Diphosphoric acid, P,P,P',P'-tetrakis(phenylmethyl) ester

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From July 2004 to 2004-09-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

No certificate of analysis in the study report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

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

GLP compliance:

yes (incl. QA statement)

Remarks:

2003-02-13

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

dibenzyl {[bis(benzyloxy)phosphoryl]oxy}phosphonate

EC Number:

628-817-3

Cas Number:

990-91-0

Molecular formula:

C28H28O7P2

IUPAC Name:

dibenzyl {[bis(benzyloxy)phosphoryl]oxy}phosphonate

Test material form:

solid: particulate/powder

Details on test material:

CAS 990-91-0

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
- Females nulliparous and non-pregnant
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: At least 200 g (The weight variation did not exceed :!: 20% of the mean weight for each sex)
- Housing: suspended solid-tloor polypropylene cages fumished with woodflakes. The animais were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study
- Diet (e.g. ad libitum) & Water (e.g. ad libitum): Free access to mains drinking water and food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK) was allowed throughout the study.
- Acclimation period: acclimatisation period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): ifleen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous Light (06:00 to 18:00) and twelve hours darkness.

IN-LIFE DATES: From 16 August 2004 to 30 August 2004

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed ovcr the treatment area and senù-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin and surrounding hair wiped wi1h cotton wool mois1ened with distilled water to remove any residual test material.
- Time after start of exposure: 24-hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg

VEHICLE
- Amount(s) applied (volume or weight with unit): the test material was moistened with distilled water

Duration of exposure:

24 hours

Doses:

2000 mg/kg

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: 30 minutes, 1h, 2h and 4 hours after dosing and subsequently once daily for fourteen days.
- weighing:Days 0, 7 and 14
- Necropsy of survivors performed: yes
- Dermal reactions: primary irritation and scored according to scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" ln: Principles and Procedures for Evaluating the Toxicity ofHousebold Substances, National Academy of Sciences, Washington DC p.31

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortaliy observed

Clinical signs:

other: no clinicals signs observed

Gross pathology:

No abnomalities were noted at necropsy

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

Assessment of acute dermal toxicity with Tetrabenzyl pyrophosphate in the rat was realised according to the OECD 402 guideline and under GLP conditions.

Tetrabenzyl pyrophosphate was administered to 5 males and 5 females Sprague Dawley rats at 2000 mg/kg body weight.

Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice.

At 2000 mg/kg, no mortality occurred and no signs of dermal irritation were observed.