Phenyl phosphorodichloridate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

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

GLP compliance:

yes (incl. QA statement)

Remarks:

1996-02-22

Test material

Test material information

Constituent 1

Reference substance name:

Phenyl phosphorodichloridate

EC Number:

212-220-6

EC Name:

Phenyl phosphorodichloridate

Cas Number:

770-12-7

Molecular formula:

C6H5Cl2O2P

IUPAC Name:

phenyl dichlorophosphate

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: David Percival Ltd, Moston, Sand bach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.32 to 2.79 kg
- Housing: individually housed in suspended metal cages
- Diet: free access to STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Water: free access to water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17°C to 21°C
- Humidity (%): 46% to 65 %
- Air changes (per hr): 15 changes
- Photoperiod (hrs dark / hrs light): 12h/12h

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5mL

Duration of treatment / exposure:

3 minutes and 1h

Observation period:

24h, 48, 72h, day 7 and day 14

Number of animals:

3

Details on study design:

On the day before the test each rabbit was clipped free of fur from the dorsal flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

One rabbit was initially treated. Three suitable test sites were selected on the back of the rabbit. At each test site a quantity of 0.5 ml of the test material, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. Each patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animal was returned to its cage for the duration of the exposure period.

One patch was removed at each of three time points: 3 minutes and 1 hour after application. Due to adverse reactions the third patch was also removed after one hour. Any residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.

After consideration of the skin reactions produced in the first animal, two additional animals were treated with 0.5 ml of test material. One patch was applied to the back of each rabbit, and was allowed to remain in contact with the skin for a period of three minutes.

Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H, (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: corrosive

Results 2

Irritation parameter:

edema score

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: corrosive

Any other information on results incl. tables

Individual skin reactions following 1-hour exposure period

Skin reation	Observation time	Female N° 69 (2.32 kg) Score /observation
Erythema / Eschar formation	1 hour	4 / green-coloured dermal necrosis covering whole of treatment site
	24 hours	4 / green-coloured dermal necrosis covering whole of treatment site
	48 hours	4 / green-coloured dermal necrosis covering whole of treatment site. Well-defined erythema surrounding other reaction
	72 hours	4 / green-coloured dermal necrosis covering whole of treatment site. Well-defined erythema surrounding other reaction. Blanching of the skin
	7 days	4 / green-coloured dermal necrosis covering whole of treatment site. Well-defined erythema surrounding other reaction. Blanching of the skin
	14 days	Adverse reactions prevent accurate evaluation of erythema. Ulceration. Animal killed due to ulceration in accordance with company policy
Oedema formation	1 hour	4
	24 hours	3
	48 hours	3/ oedema extends ventrally below treatment site
	72 hours	3
	7 days	3
	14 days	Adverse reactions prevent accurate evaluation of oedema

 

Individual skin reactions following 3-minute exposure period

Skin reation	Observation time	Individual scores
		Female N° 69 (2.32 kg)	Female N° 581 (2.79 kg)	Female N° 160 (2.64 kg)
Erythema / Eschar formation	1 hour	2	1	1
	24 hours	2	2	2
	48 hours	2	2	2
	72 hours	2	1	2
	7 days	1 (crust formation)	0 (slight desquamation)	1 (crust formation)
	14 days	0 (slight desquamation)	0	0 (moderate desquamation)
Oedema formation	1 hour	1	1	1
	24 hours	1	1	1
	48 hours	1	1	1
	72 hours	1	0	1
	7 days	1	0	0
	14 days	0	0	0

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

The phenyl dichlorophosphine is classified as corrosive to rabbit skin.

Executive summary:

Dermal toxicity of Phenyldichlorophosphate has been determined according to EU B.4 method and OECD test guideline 404 in compliance with GLP. Phenyldichlorophosphate was determined to be corrosive category 1B to the skin.