Registration Dossier
Registration Dossier
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EC number: 680-378-7 | CAS number: 138624-11-0
Skin irritation / corrosion
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:
- 1 993
- 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 substance name:
- sodium;(4-amino-1-hydroxy-1-phosphonobutyl)-hydroxyphosphinate
- Cas Number:
- 121268-17-5
- Molecular formula:
- C4H12NaNO7P2 · 3 H2O
- IUPAC Name:
- sodium;(4-amino-1-hydroxy-1-phosphonobutyl)-hydroxyphosphinate
- Test material form:
- solid: particulate/powder
Constituent 1
- 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 or test system 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 |
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.
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