Risk assessment in relation to neonatal metal exposure.

Rapid changes in organ development and function occur during the neonatal period. During this period the central nervous system is in a rapid growth rate and highly vulnerable to toxic effects of, e.g., lead and methylmercury. Furthermore, the kinetics of many metals is age-specific, with a higher gastrointestinal absorption, less effective renal excretion as well as a less effective blood-brain barrier in newborns compared to adults. Due to their low body weight and high food consumption per kg of body weight, the tissue levels of contaminants can reach higher levels in newborns than in adults. Generally, there is a low transfer of toxic metals through milk when maternal exposure levels are low. However, knowledge is limited about the lactational transport of metals and the potential effects of metals in the mammary gland on milk secretion and composition. There are some data from rodents on the lactational transfer and the uptake in the neonate of inorganic mercury, methylmercury, lead and cadmium. Metal levels in human breast milk and blood samples from different exposure situations can give information on the correlation between blood and milk levels. If such a relationship exists, milk levels can be used as an indicator of both maternal and neonatal exposure. Better understanding of the neonatal exposure, including kinetics in the lactating mother and in the newborn, and effects of toxic metals in different age groups is needed for the risk assessment. Interactions with nutritional factors and the great beneficial value of breast-feeding should also be considered.

Kinetic observations in neonatal mice exposed to lead via milk.

The absorption and disposition of lead in blood was examined in 10-day-old suckling mice exposed via milk. Lactating dams were administered a single intravenous injection of 0.05 mg Pb (2.5 mCi 203Pb)/kg body wt. Lead concentrations in blood of the suckling offspring were measured for 10 days after administration to the dams. Maximum blood lead concentrations in the pups were recorded between 50 and 74 hr after dams' administration despite the fact that the majority of the lead dose to the sucklings was delivered within 24 hr after dams' administration. Kinetic analysis of pups' blood lead data revealed a rate-limited absorption in the suckling pups with an absorption half-life of approximately 17 hr in the pups. This delayed absorption is most likely due to a retention of casein-bound lead in the ileal mucosa which has a high pinocytotic activity of dietary proteins in infant rodents. The present results also indicated that the distribution of lead to the peripheral tissues in the suckling mice was different than that of adults. The conflicting evidence on whether milk enhances or inhibits the absorption of lead in infant rodents may thus be explained by measurements of lead absorption at different time periods after administration to the animals. It is also suggested that the milk diet is one reason for the increased absorption of lead seen in immature rodents.

Exposure to toxic elements via breast milk.

Breast milk is the ideal nutrient for the newborn, but unfortunately also a route of excretion for some toxic substances. Very little attention has been paid to breast milk as a source of exposure to toxic elements. The dose-dependent excretion is breast milk and the uptake in the neonate of inorganic mercury, methylmercury and lead were studied in an experimental model for rats and mice. The transfer of mercury from plasma to milk was found to be higher in dams exposed to inorganic mercury than to methylmercury. In contrast, the uptake of mercury from milk was higher in the sucklings of dams exposed to methylmercury than to inorganic mercury. Pre- and postnatal exposure to methylmercury resulted in increased numbers and altered proportions of the thymocyte subpopulation and increased lymphocyte activities in the offspring of mice and also effects on the levels of noradrenaline and nerve growth factor in the developing brain of rats. Mercury in blood and breast milk in lactating women in Sweden was studied in relation to the exposure to mercury from, fish and amalgam. Low levels were found; the mean levels were 0.6 ng g-1 in milk and 2.3 ng g-1 in blood. There was a statistically significant correlation between mercury levels in blood and milk, showing that milk levels were approximately 30% of the levels in blood. Inorganic mercury exposure from amalgam was reflected in blood and milk mercury levels. Recent exposure to methylmercury from consumption of fish was reflected in mercury levels in the blood but not in milk.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Transfer of ochratoxin A from lactating rats to their offspring: a short-term study.

A dose-dependent transfer of ochratoxin A into the milk of lactating rats was found after a single oral dose of ochratoxin A, given in the dose levels of 10, 50, and 250-micrograms ochratoxin A/kg body weight by gastric intubation. The milk/blood concentration ratio of ochratoxin A at 24 and 72 h was 0.4 and 0.7, respectively. A linear relationship was found between the concentration of ochratoxin A in the dam's milk and in the blood of the pups at 72 h, as well as in the dam's milk and in the kidneys of the pups. The pup blood/milk concentration ratio of ochratoxin A was approximately 6. At 72 h the sucklings had higher levels of ochratoxin A than their dams in both blood and kidneys. The results show that the concentration of ochratoxin A in milk can be used as an indicator of the continuously administered dose to the suckling.