Registration Dossier

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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
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

Constituent 1
Chemical structure
Reference substance name:
tetrabenzyl diphosphate
EC Number:
628-817-3
Cas Number:
990-91-0
Molecular formula:
C28H28O7P2
IUPAC Name:
tetrabenzyl diphosphate
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:
no clinicals signs observed
Body weight:
Animals showed expected gains in bodyweight over the study period, except for one female which showed a bodyweight loss during the first week and expected gain in bodyweight during the second week.
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.