Baby Blood Lead Level Elevated From Packaged Food
LEAD (EVALUATION OF HEALTH RISK TO INFANTS AND CHILDREN) EXPLANATION Lead was previously evaluated at the sixteenth meeting of the Joint FAO/WHO Expert Committee on Food Additives (Annex 1, reference 30). The Committee established a provisional tolerable weekly intake of 3 mg of lead/person, equivalent to 0.05 mg/kg b.w. for adults. This level does not apply to infants and children. The provisional weekly tolerable intake established by JECFA at that time related to all sources of exposure to lead. The Committee indicated that any increase in the amount of lead derived from drinking water or inhaled from the atmosphere will reduce the amount that can be tolerated in food. A toxicological monograph was published (Annex 1, reference 31). Two other publications of WHO have dealt with effects of lead on human health (WHO, 1973; WHO, 1977). These publications did not deal specifically with the health risks for infants and children. However, JECFA and the other WHO committees recognize that children should be considered a high-risk group in relation to lead exposure. JECFA at its twenty-first meeting (Annex 1, reference 44) discussed the problem of exposure of infants and children to contaminants in foods. The IPCS (International Program on Chemical Safety) and CEC (Commission of the European Communities), recognizing the need for a special approach to evaluating the health risks from chemicals during infancy and early childhood, have recommended principles for evaluating these risks (WHO, 1986). The basis of the special concern for infants and children relates to certain structural, functional, and behavioural differences between infants and young children and adults, in particular, the higher metabolic rate and therefore higher oxygen consumption and air intake per unit body weight in the young, the large surface area to weight ratio, the rapid body growth, different body composition, immaturity of the kidney, liver, nervous system, and immune system, and the rapid growth and development of organs and tissues such as bone and brain. The higher energy requirements of infants and children and the higher fluid, air, and food intake per unit body weight place them in a special position with regard to intake of chemicals from air, water and food. The absorption and retention of a number of metals appear to be greater in the young than in adults, and there are differences in the distribution, biotransformation, and excretion of chemicals in infants, children, and adults. Additionally, the dependence of young infants on milk or infant formula as their sole source of nutrition may raise special problems. Particular behavioural characteristics of children, such as heightened hand to mouth activity, may place them at particular risk from environmental contaminants. The nutritional and health status of the young may also modify their response to chemical contaminants and the social and cultural attitudes to child rearing may influence the degree of exposure to chemicals. EXPOSURE AND INTAKE Sources of exposure It is important to identify sources of exposure, particularly those that may be of significance to infants and children. This will provide information for developing strategies for control of exposure, if needed. Although lead is ubiquitous in the environment of industrialized nations, the contribution of natural sources of lead to concentrations in the environment is low compared to the contribution from human activities (Patterson, 1965). Through human activities such as mining, smelting, refining, manufacturing, and recycling, lead finds its way into the air, water, and surface soil. Lead-containing manufactured products (gasoline, paint, printing inks, lead water pipes, lead-glazed pottery, lead-soldered cans, battery casings, etc.) also contribute to the lead burden. Lead in contaminated soil and dust can find its way into the food and water supply. Food, drinking water, and air Lead in foods may be derived from the environment in which the food is grown or from food processing. Agricultural crops grown near heavily travelled roads or industrial sources of lead can have significant concentrations because of airborn lead deposited on them or in the soil. Canned foods are a source of lead which is leached from the solder in the seams of the cans. However, exposure from this source can be reduced by the use of seamless cans. Among cases of lead poisoning cited in the literature, lead from ceramic glazed storage vessels, leached out by acid foods, is the most frequently-reported source of high lead concentrations in foods (Mahaffey, 1983). The major source of lead contamination of drinking water is the distribution system itself. Where lead water pipes or lead-lined cisterns are used, lead may contaminate the water supply and contribute to increased blood levels in children who consume the water (Elias, 1985). Water used to prepare infant formula is always a significant source of lead for infants if it contains high lead levels (Sherlock & Quinn, 1986). The atmospheric levels of lead depend on geographical location, with major differences in lead in the atmosphere in urban and remote areas of the world. The highest concentrations are observed near sources of lead such as smelters. Levels range from 0.000076 �g/m3 in remote areas to up to 10 �g/m3 in areas near smelters (Elias, 1985). The domestic environment The domestic environment, in which infants and children spend the greater part of their time, is of particular importance as a source of lead intake. In addition to exposure from general environmental sources, some infants and young children, as a result of normal, typical behaviour, can receive high doses of lead through mouthing or swallowing of non-food items. Pica, the habitual ingestion of non-food substances, which occurs among many young children, has frequently been implicated in the etiology of lead toxicity. Soil and dust in and about the home The extent of the contribution of inhaled airborne lead to the lead burden of children is probably small. However, lead-containing particles that deposit from the air can be responsible for high concentrations of lead in dust that children ingest (Charney, 1982). A study of urban and suburban infants (USA) followed from birth to 2 years of age found that the average blood lead levels highly correlated with amounts of lead in indoor dust, top soil, and paint in their immediate environment (Rabinowitz et al., 1984). Children living near high-level sources of lead such as smelters are at high