Phosphorous ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008

Reliability:

1 (reliable without restriction)

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

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:

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, 8 – 9 weeks old
- Weight at study initiation: 183 – 197 g
- Fasting period before study: The day before treatment the animals will be fasted. The food, but not water will be withheld overnight. Animals will be w eighed just before starting the treatment. The food will be given back 3 hours after the treatment.
- Housing: Group caging (3 animals/cage)
- Diet: Animals will receive 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, and tap water from municipal supply, as for human consumption from 500 ml bottle ad libitum.
- Water: The drinking water is routinely analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 °C
- Humidity (%): 32 - 56 %
- Air changes (per hr): 8-12 air exchanges/hour by central air-condition system.
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sunflower oil

Details on oral exposure:

VEHICLE
- Vehicle volume admistered: 10 mL/kg bw (was applied as a constant volume; the concentration was adjusted to ensure constant volumes as all dose levels)
- Lot/batch no. (if required): 2007.07.17

MAXIMUM DOSE VOLUME APPLIED:
200 mg/mL

DOSAGE PREPARATION:
Animals will be treated with the test item mixed in the vehicle prepared freshly on the day of treatment.

Doses:

300 mg/kg bw ; 2000 mg/kg bw

No. of animals per sex per dose:

12 female animals (nulliparous, non pregnant); 3 animals/dose level

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: animals were observed individually 15 and 30 minutes, 1h, 2h, 3h, 4h and 6h after the treatment and once each day 14 d ays thereafter.
- Weight assessment: The body weights were measured and recorded on day 0 (beginning of the experiment), on days 7 and 14 with a precision of 1g
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, pathology

Statistics:

NA

Results and discussion

Preliminary study:

NA

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Mortality:

GARDO TP10451 did not cause mortality at 300 mg/kg bw and 2000 mg/kg bw dose levels in female rats.

Clinical signs:

300 mg/kg bw – Treatment group 1 and Treatment group 2
No clinical signs were noted for these animals (3/3 Treatment group 1, 3/3 Treatment group 2). The behaviour and general state of animals were considered to be normal on the day of the treatment and during the remaining days of study.
2000 mg/kg bw – Treatment group 3 and Treatment group 4
There were no clinical signs on animals of these groups (3/3 in Treatment group 3 and 3/3 in Treatment group 4) on the day of the treatment and during the following 14-day observation period.

Body weight:

The body weight development of each animal treated with 300 mg/kg bw (Treatment groups 1 and 2) and 2000 mg/kg bw (Treatment groups 3 and 4) was normal during the two week observation period, similar to untreated female animals of the same age and strain.

Gross pathology:

NA

Other findings:

NA

Any other information on results incl. tables

Necropsy:

300 mg/kg bw – Treatment group 1 and Treatment group 2

Pinprick-sized haemorrhages (1/3 in group 1 and 2/3 in group 2) and pale raised areas (1/3 in group 2) were observed in the lungs.

2000 mg/kg bw – Treatment group 3 and Treatment group 4

In the lungs, pinprick-sized haemorrhages (2/3 in group 3 and 1/3 in group 4) and pale raised areas (2/3 in group 4) and in the uterus hydrometra (2/3 in group 3) were observed at the terminal necropsy of these animals.

In summary, no test item related macroscopic changes were found at the necropsy. The haemorrhages, and pale raised areas in the lungs, referred to circulatory insufficiency developed during the anaesthesia and exsanguination procedure, which are also observable in untreated animals after anaesthesia. Uterine hydrometra due to the sexual cycle is a common finding in experimental rats.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Under the conditions of the present study, a single oral administration of the test item Gardo TP10451 did not cause death of female CRL:(WI)BR rats at 300 mg/kg bw and 2000 mg/kg bw dose levels.

Executive summary:

Under the conditions of the present study, a single oral administration of the test item Gardo TP10451 did not cause death of female CRL:(WI)BR rats at 300 mg/kg bw and 2000 mg/kg bw dose levels.

According to the Globally Harmonised Classification System, the acute oral LD50 value of Gardo TP10451 was greater than 2000 mg/kg body weight in female CRL:(WI) BR rats and it was ranked into Category 5.

According to directive 2001/59/EC, classification of Gardo TP10451 by the oral route is not required based on the results of this study.