidelines OPPTS 870.2500 Acute Dermal Irritation EPA 712 -C-98 -196 (August 1998)

Results. 

A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits for four hours elicited severe dermal irritation with necrotic patches.

Conclusion. 

The test item is classified as corrosive according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.