Tetrakis(hydroxymethyl)phosphonium chloride, oligomeric reaction products with urea

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 3/11/1994 and 17/11/1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in full compliance with OECD guideline. Exposure duration higher than 4h (at day-7, traces of remaining product found on the fur of all rabbits).

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:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Products found on the fur at day 7

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Products found on the fur at day 7

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

1994-03-16

Test material

Test material information

Constituent 1

Test material form:

other: liquid stored at room temperature

Details on test material:

- Physical state: liquid (pale straw-coloured liquid)
- Storage condition of test material: room temperature

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, Sandbach, Cheshire, UK

-Age at study initiation : 12 to 16 weeks

-Weight at study initiation: 2.31 to 2.59 kg

-Housing: individually

-Diet: ad libitum

-Water: ad libitum

-Acclimation period: Minimum 5 days

ENVIRONMENTAL CONDITIONS

Temperature: 16 – 19°C
Humidity: 56 -65%
Air exchange rate: 15 per hour
Photoperiod: 12 hours light, 12 hours dark

IN-LIFE DATES: No data

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

VEHICLE: none

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

6 (4 male, 2 female)

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm (approximately 6 square cm)
- % coverage: no data
- Type of wrap: gauze patch held in place with elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated site was removed by gently swabbing with cotton wool soaked with 74% industrial methylated spirits.
- Time after start of exposure: 4 hours

SCORING SYSTEM: The treated area was scored for erythema and oedema using a numerical system based on that described by Draize et al. (1959) and the primary dermal irritation index (PDII) was calculated.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: over 24 to 72 hours

Score:

ca. 2.2

Max. score:

4

Reversibility:

not fully reversible within: 14 days for 2 animals

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: over 24 to 72 hours

Score:

ca. 1.7

Max. score:

4

Reversibility:

not fully reversible within: 7 days for 2 animals

Results 3

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: over 24 to 72 hours

Score:

3.3

Irritant / corrosive response data:

See Table 7.3.1/1
2/6 animals showed corrosive effects (see Others efffects for more details)

Other effects:

Well-defined erythema was noted at two treated skin sites one hour after patch removal. Small areas of green-coloured dermal necrosis were noted at these two treated skin sites at the 24, 48 and 72-hour observations. Slight oedema was noted at these two treated skin sites one hour after patch removal with slight to moderate oedema at the 24-hour observation and slight oedema at the 48 and 72-hour observations. Skin reactions prevented accurate evaluation of erythema and oedema at these two treated skin sites at the 7-day observation and at one site at the 14-day observation. Well-defined erythema surrounding other skin reactions was noted at these two treated skin sites at the 24, 48, 72-hour and 7-day observations. Small superficial scattered scabs were noted at these two treated skin sites at the 14-day observation. Scar tissue was noted at both sites at the 14-day observation. Glossy skin and reduced re-growth of fur were also noted at one treated skin site at the 14-day observation.

Very slight erythema was noted at four treated skin sites one hour after patch removal, with very slight to well-defined erythema at the 24, 48 and 72 hour observations. Very slight oedema was noted at four treated skin sites one hour after patch removal with very slight to slight oedema at the 24-hour observation. Very slight oedema was noted at two treated skin sites at the 48-hour observation and at one treated site at the 72-hour observation. Crust formation or desquamation was noted at four treated skin sites at the 7-day observation. Desquamation was noted at one treated skin site at the 14-day observation.

Any other information on results incl. tables

Table 7.3.1/1: Irritation data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility Erythema/Eschar Formation Edema Max. score: 4 Max. score: 4 24 h 1/1/2/4/4/2 1/1/2/3/2/1 48 h 1/1/2/4/4/1 0/0/1/2/2/1 72 h 1/1/2/4/4/1 0/0/1/2/2/0 Average 24h, 48h, 72h 2.3 -2.2 -2.2 1.7 -1 -0.8 Reversibility* nc nc Average time (unit) for reversion - -

Reversibility*: nc: not completely reversible

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, Tetrakis (hydroxymethyl) phosphonium chloride, oligomeric reactions with urea (THPC-urea) is classified in
Category 1C, H314 according to the CLP regulation (1272/2008) and as corrosive (C, R34) according th the Directive 67/548/EEC.

Executive summary:

In a primary dermal irritation study, young adult New Zealand White rabbits (4 males and 2 females) were dermally exposed to 0.5 mL of a water solution of Tetrakis (hydroxymethyl) phosphonium chloride, oligomeric reactions with urea (THPC-urea). Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 14 days. The skin reactions were assessedat 1,24, 48 and 72 hours, as well as 7, 10 and 14 days after removal of the dressing.The mean score was calculated across 3 scoring times; 24, 48 and 72 hours after patch removal, for each animal separately. It should be noted that on day-7 remaining traces of test material were observed on all animals; therefore, it was considered that exposure duration was higher than 4-h.

The mean score calculated for 24 -48 and 72 hours was 2.2 for erythema/ eschar and 1.7 for oedema. At the 14 -day observation, scar tissue and small superficial scattered scabs were noted in one female (the mean erythema score (24, 48 and 72 hours): 4 and the mean oedema score (24, 48 and 72 hours): 2) and scar tissue reduced re-growth of fur, glossy skin and small superficial scattered scabs were observed in one male (the mean erythema score (24, 48 and 72 hours): 4 and the mean oedema score (24, 48 and 72 hours): 2.3).

Given these results,Tetrakis (hydroxymethyl) phosphonium chloride, oligomeric reactions with urea (THPC-urea) is classified in Category1C, H314 (causes severe skin burns and eye damage) according to the CLP regulation (1272/2008) and as corrosive (C, R34) according to the Directive 67/548/EEC.