Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-1,3-propanediyl] P,P,P',P'-tetrakis(2-chloro-1-methylethyl) ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 - 30 November 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

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 (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2,2-bis(chloromethyl)trimethylene bis(bis(2-chloroethyl)phosphate)

EC Number:

253-760-2

EC Name:

2,2-bis(chloromethyl)trimethylene bis(bis(2-chloroethyl)phosphate)

Cas Number:

38051-10-4

Molecular formula:

C13H24Cl6O8P2

IUPAC Name:

2,2-bis(chloromethyl)propane-1,3-diyl tetrakis(2-chloroethyl) bis(phosphate)

Details on test material:

Product name: Amgard V6
Appearance: very pale straw coloured viscous 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, UK
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.19 - 2.54 kg
- Housing: individually, suspended metal cages
- Diet: ad libitum (STANRAB SQC Rabbit Diet)
- Water: ad libitum
- Acclimation period:minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 20
- Humidity (%): 49 - 56
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL test material, under a 2.5 x 2.5 cm gauze patch

Duration of treatment / exposure:

4 hours

Observation period:

1 hour, 24, 48 and 72 hours after removal of patches
Additional observation at Day 7 to assess reversibility

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap: adhesive tape (BLENDERM) plus elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing: cotton wool soaked in diethylether
- Time after start of exposure: 4 hours

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

1.2

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Desquamation observed after 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: desquamation observed after 7 d

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

- 1 hour: very slight erythema was noted at two treated skin sites and well-defined erythema at on skin site
- 24, 48 hours: very slight erythema persisted at all treated skin sites
- 72 hours: very slight erythema at one site, the other two skin sites appeared normal
- 7 days: desquamation at two treated skin sites, the other appeared normal

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Whilst there is some transient irritation according to Draize criteria, it is not sufficient to classify as irritant according to the EU criteria. The Classification is 'not irritating'.

Executive summary:

In a primary dermal irritation study, conducted according to OECD Guideline No.404, the shaved skin of 3 New Zealand white rabbits (females) was exposed to 0.5 ml of undiluted 2,2-bis(chloromethyl)trimethylene bis(bis(2-chloroethyl)phosphate) for 4 hours under semiocclusive conditions. The animals then were observed for up to 7 days. Irritation was scored by the method of Draize. In this study the substance was slightly irritant to rabbit skin, but the level of irritation was not suifficient for a classification as skin irritant according to EU criteria.