risk from lead poisoning (Landrigen et al., 1976). Exhaust from vehicles using leaded gasoline is a common source of atmospheric lead which contributes to the lead content of dust. Data from the United States Second National Health and Nutrition Examination Survey (NHANES II) indicate that leaded gasoline is a more significant source of lead than previously thought. Annest et al. (1983), using data from this study, correlated major reductions in the amounts of lead added to gasoline sold in the United States with significant reductions in children's blood lead levels. A similar relationship between leaded gasoline sales and umbilical cord blood lead levels was shown by Rabinowitz and Needleman (1983). However, other studies have indicated that the influence of lead from gasoline on blood lead levels may be relatively low (Quinn, 1985). In general, lead in soil and dust appears to be responsible for blood lead levels in children increasing above background levels when the concentration in the soil or dust exceeds 500-1,000 ppm (Milar & Mushak, 1982). Lead-based paint in the home Lead-based paint in the home has been and continues to be the major source of high-dose lead exposure and symptomatic lead poisoning for children, in spite of the fact that the use of lead in interior paints has been restricted in some countries for many years (Lin-Fu, 1982). In the past, some interior paints contained 20-30% lead and these paints remain in many older homes. Overt lead poisoning, when it occurs, is usually seen in children under 6 years of age who live in deteriorated older housing. Indirect occupational exposure in the home Lead dust that clings to the skin, hair, and clothing of workers can be carried from the workplace to the home. In one study (Baker et al., 1977) it was shown that when a parent worked with lead, the amount of lead in the blood of children correlated with the concentration of lead in dust in their homes. Children have been poisoned by lead-bearing dust brought home on parents' work clothing (Chisolm, 1982). Intake Children are more vulnerable to exposure to lead than adults because of metabolic and behavioural differences. The degree to which individual sources of lead contribute to the intake of lead by infants and children varies according to its availability in particular environmental circumstances. While lead in air, food, and water generally is at lower levels than lead in paint, soil, and dust, the former contribute to the background or baseline level which determines how much extra lead is needed from other sources before toxicity ensues. It has been estimated that in the United States, an average two-year old child may receive 44% of his daily lead intake from dust, 40% from food, 14.6% from water and beverages, and 1% from inhaled air (Elias, 1985). Detailed reviews of intake of lead are available (WHO, 1977; Elias, 1985; FAO, 1986a). Food Among children the higher food intake relative to size and the higher metabolic levels and greater motor activity compared to adults leads to higher dietary lead consumption (Mahaffey, 1985). Reported intakes of lead from food are quite variable (WHO, 1977). However, developing a reasonable estimate of lead in the diet is a continuing problem because of (1) methodological weaknesses in the accurate analysis for lead in foods and (2) the need for good dietary survey data. Beloian (1985) has proposed a mathematical model for estimating daily intake. A detailed report of dietary intake of lead by infants and children has been compiled by FAO (1986a). There has been a considerable reduction in dietary intake of lead in infants in the 0-5 month age group since the 1970s, probably due to improvements in packaging and handling of foods during processing and to reduction in lead solder in cans used for milk and infant food. Air Inhaled lead contributes little to the background body burden compared to intake from food, water, beverages, and dust. Airborne lead, however, represents an important source of lead exposure in children when deposited in dust and dirt. However, different studies reach widely different assessments of the contribution of air lead to food lead and hence body burden (Royal Commission on Environmental Pollution, 1983). Dust Dust contributes a greater proportion of lead to the background body burden of young children than to adults and older children because of their greater proclivity for ingesting dust due to their greater hand-to-mouth activity. It has been calculated that dust contributes only 7 to 11% of the baseline lead in adults, but 44% in 2-year old children (Elias, 1985). Indices of exposure For practical reasons, lead exposure in infants and children is based primarily upon measurements of lead in the blood, sometimes supplemented by measurement of lead in urine, particularly after treatment with chelating agents. These measurements correlate imperfectly with lead levels in the tissue or organ where the toxic effect may be observed. Furthermore, blood lead levels reflect only recent exposure to lead, not long-term exposure. Other methods to determine total body burden involve measurement of lead in hair, bone, or teeth (Goyer, 1982). The use of the lead content of teeth as an index of lead exposure in the general population has been considered an important advance, particularly in the investigations of the neuropsychological effects of ordinary levels of lead in the environment, since this reflects lead exposure over the child's lifetime, not merely recent exposure. However, considerable variations may occur in tooth lead concentrations in different teeth from the same child, especially when teeth are different types or from upper and lower jaws. Also, there is a marked variation of lead concentration throughout the tooth (Delves et al., 1982; Smith et al., 1983). Because of these variations, there is always a need to make suitable adjustments when using teeth for assessing lead body burden. The haematopoietic system is considered by many to be the most reliable and sensitive indicator of lead toxicity. The clinical endpoint is anaemia, which apparently occurs at lower blood lead levels in children that in adults (Goyer, 1982). The elevation of erythrocyte protoporphyrin (EP) has been well studied and can be reliably measured (U.S. CDC, 1985). Among the biologic markers of lead toxicity, this method has been the most useful in screening programs because its measurement is not susceptible to error from lead contamination and the test can be performed on capillary blood. However, correlation with blood lead