Tetrakis(hydroxymethyl)phosphonium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 12 january 1989 to 15 mar 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetrakis(hydroxymethyl)phosphonium chloride

EC Number:

204-707-7

EC Name:

Tetrakis(hydroxymethyl)phosphonium chloride

Cas Number:

124-64-1

Molecular formula:

C4H12O4P.Cl

IUPAC Name:

tetrakis(hydroxymethyl)phosphonium chloride

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France.
- Age at study initiation: 7 to 10 weeks of age
- Weight at study initiation: 200 to 248 g
- Fasting period before study: no data
- Housing: individually in metal cage with wire mesh floors.
- Diet: standard laboratory rodent diet (Labsure LAD 1), ad libitum
- Water: domestic potable water, ad libitum
- Acclimation period: 22 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 47
- Air changes (per hr): 15
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From 13 january 1989 to 27 january 1989

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region (appoximately 50 x 50 mm)
- % coverage: 10
- Type of wrap if used: treated area was covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated area of skin decontaminated by washing in warm (30-40°C) water and blotting dry with absorbent paper
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 15.1 ml/kg (specific gravity 1.325)
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw based on test material
1600 mg/kg bw based on active ingredient

No. of animals per sex per dose:

10 animals (5/sex/dose)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of 5 hours). On subsequent days the animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on weekdays and 11.30 hours on public holidays, including saturday and sunday.
- Individual bodyweights of rats were recorded on days 1 (day of dosing), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 600 mg/kg bw

Based on:

act. ingr.

Mortality:

There were no deaths following a single dermal dose of THPC at 2000 mg/kg bw.

Clinical signs:

other: There were no signs of systemic reaction to treatment.

Gross pathology:

Terminal necropsy findings were normal.

Other findings:

- Other observations: dermal responses
Slight erythema only was observed in all males after removal of the dressings. This had resolved by day 3 of the study. Slight erythema only was observed in four of the males on day 5 of the study and small scabs on day 6 of the study. The scabs has healed by day 9 of the study. A small white area was observed in the remaining male on day 5 and a scab had formed by day 9, this persisted until the end of the study (day 15).

Well-defined dermal irritation was observed in all five females after removal of the dressings. Irritation reactions had resolved by day 6. Hardening of the skin made assessment of oedema impossible in three of the animals. Large or small white areas were observed in four of the animals, scab forming by days 7, 9 or 14. The scabs persisted until the end of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this test, the acute lethal dermal dose (LD50) to rats of THPC was found to be greater than 2000 mg/kg bw based on test material (or > 1600 mg/kg bw based on active ingredient).

Executive summary:

In an acute dermal toxicity study (Ligett and Allan, 1989), groups of 10 Sprague-Dawley rats (males / females) were dermally exposed to THPC ( Tetrakis (hydroxymethyl) phosphonium chloride) for 24 hours to 10 % of body surface area at 2000 mg/kg bw. Animals then were observed for 14 days.

No deaths occured following a single dermal dose of THPC at 2000 mg/kg bw (limit test). No signs of systemic reaction to treatment were observed. A loss in bodyweight gain was recorded for one female on Day 8. All other rats achieved anticipated bodyweight gains throughout the study.

Slight erythema to well-defined dermal irritation was observed in all animals after the dressings. Terminal necropsy findings were normal. The acute lethal dermal dose to rats of THPC (80%) was found to be greater than 2000 mg/kg bw (or > 1600 mg/kg bw based on active ingredient).

This study is classified as acceptable and satifies the requirement for Test Guideline OECD 402 for acute dermal toxicity data.