ACUTE AND CHRONIC EFFECTS OF PENTACHLOROPHENOL AND SODIUM PENTACHLOROPHENATE UPON EXPERIMENTAL ANIMALS

¹ From the Kettering Laboratory of Applied Physiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio

1. Pentachlorophenol and sodium pentachlorophenate, when absorbed in sufficient quantity into the tissues of dogs, rabbits, rats and guinea pigs, produce an acute toxic state characterized by accelerated respiration, moderately elevated blood pressure, hyperpyrexia, hyperglycemia and glycosuria and hyperperistalsis (vomiting was observed in dogs after a subcutaneous dose). The urinary output is at first increased, later diminished, and there is a rapidly developing motor weakness which in fatal cases terminates in asphyxial convulsions and cardiac and muscular collapse. Rigor mortis is immediate and profound.

2. Irritation of the skin and marked local damage followed by complete recovery is the usual result of cutaneous application of single or repeated doses of pentachlorophenol in fuel oils. Single and repeated applications of aqueous solutions of the salt may cause mild local damage.

3. A gradual loss of weight but no significant changes in the hemoglobin content of the blood are noted in rabbits given repeated, slightly sublethal doses of the salt. The numbers of erythrocytes and of various types of leukocyte remain within normal limits. Rectal temperatures and blood sugar values rise markedly after the administration of single sublethal doses but fail to show such elevations when the doses are repeated.

4. Absorption of sodium pentachlorophenate through the skin of the rabbit cannot be detected by blood analyses following a single one-hour application of 100 mgm. of this salt. Repeated applications of this quantity result in demonstrable absorption, the blood level rising to about 0.45 mgm.%. (This is approximately one-fifteenth of the concentration of pentachlorophenol encountered in the blood at the time of the appearance of symptoms following a lethal oral dose.)

5. Absorption of sodium pentachlorophenate from the stomach of the rabbit starts almost immediately after administration of a single dose of 18 mgm. per kilogram, reaching a peak of 2.4 mgm.% in the blood (with a dose of 37 mgm./kg) in about 7 hours. Four days elapse before all traces of the compound disappear from the blood. The daily administration to rabbits (by stomach tube) of quantities of the salt equivalent to 3 mgm. of pentachlorophenol per kilogram leads to a blood level of about 0.6 mgm.%. Feeding of the salt (mixed with food) in a dosage of 3.9 mgm. per rat per day apparently causes no tissue damage but results in inadequate consumption of food, presumably because of the unpleasant taste which the compound imparts to the diet. Cats refuse food altogether when it contains about 5 mgm. pentachlorophenol per 100 gram of salmon or meat. A tolerance develops in rabbits when sublethal oral doses are administered repeatedly.

6. Within the limits of dosages employed, approximately 70% of orally administered sodium pentachlorophenate is excreted in the urine by the rabbit (the bulk of it in the first 24 hours); about 9% is broken down, and about 6% is in the gastrointestinal tract at the end of the first day, the remainder being well distributed throughout the tissues. Very small amounts are excreted with the feces. In the rat, following the intraperitoneal injection of 40 mgm. per kilogram only about 13% of the amount administered is excreted, 40% is broken down, and about 47% remains in the tissues at the end of the first day. Pentachlorophenol is not detoxified by conjugation with sulfuric or glucuronic acid.

7. Soap and plenty of water is a more effective agent than alcohol for the removal of pentachlorophenol or sodium pentachlorophenate from the skin.