Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrabutylphosphonium chloride
EC Number:
218-964-8
EC Name:
Tetrabutylphosphonium chloride
Cas Number:
2304-30-5
Molecular formula:
C16H36P.Cl
IUPAC Name:
tetrabutylphosphanium chloride
Test material form:
other: waxy solid
Details on test material:
- Name of test material (as cited in study report): CYPHOS 443
Specific details on test material used for the study:
Purity > 98%

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.3 - 3.2 kg
- Acclimation period: 14 days

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: Ethylene carbonate
Remarks:
The substance was tested both with and without vehicle.
Details on dermal exposure:
TEST SITE
- Area of exposure: no less than 10% of the body surface area was available for application
- Type of wrap if used: The trunk of each animal was wrapped with an impermeable plastic film of Saran Wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg
- Concentration (if solution): 11.9 to 66.8% w/w
- Constant volume used: yes
Duration of exposure:
24h
Doses:
Tetrabutylphosphonium chloride with Ethylene carbonate: 159, 302, 506, 676, 862 and 1368 mg/kg
Pure Tetrabutylphosphonium chloride: 100, 200, 300 and 400 mg/kg
No. of animals per sex per dose:
4
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for any signs of systemic toxicity and/or death frequently during the day of administration and thereafter, at least twice a day for 14 days. Body weights were recorded just prior to dosing and again on day 7 and day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Gross necropsy and examination were performed on each animal, whether it died during the study or was killed at the end of the study. The brain with spinal cord, heart, each kidney, spleen, liver and lungs were weighed.
Statistics:
Each LC50 was calculated according to the method of Litchfield and Wilcoxon. The results of the quantitative continuous variables, such as body weight and organ weight changes, were intercompared for the test groups versus the control group by analysis of variance and by a multiple range test. These analyses included all animals alive at the appropriate weighing time. When a significant F value in the analysis of variance was observed, the latter test was employed to determine which group (or groups) differed significantly from which other group (groups).

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
225 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Pure substance
Sex:
male
Dose descriptor:
LD50
Effect level:
600 mg/kg bw
Based on:
test mat.
Remarks on result:
other: with EC as a vehicle
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: with EC as a vehicle
Mortality:
See tables below for details. Death was preceded by cyanosis and convulsion, and occurred within 24h of dosing.
Clinical signs:
Clinical signs of Bu4PCl toxicity included weight loss, ataxia, hypotonia (head and ear droop), and labored breathing. These signs persisted for 2-4 days in surviving males and for 1-9 days in surviving females.
Body weight:
The mean male body weights of the 506, 676 and 862 mg/kg test groups was significantly lower than those of the 1368 mg/kg test group and the control group. The mean female body weights of the 506, 676 and 862 mg/kg test groups were significantly lower than those of the 158, 302 mg/kg test groups and the control groups.
Gross pathology:
The mean male kidney weight/body weight ratios for both kindeys of the 506 and 862 mg/kg test groups were significantly increased as compared to those of the 676, 1368 mg/kg test groups and the control group. The mean male brain with spinal cord weight/body weight ratio of the 862 mg/kg exposure group was significantly higher than those of the 506, 676, 1368 mg/kg test groups and the control group. The mean female brain with spinal cord weight/body weight ratios of the 505, 676 and 862 mg/kg test groups were significantly higher than those of the 158, 302 mg/kg test groups and the control group.
The other mean organ weights (absolute and organ wt/body wt ratios) of rabbits receiving applications of Bu4PCl were comparable to controls.

Any other information on results incl. tables

BU4PCl with EC
Application in mg/kg Number of dead/Number of dosed
Male Female
159 0/4 0/4
302 * 0/4
506 * 2/4
676 3/4 4/4
862 3/4 4/4
1368 4/4 *
LD50 600 500
mg/kg mg/kg

* Dose not tested

Pure BU4PCl
Application in mg/kg Number of dead/Number of dosed
Male
100 0/5
200 0/5
300 3/5
400 5/5
LD50 600
mg/kg

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The LD50 for acute dermal exposure with the ethylene carbonate vehicle was 500-600 mg/kg. However, the LD50 by acute dermal exposure of undiluted compound was 225 mg/kg.
Executive summary:

The acute dermal toxicity of Tetrabutylphosphonium chloride was tested according to acceptable scientific standards. The product was tested in ethylene carbonate as a vehicle but also as the pure undiluted substance.

Tetrabutylphosphonium chloride was applied to the skin of 4 or 5 rabbits of each sex at 159, 302, 506, 676, 862 and 1368 mg/kg in the vehicle or at 100, 200, 300 and 400 mg/kg as a pure compound for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Necropsy was performed upon death or after terminal sacrifice at the end of the study period.

The LD50 for acute dermal exposure with the ethylene carbonate vehicle was 500 (female) -600 (male) mg/kg. However, the LD50 by acute dermal exposure of undiluted compound was 225 mg/kg (male).

Based on these results, Tetrabutylphosphonium chloride should be classified as Category 3 for acute dermal toxicity according to the CLP and the UN GHS.

Categories Display