Abstract
Administration of up to 8 g/kg of MAAQ orally to dogs in a 24 hour period did not result in any signs of intoxication, any significant changes in clinical pathology values of the blood or any pathological changes in tissues at necropsy. The acute oral LD(,50) and the acute minimum toxic dose were estimated to be greater than 8 g/kg in the dog. Topical application of MAAQ to the skin and eyes of rabbits did not produce signs of irritation or systemic toxicity when applied at the rate of 50 mg of MAAQ/eye or 2 g of MAAQ/kg on the shaved and abraded back. Oral exposure of sheep to MAAQ (100 mg/kg) followed by exposure to sunlight for 10 days did not result in evidence of photosensitization. Topical application of MAAQ to the shaved backs of rabbits (approximately 0.1 ml of a saturated ethyl alcohol solution/1 cm('2) spot) did not result in evidence of photosensitization after exposure to a Wood's UV lamp or a sun tanning UV lamp. A procedure using Sep Pak('R) C(,18) cartridges for preparation, and TLC for separation, was developed to isolate the major colored urinary metabolites from the urine of a sheep given 50 mg of MAAQ/kg. MS and NMR were used to identify the colored urinary metabolites of MAAQ as: 1-aminoanthraquinone, 4-hydroxy-1-aminoanthraquinone, 2-hydroxy-1-aminoanthraquinone, the glucuronic acid conjugate of each of these and the glucuronic acid conjugate of MAAQ. A visible light spectrophotometric technique was developed to quantitate MAAQ and its 7 identified colored metabolites. Within 96 hours of dosing a sheep with 50 mg of MAAQ/kg, 27.39% of the dose was accounted for by MAAQ and its metabolites in the urine and 16.06% of the dose was accounted for by MAAQ in the feces. Small ((mu)g/ml) quantities of the glucuronide conjugates of the 2-hydroxy and 4-hydroxy metabolites were detected in the milk. Very small (<1 (mu)g/g) quantities of the free and conjugated metabolites were found in the bile, kidney and liver. It was concluded that MAAQ is a relatively non-toxic chemical. Glucuronic acid conjugation is the major pathway of its metabolism and it is rapidly excreted, primarily in the urine, with no apparent storage in the tissues.
Martin, Bruce Warren (1982). The toxicity and metabolism of 1-methylaminoanrthraquinone. Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -349792.