WHOLE-BODY AUTORADIOGRAPHIC DISPOSITION, ELIMINATION AND PLACENTAL TRANSPORT OF C-14! TRI-O-CRESYL PHOSPHATE IN MICE

Tri-o-cresyl phosphate (TOCP) is used commercially as a plasticizer an d flame retardant. The disposition, metabolism, elimination and transp lacental uptake of phenyl-U-C-14!TOCP and/or its metabolites, in preg nant and non-pregnant mice, were examined. Pregnant (18th-day gestatio n) and non-pregnant, ICR mice were given an i.v. dose of C-14!TOCP (5 57 muCi kg-1; Specified activity 4.83 muCi mumol-1). At various time i ntervals (1, 24, 48 and 72 h) the animals were processed for whole-bod y autoradiography (WBA). Over 72 h the non-pregnant mice excreted 55% of the C-14 in the urine and 9% in the feces, while excretion in the u rine and feces by the pregnant mice was 50% and 9% of the total dose, respectively. The WBA and its computer-assisted image analysis indicat ed extensive distribution of the C-14 label originally dosed as C-14! TOCP in pregnant mice and their fetuses. The retention of radioactivit y in organs such as lung, spleen, gall-bladder and liver of mother and its fetuses suggest that these are the target sites of TOCP toxicity. The distribution in non-pregnant and pregnant mice and in the fetal t issues followed a similar pattern in uptake and retention until 72 h. Brain and spinal cord had the least amount of C-14!TOCP. This finding may support reports that explain the insensitivity of the mice toward s organophosphate-induced delayed neurotoxicity (OPIDN) of TOCP.