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Description of key information

Oral LD50 (rat, m/f): 186 mg/kg bw (OECD 401)

Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402)

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:
1984-07-18 to 1984-08-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
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
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)
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.

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

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.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
186 mg/kg bw
Quality of whole database:
Data from a guideline study with reliability 1.

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:
1984-07-17 to 1984-07-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1984
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
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: 183 - 215 g
- Fasting period before study: no
- 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
Type of coverage:
semiocclusive
Vehicle:
other: distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Details on dermal exposure:
TEST SITE
- Area of exposure, pretreatement: Approximately 24 hours before treatment an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper.
- % coverage: no data
- Type of wrap if used: The required amount of the test substance was evenly dispersed on the skin. It was covered with a gauze lined semiocclusive dressing, which was fastened around the trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with lukewarm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): n.a.
- Constant volume or concentration used: n.a.
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): no data, however vehicle distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80 was used in an amount sufficient to form a paste only
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
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.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
No animal died.
Clinical signs:
Sedation on exposure day, dyspnoe from exposure day to post-exposure day 13, exopthalmus on post-exposure days 1-4, ruffed fur from exposure day to post-exposure day 12, ventral body posture from exposure day to post-exposure day 1 and curved body posture on post-exposure days 1-6
No cutaneous changes which could be related to the treatment were observed.
Body weight:
Surviving animals gained body weight during the observation period.
Gross pathology:
No treatment-related deviations from normal morphology could be detected.
Interpretation of results:
GHS criteria not met
Conclusions:
Dermal LD50 > 2000 mg/kg bw; classification criteria of REGULATION (EC) No 1272/2008 as well as of the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations no met.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Data from a guideline study with reliability 1.

Additional information

In an acute oral toxicity study according to OECD guideline 401 (1984), n-Butyltriphenylphosphonium bromide was administered by oral gavage at doses of 100, 300, 1000 and 5000 mg/kg bw to five rats per sex per dose. The fasted, 7-8 weeks old rats were given a single oral dose of n-Butyltriphenylphosphonium bromide in distilled water containing 0.5% carboxymethyl cellulose end 0.1% polysorbate 80 at dose volume of 20 mL/kg body weight at the dose of 5000 mg/kg bw and 10 mL/kg bw at all other dose levels. All animals were subjected to daily observations. Body weight was recorded on days 1, 7, 14 and at death. Macroscopic examination was performed on the day of death or after terminal sacrifice (day 14). All rats treated with 1000 or 5000 mg/kg body weight were found dead within 1 hour after treatment, in the dose group 300 mg/kg bw 4/5 males and 2/5 females died within 3 hours after treatment. In the lowest dose group on male was found death within 1 hour after treatment and a further male on day 6 and one female on day 9. Dyspnoea, exophthalmus, ruffed fur and curved position are symptoms commonly seen during the observation time. In addition, a slight sedation in rats of all dose groups immediately following application, and clonic-tonic convulsions preceding early death in the 2000 and 5000 mg/kg bw dose groups were considered to be treatment related. The surviving animals showed body weight gain during the observation period and recovered within 11-14 days. No treatment-related deviations from normal morphology could be detected. 

Oral LD50 (rat, m/f): 186 (95% CL 84-328) mg/kg bw.

In an acute dermal toxicity study according to OECD guideline 402 (1984), n-Butyltriphenylphosphonium bromide was administered dermally for 24 hours at a dose of 2000 mg/kg bw to five rats per sex. Approximately 24 hours before treatment an area on the back of the 7-8 weeks old rat of at least 10% of the body surface was shaved with an electric clipper. The rats were given a single dermal dose of n-Butyltriphenylphosphonium bromide moistened with distilled water containing 0.5% carboxymethyl cellulose end 0.1% polysorbate 80. The treated skin was covered with a gauze lined semiocclusive dressing, which was fastened around the trunk with an adhesive elastic bandage. After an exposure period of 24 hours the dressing was removed and the skin was cleaned with lukewarm water. All animals were subjected to daily observations. Body weight was recorded on days 1, 7, 14 and at death. Macroscopic examination was performed on the day of death or after terminal sacrifice (day 14). All rats survived until terminal sacrifice. Dyspnoea, exophthalmus, ruffed fur and curved position are symptoms commonly seen during the observation time. Except for this, neither unusual symptoms nor cutaneous changes which could be related to the treatment were observed. The animals showed body weight gain during the observation period and recovered within 14 days. No treatment-related deviations from normal morphology could be detected. 

Dermal LD50(rat, m/f): > 2000 mg/kg bw.

Justification for classification or non-classification

Oral LD50 rat 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.

n-Butyltriphenylphosphonium bromide is not classified for dermal acute toxicity because dermal LD50 rat is > 2000 mg/kg bw.

n-Butyltriphenylphosphonium bromide is not classified for inhalative toxicity because of lacking data.