at levels below 30 �g/dl is poor, and there is a rather high proportion of false negative results (Meredith et al., 1979; Bush et al., 1982). High EP values in the absence of elevated blood lead levels may indicate iron deficiency (Piomelli, 1977). Blood lead levels in children In general, blood lead levels of children up to 6-7 years of age are higher than those of non-occupationally exposed adults. Blood lead levels are highest in children aged 2-3 years, but they decrease again in children aged 6-7 years. There are no significant differences in blood lead levels between males and females less than 7 years of age. However, males in the 7+ age group generally have higher blood lead levels than females. In the United States NHANES II found that the mean blood lead concentration among children under 6 years of age was about 16 �g/dl, with mean values in about 5% of the population equal to or greater than 30 �g/dl. After the age of 5, mean blood levels declined until age 17. Mean blood levels of adult females remained lower, but blood levels in adult males were similar to those of younger children (Mahaffey, 1985). A similar pattern of distribution of blood lead levels with age in children and infants was reported in the U.K. and European Economic Community (EEC) Blood Lead Survey, 1979-1981 (Quinn, 1985), with average blood lead concentrations in the range 9-11.5 �g/dl. In addition, these studies reported the effect of geographical, environmental and personal factors on the average blood lead concentrations (Pollution Report No. 18, 1983). Blood lead levels of concern in screening programmes The U.S. Centers for Disease Control (U.S. CDC) has lowered its definition of an elevated blood lead level from 30 to 25 �g/dl. Lead toxicity is defined as an elevated blood level with an EP level in whole blood of 35 �g/dl or greater (U.S. CDC, 1985). The U.S. CDC has also described a system for grading the severity of lead toxicity using two distinct scales, one for use in screening and the other for use in clinical management. For example, at a blood level of 25 �g/dl or less and an EP of 35 �g/dl or more, the U.S. CDC recommends that children be retested, with additional assessment of iron studies. Also, in terms of clinical management, the U.S. CDC points out that the first priority is for environmental investigation and intervention and the single most important factor is to reduce exposure to lead. The EEC directive on the biological screening of the population and specific groups in the population indicated certain reference levels for each survey. The reference levels are as follows: no more than 50% should be above 20 �g/100 ml, no more than 10% above 30 �g/100 ml, and no more than 2% above 35 �g/100 ml. It was also recommended that if these levels were exceeded, action should be taken to trace and reduce the source of exposure. Follow-up investigations should be carried out in individuals over 30 �g/100 ml (EEC, 1977). In the U.K. it has been recommended that when a blood level over 25 �g/100 ml has been confirmed in a person (particularly a child), action should be taken to investigate the individual's environment and steps should be taken to reduce lead exposure (Department of the Environment and the Welsh Office, 1982). BIOLOGICAL DATA Biochemical aspects Absorption and retention The main route of lead absorption in infants and children is the gastrointestinal tract. Children absorb lead with greater efficiency than do adults. It has been estimated that 40-50% of dietary lead is absorbed in children, whereas in adults normally 5-10% of dietary lead is absorbed from the gastrointestinal tract. However, absorption in adults shows considerable variation depending on whether the lead is present in food or water or if the lead is ingested between meals. Decreased intake of essential metals such as iron, zinc, and calcium as well as poor nutritional status increase lead absorption (Rosen, 1985). In experimental animals there is some evidence that milk may promote lead absorption (Stephens & Waldron, 1975). The estimated gastrointestinal absorption rate of lead from soil and dust has been reported to be somewhat lower than from food, approximately 30% (Lepow et al., 1975). In a study by Zeigler et al. (1978) faecal excretion of lead in infants generally exceeded intake when the dietary intake of lead was less than 4 �g/kg/day. When intake of dietary lead exceeded 5 �g/kg/day, net absorption averaged 42% of intake, and retention averaged 32% of intake. Absorption and retention of lead expressed as a percentage of intake increased significantly with increasing lead intake. Absorption may be higher when nutrition is not optimal. Correlation between blood lead levels and exposure In a study with infants Ryu et al. (1983) demonstrated that with low non-dietary exposure to lead, a mean intake of 3-4 �g lead/kg b.w. was not associated with an increase in blood lead concentration. However, increased blood lead levels did occur when the dietary intakes of lead were 8-9 �g/kg b.w./day. The Glasgow duplicate diet study (Sherlock & Quinn, 1986) reported a significant correlation between dietary lead intake and blood lead concentrations of 13-week old infants. The study involved a wide range of lead intakes (40 �g to over 3000 �g/week). The high levels of lead in the diet were derived from water used to prepare the diet. The blood lead concentrations appeared to have a "non-linear" (cube root) relationship between water lead concentrations and dietary intakes of lead, with the greatest increment in blood lead levels occurring at the lower range of exposure. Lead intake from air is relatively greater in children than in adults. In adults without prolonged previous exposure to lead, each 1 �g/m3 increase in ambient air lead increases the mean blood level by approximately 1 �g/dl, while in children each 1 �g/m3 increase in ambient air lead exposure causes a mean increase of 2 �g/dl or more in the blood lead level (US EPA, 1977). Distribution and excretion A single dose of lead, orally ingested or inhaled, distributes to the various organs and systems in the body in relation to the rate of blood delivery and then redistributes in proportion to affinity of particular tissues for lead. The concentration of lead in blood reflects the overall balance between uptake and excretion and the equilibrium of exchange to and from soft and hard tissues. Lead is not uniformly distributed in the body but is apportioned among several physiologically-distinct compartments which differ in size and accessibility to lead (Rabinowitz