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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 1994/11/10 and 1994/11/24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according a recognised guideline and under GLP condition.

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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes (incl. QA statement)

Remarks:

1994-03-16

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

other: liquid stored at room temperature

Details on test material:

- Physical state: pale straw-coloured liquid
- Storage condition of test material: room temperature
- Stability under test conditions: no data
- Other: container: white plastic tub

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 (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 10 - 14 weeks
- Weight at study initiation: males: 228 - 259 grams; females: 213 - 225 grams
- Fasting period before study: no data
- Housing: Individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22 °C
- Humidity (%): 48 - 55%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: no data

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approx. 5 cm x 4 cm (back and flanks of each animal)
- % coverage: approx. 10%
- Type of wrap if used: surgical gauze semi occluded with a piece of self-adhesive bandage (hypertie)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): exposure area was wiped with cotton whool moistened with destilled water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.54 ml/kg
- Concentration (if solution): 2000 mg/kg
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg BW

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to application of the test material on Day 0, Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology.

Statistics:

Not required (limit test)

Results and discussion

Preliminary study:

No data

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:

> 1 306 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality was observed

Clinical signs:

other: - No signs of systemic toxicity were noted during the study. - Yellow-staining of the fur was noted from day 1-8 after dosing in all animals.

Gross pathology:

No abnormalities were noted at the necropsy

Other findings:

Other:
Skin irritation:
- very slight to well-defined erythema with desquamation (males and females)
- occasional signs of crust formation and an isolated incident of hardened light-brown coloured scab or small superficial scattered scabs (females).
All affected animals recouvered before the end of the 14-day observation period.

Any other information on results incl. tables

Table 7.2.3/2: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

Dose (mg test material/kg bw)	Mortality (# dead/total)			Time range of deaths (hours)	Number with evident toxicity(#/total)
	Male	Female	Combined		Male	Female	Combined
2000	0	0	0	-	0	0	0

 

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal lethal dose (LD50) of the THPC-urea, in the Sprague-Dawley strain rat was found to be greater than 1306 mg AI/kg bw. Based on the facts that neither mortality neither systemic effects were observed at the higest tested dose of 1306 mg AI/kg bw, THPC-urea should not be classified by dermal route; according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC)

Executive summary:

A limit test for determination of the acute dermal toxicity in the rat is performed according to OECD guideline 402 and EU Directive 92/69/EEC method B3.10. Sprague Dawley rats (5 males/5 females) were exposed to water solution of Tetrakis (hydroxymethyl) phosphonium chloride, oligomeric reaction products with urea (THPC-urea) at the limit dose of 2000 mg test material/kg (equivalent to 1306 mg AI/kg bw) for 24 hours. Animals then were observed for 14 days. Examinations for mortality, clinicals signs and body weight gain were performed during the 14 -day observation period for all animals. All animals were necropsied at the end of the observation period.

No mortality was observed during the study. Yellow-staining of the fur was noted from day 1-8 after dosing in all animals. Common signs of skin irritation noted were very slight to well-defined erythema with desquamation, occasional signs of crust formation and isolated incident of hardened light-brown colored scab or small superficial scattered scabs (females). All affected animals recovered before the end of the 14-day observation period. All animals showed expected gain in body weight during the study, except for 2 females which showed body weight loss during the first week of the study. At necropsy, no significant findings were reported.

The acute dermal lethal dose (LD50) of the THPC-urea, in the Sprague-Dawley strain rat was found to be greater than 1306 mg AI/kg bw. Based on the facts that neither mortality nor systemic effects were observed at the higest tested dose of 1306 mg AI/kg bw, THPC-urea should not be classified by dermal route; according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC)