(4-carboxybutyl)triphenylphosphonium bromide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984-07-18 to 1984-08-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1984

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

butyl(triphenyl)phosphonium bromide

EC Number:

918-205-7

Cas Number:

1779-51-7

Molecular formula:

C22H24P.Br

IUPAC Name:

butyl(triphenyl)phosphonium bromide

Test animals

Species:

rat

Strain:

other: Tif:RAIf (SPF), F3-crosses of RII 1/TIF x RII 2/Tif

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species: Rat, Tif:RAIf (SPF), F3-crosses of RII 1/TIF x RII 2/Tif
- Age at study initiation: approximately 7-8 weeks old
- Weight at study initiation: 167 - 209 g
- Fasting period before study: Food was withheld overnight prior to dosing.
- Housing: 5 animals/sex/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3
- Humidity (%): 55 +/- 15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water containing CMC (carboxymethyl cellulose) and polysorbate 80

Details on oral exposure:

Vehicle: Distilled water containing 0.5% carboxymethyl cellulose and 0.1% polysorbate 80 (prepared by Pharmaceutical Division, Ciba-Geigy Ltd.).
Volume (mL/kg body weight) applied: 20 at the highest dose, 10 at all other doses.

Doses:

100, 300, 1000 and 5000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Mortality/Viability: Twice daily on working days, once on weekend days
Body weights: Days 1 (pre-administration), 7, 14 and at death
Clinical signs: daily
Necropsy: Spontaneously dying animals were submitted to a group necropsy as soon as possible; survivors at the end of the observation period.
Observation period: 14 days

Statistics:

From the body weights, the group means and their standard deviations were calculated.
Where feasible, the LD50 including the 95% confidence limit were computed by the logit method (J. Berkson, J.Am. Stat. Ass. 39. 357-65, 1944)

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

186 mg/kg bw

Based on:

test mat.

95% CL:

>= 84 - <= 328

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

130 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no 95% CL calculated

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

263 mg/kg bw

Based on:

test mat.

95% CL:

>= 87 - <= 907

Mortality:

See table in section "Any other information on results incl. tables"

Clinical signs:

other: Dyspnoea, exophthalamus, ruffed fur and curved position are symptoms commonly seen during the observation time. In addition the following symptoms were considered to be treatment related: - clonic-tonic convulsions preceding early death in the 2000 and 50

Gross pathology:

No treatment-related deviations from normal morphology could be detected.

Any other information on results incl. tables

The incidence of mortality

Dose level (mg/kg bw)	Mortality males	Mortality females	Time of death (day(s))
100	2/5	1/5	1, 6, 9
300	4/5	2/5	1
1000	5/5	5/5	1
5000	5/5	5/5	1

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

 Oral LD50 186 mg/kg bw; acute oral toxicity category 3 based on the criteria of REGULATION (EC) No 1272/2008 as well as the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.