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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-07-04 to 1988-06-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Principles of method if other than guideline:
- Principle of test: To determine the possible dermal irritation of Aledronate Sodium a bone resorption inhibitor, when applied to skin of rabbits for 24 hours.
- Short description of test conditions: A testto determine the skin irritation caused by application of the neat test substance onto shaved and abraded skin of 3 rabbits.
- Parameters analysed / observed: The rabbits were observed daily for systemtic toxicity and mortality, as well as dermal examinations were scored according to the Draize Method.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot No.of test material: Sponsor and 004

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, PA
- Age at study initiation: Approximately 26 weeks
- Weight at study initiation: 3.72 - 3.96 kg
- Housing: stainless steal cages
- Diet (e.g. ad libitum): Certified Purina High Fiber Rabbit Diet ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Pre-determined standards
- Humidity (%): Pre-determined standards
- Air changes (per hr): Pre-determined standards
- Photoperiod (hrs dark / hrs light):Pre-determined standards

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg/site
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: Plastic occlusive wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Cleaned with tap water
- Time after start of exposure: 24 hours

OBSERVATION TIME POINTS
1, 2, 3, 4, 5, 6, 7,8,9,10,11,12,13,14 days

SCORING SYSTEM:
- Method of calculation: Draize Modified Scoring System
A Erythema and eschar formation: Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

B Edema formation:
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-definedby definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond the area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
14 d
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
14 d
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
14 d
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
14 d
Score:
1
Max. score:
1
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
14 d
Score:
1
Max. score:
1
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
14 d
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritant / corrosive response data:
MK-0217 in 24 hours produced well-defined erythema on 2 intact sites and slight edema on 1 site. One rabbit had no signs on the intact site after 24 hours. The incidence and severity of these signs generally increased and all sites had erythema and edema by Day 3. By Day 8 through Day 14 all intact sites had moderate to severe erythema with slight edema observed on 2 sites and moderate edema observed on the third. Wrinkling of several sites was seen starting Day 7 to Day 0 until Day 12, while scaling was observed from Day 10 to Day 14.

Other effects:
- Other adverse systemic effects: MK-0217 produced no observable systemic toxicity throughout the duration of the study.

Any other information on results incl. tables

AS = Abraded Skin / IS = Intact Skin

 Rabbit # and Sex        Type of Irritation Score 24 Hours 2 Days 3 Days 4 Days 5 Days 6 Days  7 Days 8 Days  9 Days    10 Days 11 Days     12 Days     13 Days     14 Days  
AS IS AS IS AS IS AS IS AS IS AS IS

AS

IS

AS

IS

AS

IS

AS

IS

AS

IS

AS

IS

AS

IS

AS

IS

 Male #1   

 Erythema

 4

 0

 4

 0

 4

 2

 4

 2

 *

 *

 *

 *

 4

 3

 4

 3

 4

 3

 4

 3

 4

 3

 4

 3

 4

 3

 4

 3

 Edema

 1

 0

 1

 0

 2

 0

 2

 1

 *

 *

 *

 *

 2

 1

 2

 1

 2

 1

 2

 1

 2

 1

 2

 1

 2

 1

 2

 1

 Female #1   

 Erythema

 2

 2

 2

 2

 2

 2

 3

 2

 *

 *

 *

 *

 3

 3

 3

 3

 3

 4

 3

 4

 3

 4

 3

 4  3  4  3
 Edema  1  0  2  1  3  1  3  1  *  *  *  *  3  1  3  1  3  1  3  1  3  1  3  1  3  1  3  1
 Female #2     Erythema  4  2  4  2  4  3  4  3  *  *  *  *  4  3  4  3  4  3  4  3  4  3  4  3  4  3  4  3
 Edema  2  2  2  2  2  2  3  2  *  *  *  3  2  3  3  3  3  3  3  3  3  3  3  3  3  3  3

 

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
This study found the neat test substance to be extremely irritating to both the intact and abraded skin of rabbits.