benzyl(diethylamino)diphenylphosphonium 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxyphenyl)propan-2-yl]phenolate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 10 to June 5, 1990

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD GLP in the testing of chemicals [C(81)30 final], regulation enforced by the Italian Health Authority (D.M. dated June 26, 1986 as published in G.U. no.198, August 27, 1986 and D.M.dated April 28, 1988 as published in G.U. no.107, May 9, 1988.

Principles of method if other than guideline:

The test method was in accordance with European Economic Community Guidelines-VI Amendment, Annex V, Directive 84/449/EEC.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

479-100-5

EC Name:

-

Cas Number:

577705-90-9

Molecular formula:

C38H36F6O2NP

IUPAC Name:

benzyl(diethylamino)diphenylphosphanium 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxyphenyl)propan-2-yl]benzen-1-olate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Addotto GM 102 E/BAF 1/1
- description: white powder
- batch: 14334/56
- stability: indefinitely stable
- storage conditions: at room temperature

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 Italia SpA, Calco (Como)
- Age at study initiation: about 7-9 weeks
- Weight at study initiation: males 217-250 g, females 169-225 g
- Housing: 5 animals/sex/cage in air-conditioned rooms
- Diet (e.g. ad libitum): pelleted diet ad libitum
- Water (e.g. ad libitum): from the municipal water main system
- Acclimation period: about one week before the start of the test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%):22% +/- 10
- Air changes (per hr): about 20/hr filtered on HEPA 99.97%
- Photoperiod (hrs dark / hrs light): 12 hr cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: arabic gum 5% water solution

Details on oral exposure:

Single administration
14 days of post-treatment period.

Doses:

150, 307, 440, 615 mg/kg
Administration volume 10 ml/kg

No. of animals per sex per dose:

5

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

423.1 mg/kg bw

95% CL:

365.7 - 489.6

Mortality:

No death occurred at the lowest dosage level (150 mg/kg) while mortality was observed at the three higher dosages.
Mortality was recorded between 30 mins and 2 days after administration.

Clinical signs:

other: No clinical signs or behavioral alterations were observed in animals trated at the lowest dosage level. At the higher dosages hypoactivity or sedation, ahallow breathin, piloerection, hunched posture and diarrhea were mainly observed. These signs appeared

Gross pathology:

On animals treated at the two higher dosage levels the main organs involved were lungs, stomach and small intestine.
Some animals belonging to the above dosage groups showed congestion and edema of lungs; one female rat treated at 440 mg/kg only showed pulmunary congestion.
Changes in the gastric mucosa were found to be induced by the test article administration in all the necropsied rats.
They consisted of congestion and corrosion for almost all the animals; two female rats treated at 440 mg/kg only showed congestive changes.
Test article in the stomach and catarrhal content in the small intestine were observed in all the animals. The only animal treated at 307 mg/kg, which died, was found cannibalized and one rat treated at 615 mg/kg had severe autolisis.

The autoptic examination performed on rats killed at the end of the observation period showed congestion of the glandular mucosa of the stomach in two animals treated at 150 mg/kg and in two animals treated at 307 mg/kg.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test article when administered by the oral route to rats under the experimental condition applied in this study was 423.1 mg/kg with 95% confience limits of 365.7 and 489.6 mg/kg.
At necropsy compound related changes were mainly found in the gastroenteric tract.

Executive summary:

Sprague Dawlwy Crl:CD rats (5 males and 5 females/group) received a single oral administration of Addotto GM 102 E/BAF 1/1 at the dosages of 150, 307, 440 and 615 mg/kg.

The test article was suspended in arabic gum 5% water solution and administered to rats at the constant volume of 10 ml/kg.

All rats were treated after a 16 hrs fasting period.

No deaths occurred at the lowest dosage level of 150 mg/kg while mortality was observed with a dose relationship (from 30 mins up to 2 day) at the dosages of 307 mg/kg (1F), 440 mg/kg (3M + 3F) and 615 mg/kg (5M + 4F).Animals treated at 150 mg/kg did not show clinicla signs or behavioral alterations. The main clinical signs observed at the three higher dosage levels were hypoactivity or sedation, shallow breathing, ploerection, hunched posture and diarrhea. These signs started within 30 mins - 3 hrs after administration and had different durations, ranging from days 2 -3 up to days 5 -6. During the day of dosing, salivation and palpebral closure were oberved in rats treated at 440 and 615 mg/kg and reddish nasal discharge was only observed in one 440 mg/kg dosed animal (beginning 3 hrs after the administration and continuing up to day 2).

Almost all the animals achieved recovery in 7 days.

The body weight gain was considered within normal limits.

Respiratory tract modifications (congestion and/or edema of lungs) were observed in some of the animals which died, while changes in the gastroenteric tract were observed in all dead animals. The gastroenteric changes were deemed test article-related.

The autopsy performed at the end of the observation period showed congestive changes of the glandular mucosa of the stomach in two animals treated at 150 mg/kg and in two animals treated at 307 mg/kg.

In conclusion the LD50 of the test article when administered by the oral route to rats under the experimental condition applied in this study was 423.1 mg/kg with 95% confience limits of 365.7 and 489.6 mg/kg.

At necropsy compound related changes were mainly found in the gastroenteric tract.