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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

Constituent 1
Chemical structure
Reference substance name:
N-butyltriphenylphosphonium bromide
EC Number:
918-205-7
Cas Number:
1779-51-7
Molecular formula:
C22H24P.Br
IUPAC Name:
N-butyltriphenylphosphonium 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 levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
186 mg/kg bw
Based on:
test mat.
95% CL:
>= 84 - <= 328
Sex:
male
Dose descriptor:
LD50
Effect level:
130 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no 95% CL calculated
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:
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 5000 mg/kg bw dose groups
- immediately following application, a slight sedation in rats of all dose groups; this symptom was transient in surviving animals
The surviving animals recovered within 11-14 days.
Body weight:
Surviving animals gained body weight during the observation period.
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.