et al., 1976; Rabinowitz et al., 1977). The blood and some components of soft tissue in rapid exchange with blood contain about 1% of the body lead, of which 90 to 99% is associated with the red blood cells. This accessible fraction correlates most closely with recent environmental exposure and to most toxic effects. Lead in this accessible portion has a mean half-life of about 36 days. Lead in other soft tissue has a mean half-life of about 40 days; this compartment is slightly smaller than the blood compartment. The lead in bone and teeth has a long half-life, about 10,000 days, and forms the largest and least accessible depot. There is variation in the amount of lead stored in various skeletal regions and in its accessibility (Rabinowitz et al., 1976). Animal experiments show that the tissue distribution of lead in the young and in adults differs. In the rat, a greater percent of the dose accumulates in the immature brain than in the adult brain. In fact, young animals retain a greater percentage of lead in all organs than do adults, even when the exposure of young and adults is the same on a �g lead/kg b.w. basis. When the blood lead level concentration in rats is plotted against tissue lead levels, the slope of the regression line for the young is greater than that for adults, indicating that tissue lead levels rise faster than blood lead levels in the young animal (Mahaffey, 1983). Man excretes lead primarily by way of the kidneys (76%) and to a lesser extent via the gastrointestinal tract (16%) and through the sweat, bile, hair, and nails (8%) (WHO, 1977). Lead accumulates in bone due to an inherent affinity for osseus tissue and only slowly returns to the blood. The longer the period of exposure to lead, the slower the rate of removal from the body (Hammond, 1982). Although animal studies suggest that lead is excreted more slowly in the young than in the adult (Hammond, 1982), metabolic balance studies in normal infants suggest that infants and young children not only absorb lead more efficiently but also excrete it more rapidly than do adults (Rabinowitz et al., 1976). Transplacental transport of lead and lead in maternal milk Lead in fetal tissues has been detected by the twelfth week of gestation (Barltrop, 1972) with highest concentrations in bone, kidney, and liver, followed by blood, brain, and heart. Cord blood contains concentrations of lead that correlate with maternal levels. Lead appears in mothers' milk, but breast milk contains only about one-tenth of the maternal blood lead concentrations (Moore, 1983). Lead toxicity Lead impairment of normal metabolic pathways The biochemical basis for lead toxicity is its ability to bind the biologically-important molecules, thereby interfering with their function by a number of mechanisms. Lead may compete with essential metallic cations for binding sites, inhibiting enzyme activity, or altering the transport of essential cations such as calcium. At the subcellular level, the mitochondrion appears to be the main target organelle for toxic effects of lead in many tissues. Lead has been shown to selectively accumulate in the mitochondria and there is evidence that it causes structural injury to these organelles and impairs basic cellular energetics and other mitochondrial functions (Brierley, 1977; Holtzman et al., 1978). Lead has been reported to impair normal metabolic pathways in children at very low blood levels (Farfel, 1985). At least three enzymes of the haeme biosynthetic pathway are affected by lead and at high blood lead levels the decreased haeme synthesis which results leads to decreased synthesis of haemoglobin. (Haeme is also a prosthetic group of a number of tissue heme proteins such as myoglobin, the P450 component of the mixed function oxidases, and the cytochromes.) Blood lead levels as low as 10 �g/dl have been shown to interfere with one of the enzymes of the haeme pathway, delta- amino-levulinic acid dehydrase (Hernberg & Nikkanen, 1970). No threshold for this effect has been established. Alterations in the activity of the enzymes of the heme synthetic pathway lead to accumulation of the intermediates of the pathway. There is some evidence that accumulation of one of the intermediates, delta- amino-levulinic acid, exerts toxic effects on neural tissues through interference with the activity of the neurotransmitter gamma-amino-butyric acid (GABA) (Silbergeld & Lamon, 1980). The reduction in heme production per se has also been reported to adversely affect nervous tissue by reducing the activity of tryptophan pyrollase, a heme-requiring enzyme. This results in greater metabolism of tryptophan via a second pathway which produces high blood and brain levels of the neurotransmitter serotonin (Litman & Correia, 1983). Red cell pyrimidine-5'-nucleotidase activity in children is inhibited at blood lead concentrations of 10-15 �g/dl and no threshold was found even below these levels (Angle et al., 1982). Lead interferes with vitamin D metabolism, since it inhibits hydroxylation of 25-hydroxy-vitamin D to produce the active form of vitamin D. The effect has been reported in children at blood levels as low as 10-15 �g/dl (Mahaffey et al., 1982). Rosen (1985) and Moore & Goldberg (1985) have published detailed reviews of the metabolic and cellular effects of lead. Target organs and systems Lead is a cumulative poison. It produces a continuum of effects, primarily on the haematopoietic system, the nervous system, and the kidneys. Haematopoietic system Excessive lead exposure in pediatric groups results in a microcytic, hypochromic, mildly haemolytic anemia. Increased blood concentrations and urinary excretion of the metabolic precursers of haeme, such as protoporphyrins and 6-amino-levulinic acid, occur before the development of overt anaemia. Blood lead concentrations in children in excess of 40 �g/100 ml have been associated with an increased incidence of anaemia (WHO, 1977). Measurements of the inhibitory effects of lead on haeme synthesis have been widely used in screening tests to determine whether medical treatment for lead toxicity is needed for children in high-risk populations who have not yet developed overt symptoms of lead poisoning. Piomelli (1980) has reported that an increase of erythrocyte protoporphyrin could be measured at blood lead levels of 14-17 �g/dl in children and Cavelleri et al. (1981) found an increase at blood lead levels between 10 and 20 �g/dl, suggesting that the erythrocyte protoporphyrin "no response" level is lower than 10 �g/dl in children. Specific changes relating to the