Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 10 September to 2 November 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted similarly to OECD Guideline 404 with minor deviations: no certificate of analysis; 4 test sites used: 2 for 4-h exposure, 2 for 24-h exposure; animals not weighed
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
no certificate of analysis; 4 test sites used: 2 for 4-h exposure, 2 for 24-h exposure; animals not weighed
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
2-hydroxy-4-(methylthio)butyric acid
EC Number:
209-523-0
EC Name:
2-hydroxy-4-(methylthio)butyric acid
Cas Number:
583-91-5
Molecular formula:
C5H10O3S
IUPAC Name:
2-hydroxy-4-(methylthio)butanoic acid
Details on test material:
- Name of test material (as cited in study report): Alimet
- Source: Monsanto Company
- Physical state: Amber liquid
- Lot/batch No.: CBA 0824AL1
- Storage condition of test material: Room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton-Dutchland, Inc., Denver, USA
- Age at study initiation: Young adults
- Housing: Individually housed in suspended, stainless steel cages
- Diet (e.g. ad libitum): Lab Rabbit Chow HF (Purina #5326), ad libitum
- Water (e.g. ad libitum): Municipal water supply, ad libitum
- Acclimation period: 29 or 43 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60-70 °F
- Humidity (%): 30-70%
- Photoperiod (h dark / h light): 12 h dark / 12 h light

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume with unit): 0.5 mL/site
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
4 males and 2 females
Details on study design:
TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: 10% of body surface area
- Type of wrap if used: Test material was applied beneath a gauze (1” X 1”), placed directly on the test sites and then covered with porous tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites gently wiped free of excess test material using a paper towel and water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scoring system

ERYTHEMA AND ESCHAR FORMATION:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness): 4
Eschar (scab) formation: 4E
Necrosis: 4N
Superficial necrosis: 4S

OEDEMA FORMATION:
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 mm): 3
Severe oedema (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:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.61
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.03
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
- Mild and transient irritation; no tissue destruction
- Mean individual scores at 24, 48 and 72 hours after exposure for the 6 animals were 1.5, 1.8, 1.5, 1.7, 1.5, 1.7 for erythema score and 0, 0, 0, 0, 0.2, 0 for oedema score
- See table 1 for further details
Other effects:
No data

Any other information on results incl. tables

Table 1: Dermal irritation scores*

Animal No.

Site

30 min.

24 h

48 h

72 h

Day 7

Erythema

 

4951 M

Front right

2

2

1

0

-

Front left

2

2

2

2

0

4952 F

Front right

2

2

2

1

0

Front left

2

2

2

2

0

4953 M

Front right

2

2

2

1

0

Front left

2

2

1

1

0

4975 M

Front right

2

2

2

1

0

Front left

2

2

2

1

0

4989 M

Front right

2

2

2

1

0

Front left

2

2

1

1

0

4990 F

Front right

2

2

2

1

0

Front left

2

2

2

1

0

Oedema

 

4951 M

Front right

0

0

0

0

-

Front left

-

-

-

-

0

4952 F

Front right

0

0

0

0

0

Front left

1

0

0

0

0

4953 M

Front right

0

0

0

0

0

Front left

1

0

0

0

0

4975 M

Front right

1

0

0

0

0

Front left

0

0

0

0

0

4989 M

Front right

1

0

0

0

0

Front left

1

1

0

0

0

4990 F

Front right

1

0

0

0

0

Front left

0

0

0

0

0

* noted at 30 min, 24, 48 and 72 hours and Day 7 after removal of test material;

- = Observation not present

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, Alimet is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).
Executive summary:

In a primary dermal irritation study performed similarly to OECD guideline 404, six (4 males and 2 females) New-Zealand White rabbits were dermally exposed to 0.5 mL of Alimet, under a semi-occlusive bandage for 4 hours to clipped skin of the back (10% of the body surface area). Animals then were observed for 7 days. Irritation was scored by the method of Draize (1959).

Mild to moderate irritation was observed at the application sites which subsided within 7 days. Mean individual scores at 24, 48 and 72 hours after removal of the test material for the 6 animals were 1.5, 1.8, 1.5, 1.7, 1.5, 1.7 for erythema score and 0, 0, 0, 0, 0.2, 0 for oedema score. In this study, alimet is not a dermal irritant on male/female rabbits.

 

Under the test conditions, Alimet is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).