Diphenyl[4-(phenylsulfanyl)phenyl] sulfonium hexafluoroantimonate(1-)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 August 2008 - 27 August 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline 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 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

not specified

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diphenyl[4-(phenylsulfanyl)phenyl] sulfonium hexafluoroantimonate(1-)

EC Number:

680-227-5

Cas Number:

71449-78-0

Molecular formula:

C24H19F6S2Sb

IUPAC Name:

Diphenyl[4-(phenylsulfanyl)phenyl] sulfonium hexafluoroantimonate(1-)

Test material form:

solid: particulate/powder

Details on test material:

- Storage condition of test material: Room temperature in the dark.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CDtm

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Limited, Bicester, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: body weight variation did not exceed ±20% of the mean body weight at the start of treatment
- Fasting period before study: yes 24hrs before dosing and 3 -4 hours after dosing
- Housing: housed in groups of up to 4 individuals in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): free access to food (certified rat and mouse diet)
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): minimum of 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 : 12

IN-LIFE DATES: From: Not specified

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: DMSO
- Amount of vehicle (if gavage): not specified
- Justification for choice of vehicle:The test item did not dissolve /suspend in distilled water or arches oil BP
- Lot/batch no. (if required): not specified
- Purity: not stated

MAXIMUM DOSE VOLUME APPLIED: 10.0 mL/kg

DOSAGE PREPARATION (if unusual): the test item was dissolved in DMSO at concentration of 200 mg/ml and dose volume of 10 ml/kg.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: maximum guideline required concentration - 2000 mg/kg

Doses:

2000 & 300 mg/kg

No. of animals per sex per dose:

1 for 2000 mg/kg, 5 for 300 mg/kg

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2 and 4 hours after dosing then daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight on day 0, 7 and 14

Statistics:

Not required

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: death observed at higher dose of 2000 mg/kg bw/day

Mortality:

One animal at 2000 mg/kg bw/day was killed in extremis four hours after dosing and one animal found dead at 300 mg/kg bw/day on day one of dosing.

Clinical signs:

other: At 2000 mg/kg bw/day: the following were observed; hunched posture, ataxia, pilo-erection, laboured respiration, decreased respiration, gasping respiration and hypothermia. At 300 mg/kg bw/day, hunched posture, ataxia, pilo-erection, lethargy and diuresi

Gross pathology:

Necropsy at 300 mg/kg bw/day, abnormalities noted included; abnormally red lungs, dark liver and dark kidneys. No abnormalities were noted in the animal killed in extremis or killed at the end of the study.

Any other information on results incl. tables

Table 2       Number of animals dead (and with evident of toxicity)

Dose (mg/kg bw)	Mortality (# dead / total)			Time range of deaths (hours)	Number with evident toxicity (# / total)
	Male	Female	Combined		Male	Female	Combined
2000	-	1/ 1	1/ 1	4hr post dosing	-	1/ 1	1 / 5
300	-	1 / 5	1 / 5	Day 1 of dosing	-	1 / 5	1 / 5

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The test item met the criteria for classification of acute toxicity category 4 according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

OECD 420 (2008) - In an acute oral toxicity study, a group of fasted, 8-12 week old female Wistar rats were given a single oral dose of  the test item, CPI-110A at a single dose rate of 2000 mg/kg bw (limit test), after observation of mortality another animal was dosed at 300 mg/kg bw/day and in the absence of mortality, further dosing at similar dosing was conducted in 4 other animals  followed by observed for 14 days.

One animal at 2000 mg/kg bw/day was killed in extremis four hours after dosing and one animal found dead at 300 mg/kg bw/day on the day one of dosing.

At 2000 mg/kg bw/day: the following were observed; hunched posture, ataxia, pilo-erection, laboured respiration, decrease respiration, gasping respiration and hypothermia.  At 300 mg/kg bw/day, hunched posture, ataxia, pilo-erection, lethargy and diuresis.

In addition, there were no treatment related clinical signs, necropsy findings or changes in body weight observed in any of the other animals. All animals showed expected gains in body weight over the observation period.

Necropsy at 300 mg/kg bw/day, abnormalities noted included; abnormally red lungs, dark liver and dark kidneys. No abnormalities were noted in the animal killed in extremis or killed at the end of the study.

Based on condition of the study, the acute oral lethal dose (LD50) of the test item was estimated to be > 300 mg/kg bw/day (GHS classification of category 4). The test item met the criteria for classification of acute toxicity category 4 according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.