Bis(2,4,4-trimethylpentyl)phosphinic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 29th to November 11th, 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

GLP guideline study with some restrictions: no certificate of analysis and no data on the animal environmental conditions, occlusive dressing, abrasion of skin prior to application of test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

: no certificate of analysis and no data on the animal environmental conditions (temperature, humidity, air change), occlusive dressing, abrasion of skin prior to application of test substance.

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2,4,4-trimethylpentyl)phosphinic acid

EC Number:

280-445-7

EC Name:

Bis(2,4,4-trimethylpentyl)phosphinic acid

Cas Number:

83411-71-6

Molecular formula:

C16H35O2P

IUPAC Name:

bis(2,4,4-trimethylpentyl)phosphinic acid

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Willow Pond Rabbitry, Montpelier, Indiana, USA
- Age at study initiation: no data
- Weight at study initiation: from 2.20 to 2.48 kg
- Fasting period before study: no
- Housing: individually housed in wire-bottomed cages suspended above the droppings.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow 5322, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: yes for 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: To: no data

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back of rabbit
- % coverage: 10 % of the total body surface (approximately 240 cm²)
- Type of wrap if used: layer of 4-ply gauze and two single layers tock. The trunk of the rabbit was then wrapped with rubber latex dental dam and the dental dam taped at the edges with 1 inch micropore tape to form an airtight occlusive wrap.
- The skin of rabbits was abraded prior to treatment by making a series of parallel, epidermal abrasions, every 2 or 3 centimeters longitudinally with a 25 -gauze hypodermic needle. These abrasions were made sufficiently deep to penetrate the stratum cornuem but not to disturb the derma or to produce bleeding.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residual test material was wiped off
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.94 ml/kg
- Concentration (if solution): not applicable, the substance is applied as supplied (pure substance)
- Constant volume or concentration used: not applicable, only one dose level was tested
- For solids, paste formed: not applicable

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations of the animals at least twice daily, weighing at day -1; 0; 2; 3; 6; 10 and 13
- Necropsy of survivors performed: yes: on the visceral and thoracic cavities
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

if mortality occured, the LD50 would be calculated according to the Lichtfield and Wilcoxon method.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no death occured

Clinical signs:

other: no animals exhibited signs of systemic toxicity. The evaluation of local skin reactions revealed mild to slight erythema in all animals over total surface area to scattered patches, day 1 through 13, and mild to slight edema in 9/10 animals over total sur

Gross pathology:

The examination of the visceral and thoracic cavities of the test animals revealed a congestion of illeum in one male. There were no significant gross pathologic findings in all other animals.

Other findings:

no other findings

Applicant's summary and conclusion

Interpretation of results:

other: not classified as harmful or toxic according to the CLP Regulation (EC) No.1272/2008

Conclusions:

LD50 (rabbit, male/female)> 2000 mg/kg bw

Executive summary:

In a limit acute dermal toxicity study performed similarly to the OECD test guideline No. 402 and in compliance with GLP, young adult albino New Zealand rabbits (5/sex) were dermally exposed to undiluted test material at the dose level of 2000 mg/kg bw. Prior to treatment, the skin of all animals was abraded (worst case approach). The treated area of dorsum (10 %) was covered by an occlusive dressing for 24 hours. Twenty-four hours after the start of exposure, the dressing was removed, the remained test material was wiped off and the animals were then observed for 14 days.

No animal died during the study and no animals exhibited signs of systemic toxicity. However, the evaluation of local skin reactions revealed mild to slight erythema in all animals over total surface area to scattered patches, day 1 through 13, and mild to slight edema in 9/10 animals over total surface to 1/4 surface area days 1 through 13. Furthermore, slight to moderate atonia, moderate to slight cracking, slight scaling, exfoliation, and dark and blue areas were observed on skin animals after the removal of the dressing and through several days following this removal. Those skin effects are in favour of a skin irritant potential of the substance. However the experimental conditions (abraded skin, exposure for 24hrs under occlusive patch) are too drastic to determine the skin irritation classification according to the current criteria for classification available in the Regulation (EC) 1272/2008 (CLP).ù

LD50 (rabbit, male/female)> 2000 mg/kg bw