Susceptibility to lead

Susceptibility to lead toxicity is influenced by dietary levels of calcium, iron, phosphorus, vitamins A and D, dietary protein, and alcohol (Calabrese 1978). Low dietary ingestion of calcium or iron increased the predisposition to lead toxicity in animals (Barton et al. 1978a Carpenter 1982 Hashmi et al. 1989a Six and Goyer 1972 Waxman and Rabinowitz 1966). Iron deficiency combined with lead exposure acts synergistically to impair heme synthesis and cell metabolism (Waxman and Rabinowitz 1966). 

Nutritional surveys indicate that children of low-income groups consume less than recommended dietary allowances of calcium and iron. Dietary deficiencies of these two minerals have been shown to potentiate the toxicity of lead (Johnson and Tenuta 1979 Yip et al. 1981 Ziegler et al. 1978). Thus, nutrient deficiencies in conjunction with a developmental predisposition to absorb lead makes this subset of children at a substantially elevated risk. More information on children s susceptibility to lead is presented in Section 2.6. 

People with Neurologic Dysfunction or Kidney Disease. This population is unusually susceptible to lead exposure. The neurologic and renal systems are the primary target organs of lead intoxication, which may become overburdened at much lower threshold concentrations to elicit manifestations of lead intoxication (Benetou-Marantidou et al. 1988 Chisolm 1962, 1968 Lilis et al. 1968 Pollock and Ibels 1986). 

Mylroie AA, Moore L, Olyai B, et al. 1978. Increased susceptibility to lead toxicity in rats fed semipurified diets. Environ Res 15 57-64. 

Heavy metals stimulate or inhibit a wide variety of enzyme systems (16, 71, 72), sometimes for protracted periods (71, 73). These effects may be so sensitive as to precede overt toxicity as in the case of lead-induced inhibition of 8 ALA dehydrase activity with consequential interference of heme and porphyrin synthesis (15, 16). Urinary excretion of 8 ALA is also a sensitive indicator of lead absorption (74). Another erythrocytic enzyme, glucose-6-phosphatase, when present in abnormally low amounts, may increase susceptibility to lead intoxication (75), and for this reason, screens to detect such affected persons in lead-related injuries have been suggested (76). Biochemical bases for trace element toxicity have been described for the heavy metals (16), selenium (77), fluoride (78), and cobalt (79). Heavy metal metabolic injury, in addition to producing primary toxicity, can adversely alter drug detoxification mechanisms (80, 81), with possible secondary consequences for that portion of the population on medication. 

Hydrocarbon oxidation on base metal catalysts is also susceptible to lead poisoning, especially if the catalysts are exposed to relatively high temperatures, for at least part of their service time. It was noted above that lead retention, especially on base metal catalysts, also increases with temperature up to a certain point. This behavior is shown by the results of Yao and Kummer (81) in Fig. 18. One should note that the hydrocarbon used for testing catalyst activity, namely propylene, was quite reactive. With a less reactive test hydrocarbon one could expect a still sharper effect. The comparison with a reference production noble metal catalyst, given in Fig. 18, is quite instructive. 

Lead Exposure in Children Lead poisoning is a silent epidemic and affects all ages, including infants and children. Children are more susceptible to lead-induced toxicity. Children absorb as much as 50% of lead, compared with... 

Lead poisoning is caused by the absorption of lead through the digestive tract, lungs, or skin. Children living in older homes are especially susceptible to lead poisoning. Children eat paint chips that contain lead because the paint has a sweet taste. 

Lead poisoning is not as common in domestic poultry as in wild birds, but it is the most common toxicity reported in the avian species. Lead shot has caused losses in waterfowl populations throughout North America. All birds are susceptible to lead poisoning, but most losses are reported in waterfowl because their feeding habits predispose them to the ingestion of lead pellets from shotguns and other sources. 

Wetmur JG, Kaya AH, Plewinska M, Desnick RJ. Molecular characterization of the human aminolaevuli-nate dehydratase 2 (ALAD2) allele implications for molecular screening of individuals for genetic susceptibility to lead poisoning. Am J Hum Gen 1991 49 757-63. 

Certain genetic, medical, or nutritional conditions render a person susceptible to lead poisoning (Table 8-3). A genetic indicator of susceptibility may be polymorphism of the enzyme 8-aminolevulinic acid de-... 

As shown in Figure 15, two pathways are of course susceptible to lead to the ureido ring, the carhamoylation taking place at N-7 or N-8. After trapping experiments, which were not entirely conclusive, a NMR study established that carhamoylation takes place at N-7. When [7- N]DAPA and C02 were incubated with an excess of enzyme, only the N-7 carbamate was observed, and pulse-chase experiments showed that this carbamate was kinetically competent. ... 

On more detailed examination one can find anaemia and punctate basophilia, heightened bone density (particularly at metaphyseal zones) and raised intracranial pressure. This last will give rise to the coma and convulsions seen more frequently in children. In children the brain appears more severely affected than in adults, where characteristic features of the encephalopathy are headache, lassitude, irritability. Although the immature brain is particularly susceptible to lead, encephalopathy presents in adults... 

The vitamin D receptor (VDR) gene, located at chromosome 12cen-12 is involved in calcium absorption through the gut and into calcium-rich tissues such as bone. VDR may play a role in susceptibility to lead bioaccumulation (Schwartz etal. 2000). Most studies on the VDR gene have focused on the Bsml polymorphism, defined by the restriction enzyme Bsml (Tokita et al. 1996). This polymorphism results in three genotypes denoted bb when the restriction site is present, BB when it is absent, and Bb when both alleles are present. 

Onalaja AO and Claudio L (2000) Genetic susceptibility to lead poisoning. Environ Health Per-spect 108 23 - 28. 

Chelation Children are particularly susceptible to lead poisoning, due to their smaller body sizes and rapid rates of development. In serious cases, a process called chelation therapy might be the only way to save the child s life. Chelation therapy reverses one important effect of lead poisioning, replacing toxic lead with beneficial calcium in the body. 

Are there specific genotypes that account for increased susceptibility to lead poisoning ... 

Mice (Mus sp.) fed a zinc-deficient diet of 0.7 mg Zn/kg ration for 40 days, when compared to mice fed a zinc-adequate diet of 36.5 mg Zn/kg, had a reduced growth rate, impaired phagocytic function, increased susceptibility to lead poisoning, and reduced zinc content in blood (0.7mg/L vs. 1.0-1.1) and liver (12.0 mg Zn/kg EW vs. 17.0-19.0). Zinc deficiency during early development affects neural tube development through arrested cell... 

Children are acknowledged to be more susceptible to lead poisoning for a wide variety of reasons, which include a greater intake and hence uptake of lead from the diet and the atmosphere per unit body weight, as well as the incomplete development of metabolic pathways and the blood-brain barrier [6]. Concern is therefore, now focused on the neurobehavioural effects of lead in children, in particular on the more subtle effects, which have become widely known as sub-clinical , although this term is strictly self-contradictory. These effects consist mainly of cognitive (mental) or sensory-motor integration (coordination) deficiencies. 

---