haematopoietic system have been reported to occur at the following blood lead concentrations in children: 5 - 10 �g/100 ml 40% inhibition of erythrocyte delta-amino-levulinic acid dehydratase 10 - 25 �g/100 ml increased erythrocyte protoporphyrins 20 - 25 �g/100 ml 70% inhibition of delta-amino-levulinic acid dehydratase 30 - 40 �g/100 ml increased urinary excretion of delta-amino-levulinic acid (above 5 mg/l) 40 - 50 �g/100 ml decreased haemoglobin level The biological significance of the effects noted below 40 �g/100 ml are not known, since the degree of impairment is not sufficiently large to be reflected as a decrease in haemoglobin or haem synthesis. However there is general agreement that at levels greater than 40 �g/100 ml, lead exerts a significant effect on the haematopoietic system. The haematological changes associated with lead are considered reversible. Effects on the nervous system Lead causes a continuum of nervous system effects in children ranging from slowed nerve conduction (Landrigan et al., 1976), behavioural changes (David et al., 1972; de la Burde et al., 1975; Landrigan et al., 1975; Winneke et al., 1982, 1983), and possible small decrements in cognitive ability at about 30-60 �g lead/dl blood, to mental retardation (80 �g/dl) and acute encephalopathy and death (80-100 �g/dl) (Needleman et al., 1979; Needleman & Landrigan, 1981; Needleman, 1983). Encephalopathy and other effects on the nervous system develop in children at lower blood lead levels than in adults. Effects on the central nervous system are principally responsible for the morbidity and mortality due to lead poisoning (Mahaffey, 1977). Chelation therapy and earlier detection of lead toxicity have led to a marked decline in death from lead poisoning since the 1950s, but residual impairment of CNS function due to lead toxicity continues to occur, even in children treated with chelation therapy. Sequalae can include mental retardation, seizures, cerebral palsy, and optic atrophy. In studies with experimental animals, perinatal lead exposure delayed normal brain development in offspring and was associated with blood lead levels from 25-89 �g/dl (Reiter, 1982). Indications of peripheral nerve dysfunction, as indicated by slowed nerve conduction velocities, have been shown in children at blood lead levels as low as 30 �g/dl (Landrigan et al., 1975). The neuropsychological effects of low-level lead exposure, below that causing overt toxic effects, represent a subject of increasing interest and of continuing controversy. The concern relates to the possibility that early asymptomatic environmental lead exposure results in adverse effects on I.Q., perception, and fine motor skills of children. In the past 12-15 years, both clinical studies of children and animal research have provided information which bears on the problem of CNS effects at low-level lead exposure. Data needed to define dose-response relationships in children come principally from retrospective epidemiological studies. These have the well-known methodological problems of controlling for confounding covariants, of selection bias, of obtaining sufficiently-large population samples to achieve statistical significance, and of appropriate statistical analysis. In the case of lead there is also the problem of the shortcomings of assessing the body lead burden by the most widely used and practical method, which is measurement of blood lead levels, and the difficulties with clinical measurements of neuropsychological function. The interpretation of statistical associations between raised lead levels and psychological impairment raises another question, that of the biological mechanism by which low-level lead exposure could cause the psychological damage. Observations in animals Animal studies are available that provide information on the effects of neonatal low-level lead exposure on locomoter scheduled-controlled behaviour (Brown, 1975; Bushnell & Bowham, 1979; Rice, 1984). Other studies provide suggestions as to the biological mechanisms that may underlie the neurophysiological or neuro-psychological effects of low-level lead exposure. In one recent study, cynomolgus monkeys were dosed from birth with 0, 50, or 100 �g/kg/day of lead, resulting in steady-state blood lead levels of 3, 11, or 13 �g/dl, respectively. At 3 years of age, the monkeys were tested on an intermittent schedule for the usual measures of differential reinforcement of low rate (DRL). The performance of treated monkeys did not improve as rapidly as controls, and the treated monkeys showed greater between-session variabilities during terminal sessions. These results suggest that blood lead levels comparable to those generally found in the human population may produce neurophysiological effects (Rice & Gilbert, 1985). Other studies with experimental animals have shown that lead (a) inhibits haeme biosynthesis at lead levels below 20-30 �g/dl blood, with subsequent neurotoxic effects of 6-amino-levulinic acid or one of its metabolites, (b) interferes with the neuronal system that is responsive to acetylcholine, catecholamines, and GABA (Sibergeld & Lamon, 1980), and (c) affects intraneuronal haeme biosynthesis (Rice & Gilbert, 1985). Neuropsychological effects of lead in children Rutter (1980), Yule & Rutter (1983), DHSS (1980), Needleman (1980), and MRC (1986) have published reviews of studies on the neuropsychological effects of lead in on-overtly intoxicated children. Several categories of studies have been reviewed, including (1) clinical studies of children thought to be at risk because of high blood levels, (2) studies of children from general pediatric populations, (3) studies of children living close to lead-emitting smelters, (4) studies of mentally-retarded or behaviourally-deviant children, and (5) chelation studies. Studies prior to 1980 suggested that lead could cause psychological impairment (lower IQ and behavioural deviance) at levels below those associated with overt clinical signs of toxicity. However, most of these studies were carried out with children with blood levels in the range 40-70 �g/dl. There was little evidence that adverse neurophysiological effects could occur at much lower blood lead levels. For the studies to be applicable to the general population, studies should be carried out with children with blood lead levels below 35 �g/dl, since the median blood level of the population in nine Member States of the CEC is 13 �g/dl, with about 2% exceeding the critical level of 30 �g/dl. Similar blood lead levels have been reported in the U.S. In addition, a number