Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
1. In the study, 4 animals/sex/test group were used; however, the guideline recommends 5 animals of one sex in each test group. 2. Abraded and non abraded skin sites were used; however, guideline recommends unabraded skin. 3. Gross necropsy was not perfor
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
This is formulation of 49.2% of the test substance in water.
Specific details on test material used for the study:
- Analytical purity: >93%
- Stability under test conditions: The test substance is hydrolytically and photolytically stable under the conditions of this study and has been shown to be stable in aqueous, alcohol and alcohol/aqueous solutions for extended periods, e.g. at least five years under standard laboratory conditions.

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Test animals:
- Weight at study initiation: 2.2 – 3.4 kg

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Test site
- Area of exposure: Back of animal (10% of body surface)
- Type of wrap if used: The test sites were covered with gauze and each animal was wrapped in a sleeve after application of the test substance
- Type of test site: Intact and abraded (half of the test animals in each sex, i.e., 2 animals/sex/group had their skin abraded on one side )

Removal of the test substance
- Washing (if done): After removal of the dressing, animals were washed with warm water and dried.
- Time after start of exposure: After 24h

Test material
- Amount(s) applied (volume or weight with unit): 3,4 and 5 mL/kg bw
- Concentration (if solution): Undiluted (as received)
- Constant volume or concentration used: yes

Duration of exposure:
24h
Doses:
3,4 and 5 mL/kg bw
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14d
- Frequency of observations and weighing: The animals were observed for clinical signs, mortality and body weight (at the start of the experiment and at termination (Day 14)).
- Necropsy of survivors performed: No

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3.56 mL/kg bw
Based on:
test mat.
95% CL:
>= 3.01 - <= 4.2
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 412.5 mg/kg bw
Based on:
act. ingr.
Mortality:
Mortality observed at each dose levels:
3 mL/kg bw: 1/8
4 mL/kg bw: 6/8
5 mL/kg bw: 7/8
Clinical signs:
Severe erythema and oedema was observed post dosing at the sites of application for all animals in all groups. In the 3 mL/kg bw dose group (i.e., surviving animals), the erythema was followed by thickening of the skin and eschar formation across the back.
Body weight:
A decrease in bodyweight was observed in all surviving animals in all the treatment groups.

Applicant's summary and conclusion

Conclusions:
Under the test conditions, the rabbit acute dermal LD50 of the test substance was found to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw) and after correcting for purity of the active substance, the LD50 was calculated to be 3,412.5 mg/kg bw in rabbits.
Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance (purity > 93%) according to a method similar to EPA OPPTS 870.1200. The experiment was performed in rabbits. The test substance was applied to twelve male and twelve female rabbits (4 animals/sex/test group) at dose levels of 3, 4 and 5 mL/kg bw (single application) on the abraded and intact skin of the back. The test sites were covered with gauze and each animal was wrapped in a sleeve after application for a 24 h period. After removal of the dressing, animals were washed with warm water and dried. The animals were observed for clinical signs and mortality for 14 d. Body weights were determined at the start of the experiment and at termination (Day 14). In the study, 1/8, 6/8 and 7/8 animals died at 3, 4 and 5 mL/kg bw, respectively. Under the test conditions, the acute dermal LD50 of the test substance was found to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw). After correcting for purity of the active substance, the LD50 was calculated to be 3412.5 mg/kg bw (Levenstein, 1977).