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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 January 2005 - 24 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 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Age at study initiation: 9 - 10 weeks
- Weight at study initiation: Males: 198 - 216 g; Females 124 - 133 g
- 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): Certified Rodent Diet (PMI #5002)
- 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 Rodent Diet, PMI 45002, Lot Numbers: SEP 23 04 2B and NOV 23 04 3A, were analyzed in October and December 2004, respectively.
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22°C
- Humidity (%): 30 - 67% relative
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

distilled

Details on dermal exposure:

-Preparation and Selection of Animals
On the day prior to application, a group of animals was prepared by clipping (Oster model #A5-small) the dorsal area and the trunk. After clipping and prior to application, the animals were examined for health, weighed (initial) and the skin checked for any abnormalities. Ten healthy rats (five males and five females) were selected for test.

-Dose Calculations
Individual doses were calculated based on the initial body weights, taking into account the concentration of the test mixture.

-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 thousand mg/kg of body weight of the test substance was then applied to a 2-inch x 3-inch, 4-ply gauze pad and placed on a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface). The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rats were then returned to their designated cages. The day of application was considered Day 0 of the study.

After 24 hours of exposure to the test substance, the pads were removed and the test sites were cleansed of residual test substance.

Duration of exposure:

24 hours

Doses:

1 dose at 5000 mg/kg/bw

No. of animals per sex per dose:

5 male
5 female

Control animals:

no

Details on study design:

-Body Weights
Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination).
-Cage-Side Observations
The animals were observed for mortality, signs of gross toxicity, and behavioural changes for several hours after application and at least once daily thereafter for 14 days. 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.
-Necropsy
All rats were euthanized via CO2 inhalation on Day 14. Gross necropsies were performed on all animals. The external surface of the body and all orifices, tissues, and organs of the thoracic and abdominal cavities were examined.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: None of the animals died and there were no signs of gross toxicity, dermal irritation, adverse clinical signs or abnormal behaviour.

Mortality:

All animals survived.

Clinical signs:

other: There were no signs of gross toxicity, dermal irritation, adverse clinical signs or abnormal behaviour.

Gross pathology:

No gross abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute dermal LD50 of the test substance was determined to be greater than 5,000 mg/kg of body weight in male and female rats.

Executive summary:

Under the conditions of this study, the acute dermal LD50 of the test substance was determined to be greater than 5,000 mg/kg of body weight in male and female rats. The study was conducted in accordance with U.S. EPA Health Effects Test Guidelines, OPPTS 870.1200 (1998).