3-Pyridinesulfonyl chloride, 2-methoxy-4-(trifluoromethyl)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 January 2005 - 21 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:

2-methoxy-4-(trifluoromethyl)pyridine-3-sulfonyl chloride

EC Number:

606-871-9

Cas Number:

219715-41-0

Molecular formula:

C7H5ClF3NO3S

IUPAC Name:

2-methoxy-4-(trifluoromethyl)pyridine-3-sulfonyl chloride

Test material form:

other: solid

Details on test material:

2-methoxy-4-(trifluoromethyl)pyridine-3-sulfonyl chloride
Appearance: pale tan solid
Storage: room temperature
pH: 7-8 (by wetted pH paper)
Solubility: soluble in methanol, ethanol and acetone
Stability: test material 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
-Strain: New Zealand albino
- 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): Pelleted Purina Certified Rabbit Chow #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): 16 - 22 °C
- Humidity (%): 32 - 62 % relative
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

distilled

Controls:

not specified

Amount / concentration applied:

Prior to application, the test substance was moistened with distilled water to achieve a dry paste by preparing a 65% w/w mixture. Five-tenths of a gram of the test substance (0.77 g of the test mixture) was used.

Duration of treatment / exposure:

4 hours

Observation period:

10 days

Number of animals:

3

Details on study design:

-Preparation and Selection of Animals
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. Three healthy animals without pre-existing skin irritation were selected for test.

-Application of Test Substance
Preliminary solubility testing conducted by PSL indicated mixtures in excess of 65% (i.e., 70%-80%) were too dry to ensure adequate skin contact.
Prior to application, the test substance was moistened with distilled water to achieve a dry paste by preparing a 65% w/w mixture. Five-tenths of a gram of the test substance (0.77 g of the test mixture) was placed on a 1-inch x 1-inch, 4-ply gauze pad and applied to one 6-cm² intact dose site on each animal. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit and they were returned to their designated cages.
After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleansed of any residual test substance.

-Evaluation of Test Sites
Individual dose sites were scored according to the Draize scoring system (see below) at approximately 1, 24, 48, and 72 hours, and at 7 and/or 10 days after patch removal.

-Cage-Side Observations
The animals were 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) to slight 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:

animal #1

Time point:

other: mean score for 24, 48 and 72 hours

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean score for 24, 48 and 72 hours

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean score for 24, 48 and 72 hours

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: mean score for 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: mean score for 24, 48 and 72 hours

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean score for 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Any other information on results incl. tables

Individual skin irritation scores are presented in Table 1 below. A summary of primary skin irritation scores is presented in Table 2.

One test animal was found dead on Day 10. Prior to death, this animal exhibited reduced faecal volume and soft faeces. Gross necropsy of the decedent revealed a fluid-filled abdominal cavity and gaseous distention of the stomach and intestines.

The two surviving animals appeared active and healthy. Apart from the dermal irritation noted below, they did not exhibit signs of gross toxicity, adverse clinical signs, or abnormal behaviour

Within 24 hours of patch removal, all three treated sites exhibited well-defined to moderate erythema and slight edema. The overall incidence and severity of irritation decreased gradually thereafter. Although desquamation was noted at the dose sites beginning on Day 7, the two remaining animals were free of erythema and edema by Day 10 (study termination).

 

Table 1 Individual Skin Irritation Scores:

Erythema/Oedema

Animal Number	Sex	Hours after patch removal				Days
		1	24	48	72	7	10
13484	M	2/2	3/2	3/2	3/2	2/1*	0/0*
13485	M	2/2	3/2	3/2	2/1	2/1	0/0*
13586	M	2/2	2/2	2/1	1/0	0/0	-**
Total		6/6	8/6	8/5	6/3	4/2	0/0
Mean Score		2.0/2.0	2.7/2.0	2.7/1.7	2.0/1.0	1.3/0.7	0.0/0.0

*Desquamation observed.

**Animal was found dead on day 10

 

Table 2 Summary of Primary Skin Irritation Scores:

Average values for three rabbits

	Hours after patch removal				Days
	1	24	48	72	7	10
Erythema	2.0	2.7	2.7	2.0	1.3	0
Oedema	2.0	2.0	1.7	1.0	0.7	0
Total*	4.0	4.7	4.4	3.0	2.0	0

*Total: PDI = average erythema + average oedema

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test substance caused well-defined to moderate erythema and slight edema which cleared by Day 10.

Executive summary:

Under the conditions of this study, the test substance caused well-defined to moderate erythema and slight edema which cleared by Day 10. The study was conducted in accordance with U.S. EPA Health Effects Test Guidelines, OPPTS 870.2500 (1998). The effects seen are therefore considered to be reversible.