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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A single dose of the test substance was applied to the shaved, abraded skin of 5 male and 5 female New Zealand White rabbits at a dosage of 2000 mg/kg of body weight. The application site was occluded for 24 hours. The rabbits were weighed and observed for 14 days (weekends excluded) following removal of the test material. At the end of the observation period, 2 male and 2 female rabbits were killed and examined for gross and histomorphologic changes.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
-Purity: 96.8%

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Buckshire Corporation, Perkasie, Pennsylvania
- Females (if applicable) nulliparous and non-pregnant: No data are provided in the report
- Age at study initiation: Young adult
- Weight at study initiation: The rabbits weighed between 2366 and 2927 grams on the day of dosing
- Fasting period before study: No data are provided in the report
- Housing: The rabbits were housed singly in suspended, stainless steel, wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow® #5322
- Water (e.g. ad libitum): Source of water was not provided in the report
- Acclimation period: Two weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 2°C
- Humidity (%): 50% ± 10%.
- Air changes (per hr): No data are provided in the report
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: The aliquot of test material designated for an animal was moistened with dimethyl phthalate to form a paste
Details on dermal exposure:
TEST SITE
- Area of exposure: Approximately 190 square centimeters
- % coverage: 190 square centimeters is approximately equal to 10 percent of
the total body surface area of rabbits in the 2 - 3 kg body weight range
- Type of wrap if used: The rabbits were then wrapped with successive layers of plastic film, stretch gauze bandage and elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Excess test material was wiped from the animals' backs with dry paper towels
- Time after start of exposure: Approximately 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg of body weight
- Concentration (if solution): Paste
- Constant volume or concentration used: yes
- For solids, paste formed: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 male and 5 female rabbits per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed approximately every other day (weekends excluded) until the 14th day post application
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross and histopathology
Statistics:
No

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no deaths at highest dose tested
Mortality:
No rabbits died within 14 days after application of 2000 mg/kg of test substance
Clinical signs:
Clinical observations during the study were limited to body weight effects; no other clinical signs of toxicity were observed in any rabbit throughout the study
Body weight:
Slight or moderate weight losses (up to 9% of initial body weight) occurred in the rabbits the day after application of the test material (see tables for male and female rabbits in the "Any other information on results including tables" section
Gross pathology:
No gross or microscopic compound-related effects' were observed in rabbits killed 14 days after treatment
Other findings:
One rabbit exhibited severe erythema 1 day after application; the skin appeared normal at 3 days. No other dermal irritation was present throughout the remainder of the test

Any other information on results incl. tables

Individual body weights (g) of male rabbits after dermal exposure to the test substance

 

Animal #

Initial body weight

Body weight on day 1

Body weight on day 3

Body weight on day 6

Body weight on day 8

Body weight on day 10

Body weight on day 13

Body weight on day 14

19881

2524

2415

2569

2711

2766

2808

2961

3035

19882

2460

2427

2475

2634

2687

2724

2723

2769

19883

2366

2273

2379

2409

2537

2611

2694

2734

19884

2563

2514

2634

2643

2745

2852

2939

2950

19885

2927

2904

2975

2959

3023

3050

3074

3071

 

Individual body weights (g) of female rabbits after dermal exposure to the test substance

 

Animal #

Initial body weight

Body weight on day 1

Body weight on day 3

Body weight on day 6

Body weight on day 8

Body weight on day 10

Body weight on day 13

Body weight on day 14

19840

2746

2714

2888

2818

2920

2978

2973

3059

19841

2927

2900

3048

3096

3132

3190

3198

3102

19842

2862

2602

2861

2934

2972

3058

3123

3115

19843

2508

2508

2652

2611

2731

2756

2771

2825

19844

2609

2557

2696

2704

2856

2991

2986

2992

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for male and female New Zealand White rabbits was greater than 2000 mg/kg of body weight.
Executive summary:

A single dose of the test substance was applied to the shaved, abraded skin of 5 male and 5 female New Zealand White rabbits at a dosage of 2000 mg/kg of body weight. The application site was occluded for 24 hours. The rabbits were weighed and observed for 14 days (weekends excluded) following removal of the test material. At the end of the observation period, 2 male and 2 female rabbits were killed and examined for gross and histomorphologic changes.

 

No rabbits died within 14 days after dosing. Slight or moderate weight losses (up to 9% of initial body weight) occurred in the rabbits the day after application of the test material. One rabbit exhibited severe erythema 1 day after application; the skin appeared normal at 3 days. No other dermal irritation was present throughout the remainder of the test. No gross or microscopic compound-related effects' were observed in rabbits killed 14 days after treatment.

 

Under the conditions of this test, the skin absorption LD50 was greater than 2000 mg/kg of body weight, the highest dose tested.