Reaction mass of 2-hydroxy-4-(methylthio)butanoic acid and 2-hydroxy-4-(methylthio)butanoic acid dimer

Skin irritation / corrosion

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

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

Test material information

Constituent 1

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

Results

Results 1

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

Results 2

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).