Phosphorous ester

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-04-09 to 2009-04-23

Reliability:

1 (reliable without restriction)

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

esterification products of castor oil and polyphosphoric acids

EC Number:

614-406-6

Cas Number:

68308-61-2

Molecular formula:

C57H107P3O18

IUPAC Name:

esterification products of castor oil and polyphosphoric acids

Details on test material:

- Name of test material (as cited in study report): GARDO TP10451
- Physical state: liquid
- Analytical purity: 100%
- Lot/batch No.: 2939R
- Expiration date of the lot/batch: 2010-02-18

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (Europe) Laboratories Inc. TOXI COOP Ltd. 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: Young adult rats
- Weight at study initiation: Male: 246 - 283 g; Female: 201 – 216 g
- Fasting period before study:
- Cage type: Type II polypropylene/polycarbonate
- Diet: ssniff® SM R/M-Z+H "Autoclavable complete feed for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany
- Water: tap water from the municipal supply



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 – 24°C
- Humidity (%): 35-52 %
- Air changes (per hr): 8-12 air exchanges/hour by central air-condition system.
- Photoperiod (hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
-The test item was applied as a single dose uniformly over an area of approximately 10 per cent of the total body surface


REMOVAL OF TEST SUBSTANCE
- Washing: residual test item was removed using water at body temperature
- Time after start of exposure: 24 h


TEST MATERIAL
-The test item was administered in a single dose of 2000 mg/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 male and 5 female with a single dose level of 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful individual clinical examination was made on the day of treatment 1 h and 5 h after the administration of the test item, and once each day for 14 days thereafter. The body weight of each animal was recorded on day 0 (beginning of the experiment), on day 7 and on day 14 with a precision of 1 g.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy

Statistics:

NA

Results and discussion

Preliminary study:

NA

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There was no mortality.

Clinical signs:

Ther were no clinical signs.

Body weight:

The mean body weight and the body weight gain of the male and female animals were considered to be normal during the two-week observation period, similar to the expected values in untreated animals of the same age and strain.

Gross pathology:

No macroscopic alterations due to the effects of the test item were found. Gross necropsy revealed pinprick-sized haemorrhages (2/5 male, 1/5 female) and pale raised areas (1/5 male) in the lungs due to the method of anaesthesia and exsanguinations, which are also observable in untreated animals after anaesthesia. Unilateral pyelectasia (1/5 male) as individual alteration is a common finding also found in untreated rats. Hydrometra (2/5) related to the female sexual cycle, is a frequent observation in experimental rats, which had no toxicological significance.

Other findings:

NA

Any other information on results incl. tables

no remarks

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

LD50 value of Gardo TP10451 was greater than 2000 mg/kg bw in male and female.

Executive summary:

Under the conditions of the present study, single 24-hour dermal administration of the test item Gardo TP10451 induced erythema, oedema and scars on the treated skin. Mortalities were not observed, neither in male nor in female CRL:(WI)BR rats. The acute dermal LD50 value of Gardo TP10451 was greater than 2000 mg/kg bw in male and female CRL: (WI) BR rats. According to the current status of the Globally Harmonised Classification System 1), 2) the test item was ranked into Category 5 (or unclassified) and the LD50 was greater than 2000 mg/kg bw, with a cut-off value of 5000 mg/kg bw (or unclassified) in female CRL:(WI) BR rats. Gardo TP10451 does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances.