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

Endpoint summary

Description of key information

An oral toxicity study and a dermal toxicity study according to 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 were performed to test the acute toxicity of the substance.
The studies were guidelines conform and performed under GLP conditions.
Basing on the results of the studies, REGULATION (EC) No 1272/2008 on Classification, Labelling and Packaging of substance would indicate the following: 
Classification Acute oral toxicity: toxic Category 4 
Classification Acute dermal toxicity: Not required 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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)

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

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 25 - April 9, 1993

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Number and sex:
5 males + 5 female/group
Body weight:
Males: 225-250 g; Females: 200- 225 g
Age:
7 - 9 weeks
Acclimition:
5 days before the start of the test. Animals were observed daily to ascertain their fitness for the study.
Housing:
individual caging in air-conditioned rooms. Temperature: 22°C+/-2; Relative humidity: 55%+/-10; Air changes: about 20/hour filtered on HEPA 99.97%; Light: 12 hour cycle

Type of coverage:

occlusive

Details on dermal exposure:

Administration route: epidermal
Reason for selection of administration route: possible accidental exposure for humans
Administration frequency: single
Observation period: 14 days after the administration
Preparation of animals skin: approximately 24 hours before the test, for was clipped from the dorsal and ventral area of the trunk of the test animals. Care was taken to avoid abrading the skin which could alter its permeability. An area of about 6x5cm of the body dorsal surface was cleared for the application of the test article. This area corresponding to about 10% of the total body surface.
Administration of the test article: by uniform application onto the cleared area. The treated area was covered with a porous gauze deressing fixed to the skin with hypoallergenic non irritating tape. The test side was further covered in a suitable manner in order to ensure that the animals could not ingest the test substance. At the end of the exposure period the residual test substance was wiped off.

Duration of exposure:

24 hours

Doses:

one group of 5rat/sex administered a single dose of 2000 mg/kg (limit dose).

No. of animals per sex per dose:

5 males + 5 female/group

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the observation period.

Clinical signs:

other: No general clinical signs were noticed. Erythema and crusts of the skin were observed at the application site of some rats starting from day 2- 3 and lasting up to days 4 - 7 of the study.

Gross pathology:

Animals killed at the end of the observation period
No changes were observed in the animals killed at the end of the study.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The test article Addotto GM 102 E/BAF 1/1, when administered by dermal route to rat, under the conditions adopted in this experiment, did not cause mortality at the limit dose of 2000 mg/kg.
The LD50 by dermal route is higher than 2000 mg/kg.
Local reversible irritation changes were the only signs observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

In the oral toxicity study, the acute toxicity of the substance was investigated after a single oral administration (volume 10 ml/kg) to Sprague Dawley rats followed by a 14-day observation period. (Doses: 150, 307, 440 and 615 mg/kg .

The animals were sacrificed at the end of the observation period and subjected to necropsy examination. The results of the test indicate that the test item, has a LD50 of 423.1 mg/kg (DL50 between 300 and 2000 mg/kg).

In the dermal toxicity study, the acute toxicity the test substance was investigated following administration of a single dermal dose to the rat. No mortality occurred following dosing and no significant clinical signs were observed. These results indicate that the test item, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg b.w.. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.

Justification for selection of acute toxicity – oral endpoint
One study available.

Justification for selection of acute toxicity – dermal endpoint
One study available.

Justification for classification or non-classification

Basing on the results above reported,REGULATION (EC) No 1272/2008 (EURegulation onClassification, Labelling and Packaging of substances and mixtures) would indicate the following:

 

Oral Toxicity

Classification : Acute oral toxicity - Category 4

Signal word : Warning

Hazard statement (Oral) : H302: Harmful if swallowed

 

Dermal toxicity

Classification : Not required

Signal word : None indicated

Hazard statement : None indicated