Whole-body autoradiographic disposition, elimination and placental transport of [14C]tri-o-cresyl phosphate in mice.

Abstract

Tri-o-cresyl phosphate (TOCP) is used commercially as a plasticizer and flame retardant. The disposition, metabolism, elimination and transplacental uptake of [phenyl-U-14C]TOCP and/or its metabolites, in pregnant and non-pregnant mice, were examined. Pregnant (18th-day gestation) and non-pregnant, ICR mice were given an i.v. dose of [14C]TOCP (557 microCi kg-1; Specified activity 4.83 microCi mumol-1). At various time intervals (1, 24, 48 and 72 h) the animals were processed for whole-body autoradiography (WBA). Over 72 h the non-pregnant mice excreted 55% of the 14C in the urine and 9% in the feces, while excretion in the urine and feces by the pregnant mice was 50% and 9% of the total dose, respectively. The WBA and its computer-assisted image analysis indicated extensive distribution of the 14C label originally dosed as [14C]TOCP in pregnant mice and their fetuses. The retention of radioactivity 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 tissues followed a similar pattern in uptake and retention until 72 h. Brain and spinal cord had the least amount of [14C]TOCP. This finding may support reports that explain the insensitivity of the mice towards organophosphate-induced delayed neurotoxicity (OPIDN) of TOCP.