of major methodological issues have been identified. These include selection of children, neuropsychological measurements, estimates of body lead levels, and adequate statistical analysis to control the effects of possible confounding variables. Since 1979 a number of studies which have attempted to correct these design deficiencies have been reported. Studies by Needleman and his colleagues (Needleman et al., 1979; Needleman, 1983) using deciduous teeth of first and second grade school children (estimated age 5.5-7.5 years) indicated a small but possible effect of lead on several measurements of neuropsychological performance, as well as reducing the IQ by 1-5 points at tooth lead levels above 20 ppm (indicative of a level of exposure). The mean blood lead level of the children was about 30 �g/dl. Similar findings were reported in other studies using tooth lead as an indicator of exposure in Germany (Winneke et al., 1982, 1983) and in the U.K. (Smith et al., 1983). In another series of studies, groups of children with blood lead levels ranging between less than 10 to 14 �g/ml or greater than 15 �g/100 ml were studied. These studies also included groups from various socio-economic backgrounds. Although one study indicated an association between full-scale I.Q. and blood lead levels, a number of confounding factors, e.g. lack of information on socio-economic background and parental I.Q., made interpretation of the study difficult (Yule et al., 1981). However, in another study corrected for these factors, no significant association between blood lead levels and various neuropsychological tests was observed (Yule & Landsdown, 1983; Yule et al., 1984). The general conclusions relating to these and other studies have been summarized by Yule & Rutter (1983) and MRC (1986). Briefly, they indicate that because of the complexity of the situation, it is impossible from the available evidence to come to a definitive conclusion on the neurophysiological effect of "ordinary" levels of lead exposure. However, the possible neurophysiological effects of lead within the range in the ordinary environment without special risks (absence of excessive sources of environmental lead), are at most small. Electrophysiological studies on children with high and low lead levels, (teeth or blood) have also been carried out. However, the significance of the variations in EEGs is not understood. Effects of lead on the kidney The kidney is the major pathway for lead excretion and is directly subject to effects of lead toxicity that may lead to impairment of its multiple functions. The early or reversible effects of lead toxicity result in proximal renal tubular dysfunction, evidenced by increased urinary excretion of glucose, amino acids, and phosphate. These effects have been reported in children with relatively high blood levels of 150 �g/dl (NAS, 1972). Chronic or irreversible lead nephropathy is characterized by intense interstitial fibrosis and tubular atrophy and dilation and results from prolonged exposure to high levels of lead. Effects on growth A recent analysis of 2695 children 7 years of age or younger, based on U.S. survey data (NHANES II), indicated that blood lead levels were a statistically-significant predictor of children's height, weight, and chest circumference. The strongest relationship was between blood lead and height, with no evident threshold found for the relationship down to the lowest observed blood lead level of 4 �g/dl (Schwarz et al., 1986). However, other factors need to be considered in the evaluation of these results, e.g. social factors. Available information on tolerable levels of lead intake for infants and young children Estimates of tolerable exposure to lead have been based on the maximum intake from all sources that would preclude accumulation of lead. The data used include (a) levels of lead in the blood of non-exposed and exposed individuals and of those with frank lead poisoning, (b) the results of experimental lead ingestion by adults, (c) measurements of faecal output of lead in exposed and non-exposed children, (d) the initial effects of increased lead ingestion, (e) rates of increase in levels of lead in the blood of exposed children, and (f) sequelae of lead poisoning. Based on the available data the U.S. Public Health Service established a daily permissible lead intake from all sources for children of 300 �g/day, which has been considered a reference base in developing measures for prevention of lead poisoning in children (DHEW, 1970; King, 1971). At the time this standard was established, 40 �g/dl of whole blood was considered evidence of undue absorption of lead; it was assumed that (1) 90% of the ingested lead was excreted and (2) total lead ingestion of 600 �g/day of lead for an adult or an estimated equivalent dose for a child 2 to 3 years old, i.e. 300 �g/day, would not result in increased blood lead levels. In 1972, Barltrop estimated the permissible limits of intake for children of different ages from birth to 15 years by scaling down from the level which was not known to cause toxicity in adults. Since he considered the surface area of the body rather than body weight to be the major variable in determining metabolic activity, he calculated the acceptable daily intake, based on the WHO adult tolerable intake of 600 �g/day (340 �g/square meter), corrected for the caloric intake of children, and determined the permissible daily intake to be 72 �g per square meter of body surface for a newborn and 298 �g per square meter for a three-year old (Barltrop, 1972). When this value was adjusted for varying body size of infants between birth and three years of age, and when the newer information on the increased absorption of lead in infants compared to that of adults was taken into account, Mahaffey recommended that the maximum tolerable intake for lead from all sources for infants between birth and age 6 months should be as low as possible and less than 100 �g/day, and that intake should be no more than 150 �g of lead/day for children between 6 months and 2 years (Mahaffey, 1977). In 1983, Ryu measured the relationship between dietary lead intake and blood lead concentration in infants from birth to 6.4 months and showed that intakes of as little as 61 �g/day resulted in increased blood levels of lead, an indication of lead accumulation. The metabolic balance studies reported by Ziegler et al. (1978) demonstrated that faecal excretion of lead generally exceeded intake when dietary intake of lead was less than 4 �g/kg/day. The study by Ryu et al. (1983) showed that with low non-dietary exposure to lead, a mean dietary intake of 3-4 �g/kg/day is not associated with an increase in blood lead concentration. Thus, the authors concluded that it seems reasonable to set the daily permissible intake for lead from all sources closer to 3 than to 8 �g/kg/day, for infants. In addition, based on their observations in the Glasgow duplicate diet study, Sherlock & Quinn (1986) have developed an equation whereby they calculate that infants having a lead intake of 680 �g/week (about 100 �g/day) will have an average blood lead level of 25 �g/dl. This blood level is now considered to be one requiring intervention to determine and reduce sources of exposure. The calculations of DHEW, of Baltrop and of Mahaffey, were based on extrapolations from data obtained from adults while those of Ryu and Sherlock & Quinn were based on measured lead intake and blood lead levels in children and therefore should be more reliable. Furthermore, at the time the earlier calculations were made, the level of blood lead considered to be indicative of toxicity in children was considerably higher than the current level. Comments Because of special concern for them, the present Committee evaluated the health risks of lead to infants and children. The Committee noted that the previous principles governing the toxicological evaluation of metal contaminants (Annex 1, Reference 30, section 3.1), as well as the principles contained in the IPCS and CEC report (WHO, 1986) on the need for a special approach to evaluating health risks during infancy and early childhood, provide valuable guidelines for evaluating these risks. The basis of the special concern for infants and children relates to a number of factors, including higher metabolic rate, rapid body growth, different body composition, immaturity of the kidney, liver, nervous system, and immune system, and development of organs and tissues such as bone and brain. The higher energy requirements of infants and children and the higher fluid, air, and water intake per unit body weight results in a relatively greater intake of contaminants in food, compared to that of adults. In addition, particular behavioural characteristics of children such as heightened hand-to-mouth activity, as well as the ingestion of non-food items (pica), may result in significant exposure to lead from non-food sources. Social and cultural attitudes of child rearing may influence exposure to non-food sources. Because the evaluation of the health effects of lead relates to exposure from all sources, any increase in lead from non-food sources (e.g. water and air) will reduce the amount that can be tolerated from food. It is important to identify sources of exposure that may be of greater significance to infants and children than adults so that strategies for control may be developed. Detailed information on sources of exposure is available (FAO, 1986a; WHO, 1977). Sources include those from the general environment, the domestic environment, and food, air, and drinking water. Exposure in the domestic environment is a particularly important source of lead exposure for children and infants, and includes lead in indoor dust, top-soil, and paint in the immediate environment. Detailed information on levels of lead in food and total intake for infants and children is available (FAO, 1986a; WHO, 1977). There is a large amount of information on the toxic effects of lead. The information used in this evaluation has been largely derived from studies with infants and children. Children absorb lead from the diet with greater efficiency than do adults. Lead absorption for adults is normally in the range of 5-10% of dietary lead. Children with lead intakes of 5 �g/kg b.w. per day are in positive balance for lead retention. The net absorption of dietary lead at this level averages 40% of the lead intake, and the net retention has been estimated to be about 30% of intake. However, metabolic studies indicate a negative balance when lead intake is less than 4 �g/kg b.w./day. The relationship between oral lead intake and blood lead levels is non-linear, with the greatest increases in blood lead levels occurring at the lower range of exposure. EVALUATION The Committee considered the available information, including correlations between blood lead levels and specific effects, blood lead levels in children in the general population, and controlled epidemiology studies. Based on the information that a mean daily intake of 3-4 �g/kg b.w. of lead by infants and children was not associated with an increase in blood lead levels, a provisional tolerable weekly intake (PTWI) of 25 �g/kg b.w. was established. This level refers to lead from all sources. The Committee recognizes that in some situations the PTWI may be exceeded, when blood lead levels may exceed 25 �g/dl. In such circumstances investigations should be carried out to determine the major source(s) of exposure, and all possible steps should be taken to ensure that lead levels in food are as low as possible, and that contributions from other environmental sources are minimized. The following are possible strategies for achieving this: Reducing or eliminating the use of lead solder and other lead-containing materials in equipment and containers coming into contact with food during its processing and handling can reduce lead contamination of foodstuffs. Lead contamination of foods in tinplate cans with lead-soldered side-seams originates mainly from the solder used in can manufacture. Contamination of foodstuffs in soldered cans can be reduced by operating the can-making equipment in such a way as to minimize contamination of the inside of the can with solder (FAO, 1986b), replacing high-lead solder by low-lead or lead-free solder, and lacquering the cans after soldering. Other ways of reducing lead contamination of canned foods include using electro-welding or other techniques instead of soldering to manufacture the can body, using two-piece cans instead of three-piece cans, limiting the level of lead permitted in the tin used to manufacture tinplate for food cans, or replacing tinplate cans by other types of container. Some glazes used for ceramic foodware contain appreciable levels of lead. If such foodware is not fired correctly, it may release large amounts of lead to foods, especially acidic products, that come into contact with it. Contamination of foods with lead from this source can be reduced by using lead-free glazes. Foodware can be checked for levels of leachable lead using one of the standardized methods now available. Contamination of