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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 January 2005 - 3 February 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 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

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

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:

rat

Strain:

Fischer 344

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Age at study initiation: 9 - 12 weeks
- Weight at study initiation: 120 - 140 g
- Fasting period before study: overnight
- Housing: The animals were singly 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 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 ofthe 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 #5002, Lot Numbers: SEP 23 04 2B and NOV 23 04 3A, were analyzed in October and December 2004, respectively.
- Acclimation period: 8 - 30 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 24°C
- Humidity (%): 30 - 66% relative
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

-Dose Calculations
Individual doses were calculated based on the initial body weights, taking into account the specific gravity (determined by PSL) of the test substance.
-Dosing
The test substance was administered using a stainless steel ball-tipped gavage needle attached to an appropriate syringe. Following administration, each animal was returned to its designated cage. Feed was replaced immediately after dosing.
Individual animals were dosed as follows:

Dosing Animal Dose Level Short Long
Sequence No. (mg/kg) Term Term

1 9996 175 S S
2 110 550 S S
3 122 1,750 S S
4 132 5,000 D D
5 194 1,750 D D
6 327 5,000 S S
7 413 1,750 S S
8 421 5,000 D D
S = Survival
D = Death

The test substance was administered in sequence to the animals as described above. The decision to proceed with the next animal was based on the survival of the previous animal in the short-term period following dosing. Dose progressions and stopping criteria were determined using a statistical program.

Doses:

175 mg/kg, 550 mg/kg, 1,750 mg/kg and 5,000 mg/kg

No. of animals per sex per dose:

175 mg/kg (1 animal); 550 mg/kg (1 animal); 1750 mg/kg (3 animals); 5000 mg/kg (3 animals). All animals were female.

Control animals:

not specified

Details on study design:

-Body Weights
Individual body weights of the animals were recorded prior to test substance administration (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 during the first several hours post-dosing and at least once daily thereafter for up to 14 days after dosing. 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
Surviving rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all decedents and euthanized animals. The external surface of the body and all orifices, tissues, and organs of the thoracic and abdominal cavities were examined.

Statistics:

The Acute Oral Toxicity (Guideline 425) Statistical Program (Weststat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

3 129 mg/kg bw

Based on:

test mat.

95% CL:

> 1 750 - < 5 000

Remarks on result:

other: 95% confidence interval of 1,750 mg/kg (lower) to 5000 mg/kg (upper)

Mortality:

There were no mortalities at dose levels 175 mg/kg (1 animal), 550 mg/kg (1 animal) and 1,750 mg/kg (3 animals).

At the 5,000 mg/kg dose level, all three animals died within 1 day of test substance administration.

Clinical signs:

other: At dose levels 175 mg/kg (1 animal), 550 mg/kg (1 animal) and 1,750 mg/kg (3 animals) all animals appeared active and healthy during the study. There were no signs of gross toxicity, adverse clinical signs, or abnormal behaviour; apart from 1 animal at th

Gross pathology:

At dose levels 175 mg/kg, 550 mg/kg and 1,750 mg/kg no gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

At the 5,000 mg/kg dose level, gross necropsy of the decedents revealed discoloration of the intestines (red).

Any other information on results incl. tables

Individual Body Weights, Doses and Mortality:

Animal No.	Sex	Dose level (mg/kg)	Body weight (g)			Dose	Mortality
			Initial	Day 7	Day 14	mL*	Day
9996	F	175	137	142	160	0.022	E
110	F	550	120	131	157	0.060	E
122	F	1,750	122	150	170	0.20	E
194	F		126	134	151	0.20	E
413	F		140	151	167	0.23	E
132	F	5,000	132	-	-	0.61	0
327	F		130	-	-	0.60	0
421	F		123	-	-	0.56	1

E - Euthanized via CO2 inhalation after weighing on Day 14

*The test substance was administered as received. Specific Gravity 1.090 g/mL.

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 oral LD50 of the test substance was estimated to be 3,129 mg/kg of body weight in female rats with approximate 95% confidence intervals of 1,750 mg/kg (lower) to 5,000 mg/kg (upper).

Executive summary:

Under the conditions of this study, the acute oral LD50 of the test substance was estimated to be 3,129 mg/kg of body weight in female rats with approximate 95% confidence intervals of 1,750 mg/kg (lower) to 5,000 mg/kg (upper). The study was conducted in accordance with U.S. EPA Health Effects Test Guidelines, OPPTS 870.1100 (2002).