Diphosphoric acid, compd. with piperazine (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 March to 6 March 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

457-330-7

EC Name:

-

Cas Number:

66034-17-1

Molecular formula:

Hill formula: C4H10N2:H4O7P2 CAS formula: C4H10N2:H4O7P2

IUPAC Name:

(phosphonooxy)phosphonic acid; piperazine

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species: SPF bred New Zealand White albino rabbits
Supplier: Centre Lagro, France
Sex and age: males, young adult, ca 9 weeks old
Date of arrival: 26 February 2003
Quarantine/acclimatization: 5 days
Body weights at start of study: 1716, 1778 and 1895 g
Body weights at termination: 1775, 1850 and 1937 g
Caging: individually in stainless steel cages with perforated floor
Lighting: 12 hours light/12 hours dark cycle
Temperature during testing: 20± 3 °C.
Relative humidity during testing: 30-70%. Upper limit incidentally up to 99.9%, because of meteorological circumstances and/or wet cleaning of the animal room.
Ventilation: ca 10 air changes/hour
Diet/water: standard laboratory diet ad libitum. Each batch of this diet is analysed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are kept available in the archives. Tap water (N.V. Hydron MiddenNederland) ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are kept available in the archives. The results of diet and water analyses were considered acceptable for this study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

0.5 g of the test substance and moistened with 0.5 ml of water.

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

Upon arrival, the rabbits were checked for overt signs of ill health and anomalies. Three days prior to the start of the study, the hair was removed from the back and flanks of the animals using electric clippers in a way as to avoid abrasions. The clipping was repeated if considered necessary. The study was carried out with three rabbits. The rabbits were treated as follows: just prior to application, a skin site suitable for application was selected on the clipped flank of the animal. A plastic cup with a diameter of circa 2.5 cm was loaded with an amount of 0.5 g of the test substance and moistened with 0.5 ml of water. The cup loaded with the test mixture was fixed to the selected application site by means of semi-occlusive, adhesive tape (Leukopor, BDF, Germany). Subsequently, the entire trunk of the rabbit was wrapped with a self-adhesive-gauze (Fixomull, BDF, Germany) to maintain the cup in position and to retard evaporation of volatile substances. The gauze was additionally fastened with two strips of tape (Leukoflex, BDF, Germany). After a 4-hour exposure period, the test substance and cup were removed and the test site was cleaned with a tissue moistened with water. One hour after treatment, the resulting skin reactions were evaluated by the method of Draize et al. (J. Pharmacol. Exp. Ther. 82 (1944) 377-390). Further skin readings were made at approximately 24, 48, and 72 h after treatment.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48 & 72h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48 & 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

At 1, 24, 48 and 72 h after removal, no signs of skin irritation (erythema, edema) were observed in any of the three rabbits.

Any other information on results incl. tables

Table 1: Skin irritation scores of T-1063FM, after a single 4-hour dermal exposure

Animal no.	Hours after removal of the test material:
	1h	24h	48h	72h
	A-B	A-B	A-B	A-B
2	0-0	0-0	0-0	0-0
4	0-0	0-0	0-0	0-0
6	0-0	0-0	0-0	0-0

A=erythema (including ischemia, haemorrhages and incrustation); B = oedema       

 

Table 2: Mean values for erythema an oedema of each rabbit scored at 24, 28 and 72h after treatment with T-1063FM

Animal no.	Erythema	Oedema
2	0.0	0.0
4	0.0	0.0
6	0.0	0.0

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU