3-Pyridinethiol, 2-methoxy-4-(trifluoromethyl)-, lithium salt (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 January 2005 - 12 January 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

lithium(1+) [2-methoxy-4-(trifluoromethyl)pyridin-3-yl]sulfanide

EC Number:

617-976-4

Cas Number:

871544-06-8

Molecular formula:

C7H5NOF3S.Li

IUPAC Name:

lithium(1+) [2-methoxy-4-(trifluoromethyl)pyridin-3-yl]sulfanide

Test material form:

other: aqueous solution

Details on test material:

3-Pyridinethiol, 2-methoxy-4-(trifluoromethyl)-lithium salt
Appearance: dark brown aqueous solution
Storage: room temperature
pH: 11 - 12 (by wetted pH paper)
Solubility: soluble in water, methanol, ethanol, and acetone. Mineral oil: 3-Pyridinethiol, 2-methoxy-4-(trifluoromethyl)-lithium salt soluble, aqueous solution not soluble.
Stability: test substance was expected to be stable for the duration of testing

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Robinson Services, Inc. Clemmons, NC
- Age at study initiation: Young adult
- Housing: The animals were individually housed in suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Purina Certified Rabbit Diet PMI #5322
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by an automatic water dispensing system.
Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analysis of the water is conducted at least once a year and the records are kept on file at Product Safety Laboratories. The most recent analysis was conducted in December 2004. Purina Certified Rabbit Diet, PMI #5322, Lot Number: JUL 06 04 3A, was analyzed in July 2004.
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22°C
- Humidity (%):55 - 56% relative
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL of the test substance was applied as received to each test site.

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours (proposed). Due to the effects seen at the 1-hour observation there was no 4-hour exposure period.

Observation period:

Observations were made after 1 and 24 hours.

Number of animals:

1

Details on study design:

On the day before application, a group of animals was prepared by clipping (Oster model #A5-small) the dorsal area and the trunk. On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. One healthy animal without pre-existing skin irritation was selected for the test.

-Application of Test Substance
Initial testing was conducted on one rabbit to determine the irritation/corrosion potential of the test substance. Three test sites, each approximately 6 cm², were delineated on this rabbit. Five-tenths of a millilitre of the test substance was applied to each dose site and covered with a 1-inch x 1-inch, 4-ply gauze pad. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the patch. The patches were scheduled to be removed at the following intervals: 3 minutes, 1 hour, and 4 hours.

-Evaluation of Test Sites
Individual dose sites were scored according to the Draize scoring system (see below) at approximately 1 and 24 hours after patch removal.

-Cage-Side Observations
The animal was observed for signs of gross toxicity and behavioural changes at least once daily during the test period. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, and coma.

Local dermal irritation was assessed using the prescribed numerical 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) or eschar formation (injuries in depth) 4

Oedema formation:

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

average of three test sites on one animal

Time point:

other: 24 hours

Score:

3

Max. score:

4

Reversibility:

not reversible

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

average of three test sites on one animal

Time point:

other: 24 hours

Score:

1.67

Max. score:

2

Reversibility:

not reversible

Irritant / corrosive response data:

The material is corrosive.

Due to the irritation observed at the 1-hour exposure site after patch removal, the 4-hour patch was removed early resulting in a second 1-hour exposure. All test sites were evaluated for corrosion one hour after patch removal and at approximately 24 hours after removal of the one-hour patch. Due to the development of corrosion following a 1-hour exposure, this study was terminated after the 24-hour evaluation and the animal was euthanized for humane reasons.

Any other information on results incl. tables

The animal appeared active and healthy. Apart from the dermal irritation noted below, there were no other signs of gross toxicity, adverse clinical signs, or abnormal behaviour.

 

Corrosion was defined as full-thickness necrosis of the dose site. The 4-hour patch was removed approximately 5 minutes after the removal of the 1 hour patch due to the corrosion noted at the 1-hour exposure site.

 

Individual Skin Irritation Scores:

Erythema/Oedema

3-Minute Exposure

Animal No.	Sex	1 Hour after patch removal	Hours after removal of last patch
			24
13490	M	2/1	2/1

 

1 Hour Exposure

Animal No.	Sex	1 Hour after patch removal	Hours after removal of last patch
			24
13490	M	4/2*†	4/2†

 

4-Hour Exposure (patch removed after 1 hour due to corrosion noted at 1 hour site)

Animal No.	Sex	1 Hour after patch removal	Hours after removal of last patch
			24**
13490	M	2/1*‡	3/2‡

 

*Shiny skin

†Dark area in dose site

**Animal euthanized for humane reasons

‡Dark area in dose site (pin point)

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test material was determined to be corrosive to the skin.

Executive summary:

Under the conditions of this study, the test material was determined to be corrosive to the skin. The study was conducted in accordance with U.S. EPA Health Effects Test Guidelines, OPPTS 870.2500 (1998).