Phosphorous ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009/03/17 to 2009/03/24

Reliability:

1 (reliable without restriction)

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The temperature was recorded out of the target range (20 ± 3 ºC) as 16.3-20.4°C .The deviation of the temperature had no presumed effect on the study.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

esterification products of castor oil and polyphosphoric acids

EC Number:

614-406-6

Cas Number:

68308-61-2

Molecular formula:

C57H107P3O18

IUPAC Name:

esterification products of castor oil and polyphosphoric acids

Details on test material:

- Name of test material (as cited in study report): GARDO TP10451
- Physical state: liquid
- Analytical purity: 100%
- Lot/batch No.: 2939R
- Expiration date of the lot/batch: 2010-02-18

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sándor Ferenc 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: 16-17 weeks
- Weight at study initiation: 3600-4261 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): The animals received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum.
- Water (e.g. ad libitum): The animals received tap water from the automatic watering system ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16.3 - 20.4 °C
- Humidity (%): 30 - 59 %
- Air changes (per hr): 15-20 air exchange/hour

IN-LIFE DATES: From: 2009/03/17 To: 2009/03/24

Test system

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

The test item was used undiluted, as a single dose of 0.5 mL of GARDO TP10451, applied to the test area. The untreated skin of each animal served as a control.

Duration of treatment / exposure:

After 4 hours, the remaining test item was removed with water of body temperature.

Observation period:

To assess skin irritation, animals were examined at 1, 24, 48, 72 hours and 1 week after the patch removal. Additional general examinations were performed daily.

Number of animals:

3 animals

Details on study design:

TEST SITE
The test item was applied to an area of approximately 6 cm² of intact skin. Sterile gauze pads were placed on the skin of rabbits. These gauzes were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The entire trunk of the animals was wrapped with plastic wrap for 4 hours.

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 (injures in depth) 4
Total possible Erythema score: 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised appr. 1 mm) 3
Severe oedema (raised more than 1 mm
and extending beyond area of exposure) 4
Total possible Oedema score: 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

9918/M

Time point:

other: 1 h, 24 h, 48 h, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

9914/M

Time point:

other: 24 h, 48 h, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

2645/M

Time point:

other: 1 h, 24 h, 48 h, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h, 48 h, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

9918/M

Time point:

other: 24 h, 48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

9914/M

Time point:

other: 24 h, 48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

2645/M

Time point:

other: 24 h, 48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 h, 48 h, 72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

NA

Other effects:

NA

Any other information on results incl. tables

There was no mortality or systemic clinical changes related to GARDO TP10451 administration.

There was no effect of treatment on body weight.

At observation one hour after patch removal, very slight erythema (score 1) was observed in two animals (No.: 9918, 2645).

At 24 and 48 hours after patch removal, very slight erythema (score 1) and very slight oedema (score 1) was noted in all animals.

At 72 hours after patch removal, very slight erythema (score 1) was observed in all animals.

At 1 week after patch removal, there were no observed signs noted on the skin of the treated animals.

As no clinical signs were observed up to 1 week after patch removal, the study was terminated after the 1 week post-dosing observations.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 1.00, 1.00 and 1.00 respectively.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.67, 0.67 and 0.67 respectively.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: Directive 2001/59/EC and the UN Globally Harmonised System of Classification and Labelling of Chemicals

Conclusions:

Under the conditions of this acute skin irritation/corrosion study with rabbits, the test item GARDO TP10451 did not cause any skin irritating effect.

Executive summary:

The acute skin irritation study of GARDO TP10451 was performed in albino New Zealand White rabbits. The irritation effect of the test item was evaluated according to the Draize method (OECD No.: 404, 2002).

The test item was administered undiluted, at a single dose of 0.5 mL. Gauze was placed onto the hairless skin of the rabbit, test item was applied to the gauze, additional gauze was placed over the test item and an adhesive clear plastic patch applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control.

After 4 hours, the remaining test item was removed with water of body temperature.

To assess skin irritation, animals were examined at 1, 24, 48, 72 hours and 1 week after the patch removal. Additional general examinations were performed daily.

There was no mortality or systemic clinical changes related to GARDO TP10451 administration.

There was no effect of treatment on body weight.

At observation one hour after patch removal, very slight erythema (score 1) was observed in two animals.

At 24 and 48 hours after patch removal, very slight erythema (score 1) and very slight oedema (score 1) was noted in all animals.

At 72 hours after patch removal, very slight erythema (score 1) was observed in all animals.

At 1 week after patch removal, there were no observed signs noted on the skin of the treated animals.

As no clinical signs were observed up to 1 week after patch removal, the study was terminated after the 1 week post-dosing observations.