Dose-dependent milk transfer and tissue distribution of the food mutagen PhIP in rats and their suckling pups.
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.
Department of Applied Nutrition and Food Chemistry, University of Lund, Sweden.
I M
IM
Jägerstad
M A
MA
Johansson
A A
AA
Karlsson
K I
KI
Skog
A
A
Oskarsson
I
I
Palminger-Hallén
R
R
Ivhed
E B
EB
Brittebo
D000818:Animals; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000493:pharmacokinetics*; D007774:Lactation; D008892:Milk / Q000378:metabolism*; D009153:Mutagens / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine