Monkey liver

Experiments with monkeys given intramuscular injections of a mineral oil emulsion with [l-14C] -hexa-decane tracer provide data illustrating that absorbed C-16 hydrocarbon (a major component of liquid petrolatum) is slowly metabolized to various classes of lipids (Bollinger 1970). Two days after injection, substantial portions of the radioactivity recovered in liver (30%), fat (42%), kidney (74%), spleen (81%), and ovary (90%) were unmetabolized -hexadecane. The remainder of the radioactivity was found as phospholipids, free fatty acids, triglycerides, and sterol esters. Essentially no radioactivity was found in the water-soluble or residue fractions. One or three months after injection, radioactivity still was detected only in the fat-soluble fractions of the various organs, but 80-98% of the detected radioactivity was found in non-hydrocarbon lipids. 

Figure 24 HPLC spectrum resulting from the incubation of the oxadiazole with monkey liver microsomes.

Screening is usually carried out with liver microsomes from humans, rats, mice, dogs and monkeys and liver S9 fraction from aroclor 1254-induced rats. The incubation is typically mn with a volume of 0.2-1. OmL in a microcentrifuge or a glass tube. Different incubation conditions are used for CYP and UGT reactions. The incubation mixture for formation of oxidative metabolites and/or GSH conjugates contains ... 

Figure 9.4 Formation of M3 via biotranformation of BMS-1 with monkey liver microsomes... 

Distribution studies by whole-body autoradiography in rats and monkeys revealed accumulation of radiolabel in the liver, kidney, lung, adrenal cortex and stomach. In fetuses exposed in utero, only the eye lens accumulated radiolabel at a higher concentration than that observed in maternal blood (Sandberg and Slanina 1980). 

Repeat dose pharmacokinetic studies were undertaken in Sprague-Dawley rats and in monkeys. Biodistribution studies were carried out in both normal and knockout mice, with the majority of product distributed to the liver. No specific studies on product metabolism or excretion were undertaken, as the protein is almost certainly degraded via normal protein degradation mechanisms. 

These values are supported by the results of subchronic studies with squirrel monkeys and dogs (Jones et al. 1972). Monkeys and dogs exposed continuously at approximately 15 ppm for 90 d showed no overt clinical signs systemic toxicity consisted of biochemical and/or non-life-threatening histological changes in the liver, spleen, and kidneys. 

---