Biphenyl-4,4'-diyl tetraphenyl bis(phosphate)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 28 - February 11, 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

of 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

of 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

of 1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4'-[(diphenoxyphosphoryl)oxy]-[1,1'-biphenyl]-4-yl diphenyl phosphate

EC Number:

700-627-6

Cas Number:

17270-01-8

Molecular formula:

C36H28O8P2

IUPAC Name:

4'-[(diphenoxyphosphoryl)oxy]-[1,1'-biphenyl]-4-yl diphenyl phosphate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Wistar rats, strain: Crl:WI (Han) (outbred, SPF-Quality), with appropriate range of bodyweight at study start.
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation (day of dosing): Approx. 12 weeks.
- Weight at study initiation( day of dosing): Mean (males): 337 g, minimum 324 g, maximum 349 g.
Mean (females): 211 g, minimum 207 g, maximum 217 g.
- Housing: Individual housing in M III type cages. (During acclimatization group housing in M IV type cages).
- Bedding material: Sterilized sawdust (Litalabo, S.P.P.S., Argenteuil, France).
- Cage enrichment: Paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, UK).
- Diet (ad libitum): Commercially available rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (ad libitum): Tap water
- Acclimation period: At least 5 days before treatment start under laboratory conditions.

Routine analysis of the sawdust, paper, diet and water, did not provide evidence of contamination that might have affected the study integrity.


ENVIRONMENTAL CONDITIONS

Animal housing and environmental conditions were appropriate for acute toxicity testing in the rat: Controlled environment with approximately 15 airchanges per hour, 12 hours artificial fluorescent light and 12 hours darkness per day, 19.0 - 20.5°C and 48 – 78% relative humidity. Due to a technical failure of the temperature and relative humidity sensors in the animal room in which in which the animals were housed, the temperature and relative humidity records were taken from another animal room connected to the same temperature and relative humidity regulation system and therefore considered to be representative for the present study.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

polyethylene glycol

Remarks:

400 (Merck, Darmstadt, Germany)

Details on dermal exposure:

TEST SITE
- Preparation: One day before exposure an area of approximately 5x7 cm on the back of the animal was clipped. During health inspection of the animals prior to commencement of treatment, special attention was paid to the skin to be treated, which was intact and fre e from any abnormality.
- Area of treated skin: Ca. 25 cm2 in males, ca.. 18 cm2 in females corresponding to ca. 10% of total body surface.
- Type of wrap used: Surgical gauze patch (Surgy 1 D), successively covered with aluminium foil and Coban elastic bandage. For females additional
fixation of the bandage with Micropore tape.

REMOVAL OF TEST SUBSTANCE
Occlusive treatment of the clipped, intact skin lasted 24 hours. Then the dressings (gauze, foil, bandages, tape) were removed and residual test substance washed off the skin with tap-water.

TEST MATERIAL AND DOSE PREPARATION
- Administered Dose of test substance: 2000 mg/kg bw
- Administration Volume: 10 mL per kg body weight (specific gravity of the vehicle of 1.125 was accounted for)

The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.

- Justification for choice of vehicle:
Trial formulations at the testing laboratory and test substance data supplied by the sponsor led to the choice of this vehicle.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Duration of the observation period following administration start (day 1) was 14 days during which mortality/survival and clinical signs were recorded at: 0, 2 and 4 hours after administration start on day 1 and twice daily (mortality/survival) or once daily (clinical signs) thereafter until day 15. Body weight was recorded on days 1 (prior to administration), 8 and 15 for each animal. On day 15, all animals were necropsied and macroscopic pathology findings recorded.

Statistics:

Statistical analysis is inappropriate for this study, as there was only one dose group.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths at the limit dose of 2000 mg/kg.

Mortality:

There were no premature deaths.

Clinical signs:

other: Clinical signs were confined to Day 2, comprising of: - hunched posture in all animals (Nos. 1 to 10) - piloerection in two male animals (Nos. 1 and 4) and - chromodacryorrhoea (snout), slight in degree, in one male animal (No. 1).

Gross pathology:

Necropsy of each animal did not reveal any macroscopic pathology findings.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In view of the dermal LD50 > 2000 mg/kg bodyweight attained in the present study, its outcome does not necessitate any classification or labelling regarding acute dermal toxicity according to EU regulations (DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008).