HEMATOPOIETIC TOXICITY OF LINOLEIC-ACID ANILIDE - IMPORTANCE OF ANILINE

The purpose of this study was to investigate the role of hydrolysis pr oducts of linoleic acid anilide (LAA), i.e., aniline and linoleic acid (LA), in the toxicity to the hemopoietic system, especially to the sp leen. To achieve this, the parent compound (LAA) and its putative hydr olysis products, i.e., aniline or linoleic acid (LA), were given to ma le SD rats at equimolar doses (0.7 mmol/kg) in 0.25 mi mineral oil by gavage, daily, for 14 days. The controls received equal volumes of veh icle only. Five animals from each group were euthanized at Days 1, 7, and 28 following the last dose. At all time points, spleen weights inc reased in the LAA- and aniline-treated rats, but spleen to body weight ratios were increased only at Days 1 and 7 in these groups. No change s were observed in the LA-treated rats at any time point. RBC counts w ere decreased in the LAA and aniline groups at Days 1 and 7, whereas h emoglobin content was decreased by 20 and 13% in the LAA- and aniline- treated rats, respectively, only at Day 1. Methemoglobin content in th e LAA and aniline groups also increased by 76 and 101%, respectively, at Day 1. Serum transaminases (AST and ALT) decreased in the LAA, anil ine, and LA groups but the decreases were more consistent in the LA gr oup. Serum IgA increased in the LAA and aniline groups only at Day 1. Splenic iron content was increased 381, 486, and 51% in the LAA-treate d rats and 474, 491, and 58% in the aniline-treated rats at Days 1, 7, and 28, respectively. Histopathological changes were confined to the spleen. At Day 1, spleens of both LAA- and aniline-treated rats showed severe vascular congestion and heavy iron deposition. In both groups, vascular congestion diminished by Day 7 and then disappeared by Day 2 8, although iron deposition within red pulp sinusoids appeared to be u nchanged through Day 28. A mild increase in splenic fibrous tissue, wh ich included the capsule, was observed in both LAA and aniline groups at Day 28 only. The similarity in toxic responses of LAA and aniline s upports the concept that LAA is hydrolyzed and released aniline is the putative toxin. Further, iron accumulation in the spleens could also contribute to the toxicity through iron-mediated free radical reaction s. (C) 1995 Society of Toxicology.