2,3,5,6-tetrachloropyridine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 November 1986 to 4 February 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EPA Health Effects Test Guidelines - Office of Toxic Substances; 1982

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,3,5,6-tetrachloropyridine

EC Number:

219-283-9

EC Name:

2,3,5,6-tetrachloropyridine

Cas Number:

2402-79-1

Molecular formula:

C5HCl4N

IUPAC Name:

2,3,5,6-tetrachloropyridine

Details on test material:

Batch muber: T/C 10-17-86.
Purity not specified.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Eight-week-old male and female Fischer 344 rats obtained from Charles River Breeding Laboratories Inc., Kingston, New York, were used for this study. Upon arrival at the laboratory the rats were examined for health status by the laboratory veterinarian. Animals were housed two or three per cage in animal care facilities fully accredited by the American Association for Accreditation of Laboratory Animal Care. The animal rooms of. the testing facility were designed to maintain adequate environmental conditions concerning temperature and humidity.

Purina Certified Rodent Chow #5002 (Ralston Purina Co., St. Louis, MO) and tap_ water were provided ad libitum. Water and feed analyses were performed according to the Standard Operating Procedures of the Mammalian and Environmental Toxicology Research Laboratory. Animals were acclimated to the laboratory environment for at least one week prior to study initiation. Rats were identified by a uniquely numbered metal eartag and randomly assigned by weight to treatment groups. Routine monitoring on weekends/holidays was limited to the removal of dead animals and animal husbandry procedures required to ensure the availability of feed and water.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test material was administered as a 25% (w/v) solution in corn oil. All animals were fasted the night before treatment. Feed was provided to all rats following admin¬istration of the test material.

Doses:

500, 1000 or 2000 mg of the test material per kg body weight by single-dose gavage.

No. of animals per sex per dose:

5 per sex

Control animals:

no

Details on study design:

Five rats per sex received 500, 1000 or 2000 mg of the test material per kg body weight by single-dose gavage. The test material was administered as a 25% (w/v) solution in corn oil. All animals were fasted the night before treatment. Feed was provided to all rats following administration of the test material. A careful clinical examination was made at least once each working day throughout the two-week study. All clinical observations were recorded. Each animal was weighed the day of treatment, and at 1, 7 and 14 days post-treatment. A necropsy was performed on all animals.

Rats that survived the two-week observation period were submitted to necropsy, anesthetized with methoxyflurane and euthanatized. A complete necropsy was conducted by a veterinary pathologist. The necropsy included eye examination with a microscope slide and fluorescent illumination. Rats which died during the observation period were necropsied in a similar manner; however, the eye examination was not done due to post-mortem changes.

Statistics:

Means, and standard deviations of body weights were calculated. The data were evaluated for statistical outliers by a sequential test (Grubbs 1969), however, identified outliers were not excluded from statistical procedures. The LD50 was obtained by nonlinear interpolation (Stephen, 1977).

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 414 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 182 mg/kg bw

Mortality:

There were no mortalities in either sex for animals dosed at 500 mg/kg.

There were two mortalities in female animals dosed at 1000 mg/kg. One died on day 2 and the other on day 3.
There were no mortalities in male animals dosed at 1000 mg/kg.

There were four mortalities in female animals dosed at 2000 mg/kg. One died on day 1 and three died on day 2.
There were five mortalities in male animals dosed at 2000 mg/kg. Four died on day 2 and one died on day 3.

Clinical signs:

other: Clinical observations consisted of lethargy, palpebral closure, lacrimation, laboured respiration, loss of muscle coordination, rough hair coat and facial/perineal soiling. In addition, some rats dosed at 2000 mg/kg were unconscious prior to death. All su

Gross pathology:

Rats that died during the observation period had several nonspecific observations attributed to terminal change and stress. Rats that survived the observation period were within normal limits with the exception of one female rat that had a corneal opacity which was a spontaneous change.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 was calculated as 1414 mg/kg for males and 1182 mg/kg for females.

Executive summary:

An acute oral toxicity study was conducted in accordance with EPA Health Effects Test Guidelines - Office of Toxic Substances; 1982 and the Standard Operation Procedures of the Dow Chemical Company. The acute oral LD50 of the substance was calculated as 1414 mg/kg for males and 1182 mg/kg for females.