Dose-dependent milk transfer and tissue distribution of the food mutagen PhIP in rats and their suckling pups

Abstract

The transfer of the neonatal carcinogen and food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) into milk of lactating Sprague-Dawley rats and the uptake in 10 day old suckling pups were investigated. PhIP was quantified by HPLC. In dams given a single i.v. injection of PhIP (0.5 mg/kg body wt) and milked 1 h later, 0.04-0.16% of the dose per ml milk was excreted. In dams dosed i.v. with PhIP (0, 0.05, 0.5 and 5.0 mg/kg body wt) and killed 4 h later a linear dose-dependent milk excretion and uptake of PhIP in the tissues were observed (y = 76.1 chi + 1.0; r = 0.94; P < 0.001). In addition, a linear correlation was found between PhIP levels in dam's liver and milk (y = 0.61 chi + 37.4; r = 0.97; P < 0.001). Following administration of PhIP at doses of 0.05 and 0.5 mg/kg body wt, the highest level of PhIP was observed in the milk samples. Following injection of 5.0 mg PhIP/kg body wt, the highest level of PhIP was observed in the mammary gland and liver. The milk/plasma ratio was 9.3 +/- 6.8 at the highest dose at 4 h. High levels of unmetabolized PhIP were also detected in liver and blood of pups allowed to suck the PhIP-dosed dams for 3 h. Autoradiography of pups injected i.p. with [2-14C]PhIP (4.8 mg/kg body wt) showed that only a low level of radioactivity was irreversibly bound in the liver, and high levels of radioactivity were found in stomach milk, intestinal contents and in the urine, 1 h and 4 h following injection. In addition, radioactivity was present in the skin, liver and kidney. Since milk is the major dietary source for nursing infants, the milk transfer of PhIP is of great concern.

Detection of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in the Milk of Healthy Women

“…PhIP must be transferred across the ductal mammary epithelial cells into the milk. The transfer of radiolabeled PhIP into milk has been demonstrated in mice and rats ( − ). Female offspring of rats exposed to PhIP only during the gestation and lactation period showed a higher incidence of mammary carcinomas than controls with no such exposure ().…”

Food Browning and Its Prevention: An Overview

“…PhIP injected in lactating rats can undergo a dosedependent transfer to the milk (Brittebo et al, 1994;Ja ¨gerstad et al, 1994). This finding implies that exposure of pregnant women to PhIP might also give rise to a significant exposure in the newborn and that milk could be used to monitor risk assessment of PhIP consumption by humans.…”

Hplc/Electrospray Ionization Mass Spectrometric Analysis of the Heterocyclic Aromatic Amine Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Human Milk

“…Following the systemic administration of PhIP to nursing mice or rat dams, the compound is secreted into milk and absorbed by the pups (25,26). Oral dosing of lactating rat dams with levels of PhIP comparable to human dietary exposures, 50-1000 ng per kg, resulted in PhIP milk levels on the order of 100 pg per mL (100 ppt), as measured by accelerator mass spectrometry (26).…”