drinking water with lead from plumbing systems can be eliminated by replacing the lead in such systems with other materials. If this cannot be done, contamination of soft water (pH 4.5 - 5.5) with lead from plumbing systems can be reduced by increasing the pH of the water to about pH 8.5 by the addition of lime. In some circumstances, a major source of environmental lead pollution is tetraalkyl lead used as a petrol additive. Lead in motor vehicle exhausts increases lead exposure of infants and young children in several ways. Elevated lead levels in air result directly in increased lead exposure via inhalation. Atmospheric deposition of lead on growing crops or the use of sewage sludge contaminated with lead from highway runoff as fertiliser on agricultural land can result in increased lead levels in foodstuffs and animal fodder and thus indirectly in increased dietary exposure. This type of lead pollution can be reduced by reducing or eliminating the use of lead compounds as petrol additives. House paints used in the past sometimes contained high levels of lead and therefore it is prudent to warn the parents of young children of the serious health hazards associated with the ingestion of flakes of such paint. Similar considerations apply to the use of lead in cosmetics and toys. The discharge of lead into the environment by industry, e.g. lead ore mines and primary and secondary lead smelters, and from waste disposal may give rise to high levels of local pollution. If such pollution cannot be reduced, careful attention should be given to the problems inherent in the consumption of heavily lead-contaminated food produced in areas affected by such pollution. High lead levels from environmental sources in dust and soil can result in increased ingestion of lead by young children due to sucking of contaminated fingers and mouthing or swallowing of other non-food items contaminated with dust, Simple measures, such as teaching young children to wash their hands before eating, can help to reduce lead exposure from contaminated dust, REFERENCES Angle, C.R., McIntire, M.S., Swanson, M.S., & Stohs, S.J. (1982). Erythrocyte nucleotides in children-increased blood lead and cytidine triphosphate. Pediatr. Res., 16, 331-334. Annest, J.L., Pirkle, J.L., Makuc, D., Neese, J.W., & Bayse, D.D. (1983). Chronological trend in blood lead levels between 1976 and 1980. N. Engl. J. Med. 308, 1373-1377. Baker, E., Folland, D., Taylor, F.M., Peterson, W., Lovejoy, G., Cox, D., Housworth, J., & Landrigan, P. (1977). Lead poisoning in children of lead workers. Home contamination with industrial dust. N. Eng. J. Med., 296, 260-261. Barltrop, D. (1972). Sources and significance of environmental lead for children. International Symposium, Environmental Health Aspects of Lead, Amsterdam, CEC & EPA, 675-681. Beloian, A. (1985). Model system for use of dietary survey data to determine lead exposure from food, In; Mahaffey, K.R. (ed.), Dietary and Environmental Lead; Human Health Effects, Elsevier, Amsterdam-New York-Oxford, pp. 109-155. Brierley, G.P. (1977). Effects of heavy metals on isolated mitochondria. In: Lee, S.D., (ed.), Biochemical Effects of Environmental Pollutants. Ann Arbor Sci. Publ. Inc., Ann Arbor, pp. 397-411. Brown, D. (1975). Neonatal lead exposure in the rat; decreased learning as a function of age and blood lead concentrations. Tox. Appl. Pharmacol., 32, 628-637. Bush, B., Doran, D.R., & Jackson, K.W. (1982). Evaluation of erythrocyte protoporphyrin and zinc protoporphyrin as microscreening procedures for lead poisoning detection. Amer. Clin. Biochem., 19, (2), 71-76. Bushnell, P. & Bowman, R. (1979). Persistance of impaired reversal learning in young monkeys exposed to low levels of dietary lead. J. Tox. Environ. Health, 5, 1015-1023. Cavalleri, A., Baruffini, A., Minoia, C., & Bianco, L. (1981). Biological response of children to low levels of inorganic lead. Environ. Res., 25, 415-423. Charney, E. (1982). Lead poisoning in children: The case against household lead dust. In: Chisolm J.J. and O'Hara D.M. (ed.), Lead Absorption in Children. Urban & Schwarzenberg, Baltimore-Munich, pp. 35-42. Chisolm, J.J., Jr. (1982). Management of increased lead absorption Illustrative cases. Ibid, pp. 171-188. David, O., Clark, J., & Voeller, K. (1972). Lead and hyperactivity. The Lancet, 2, 900-903. de la Burde, B., McLin S., & Choate, M.S. (1975). Early asymptomatic lead exposure and development at school age. J. Pediatrics, 87, 638-642. Delves, T., Clayton, B., Carmichael, A., Bubear, M., & Smith, M. (1982). An appraisal of the analytical significance of tooth lead measurements as possible indices of environmental exposure of children to lead. Am. Clin. Biochem., 19, 329-337. Department of the Environment and the Welsh Office (1982). Lead in the environment (Circular 22/82), 7 September. DHEW (1970). Steinfeld, J.L., Surgeon General's policy statement on medical aspects of childhood lead poisoning. U.S. Public Health Service, Department of Health, Education, and Welfare, Washington DC, USA. DHSS (1980). Lead and health. The report of a Department of Health and Social Security Working Party on Lead in the Environment (Lawther Report). HMSO, London, U.K. EEC (1977). Council directive of 29 March on biological screening of the population for lead. (77/312/EEC): Official Journal of the European Communities, L105/10-17, 28 April. Elias, R.W. (1985). Lead exposures in the human environment. In: Mahaffey, K. (ed.), Dietary and Environmental Lead: Human Health Effects, Elsevier, Amsterdam-New York-Oxford, pp. 79107. FAO (1986a). Exposure of infants and children to lead. Food and Agriculture Organization of the United Nations, Rome (in preparation). FAO (1986b). Guidelines for can manufacturers and food canners. FAO Food and Nutrition Paper No. 36. Food and Agriculture Organization of the United Nations, Rome. Farfel, M.R. (1985). Reducing lead exposure in children. Ann. Rev. Public Health, 6, 333-360. Goyer, R.A. (1982). Lead toxicity. In: Chilsom, J.J. & O'Hara, D.M. (ed.), Lead Absorption in Children, Urban & Schwarzenberg, Baltimore-Munich, pp. 21-33. Hammond, P.B. (1982). Exposure to lead. Ibid, pp. 55-61. Hernberg, S. & Nikkanan, J. (1970). Enzyme inhibition by lead under normal urban conditions. The Lancet 1: 63-64. Holtzman, J., Hsu, S., & Mortell, P. (1978). In vitro effects of inorganic lead on isolated brain mitochondrial respiration. Neurochem. Res., 3, 195-206. King, B.G. (1971). Maximum daily intake of lead without excessive body lead-burden in children. Amer. J. Dis. Child., 122, 337-340. Landrigan, P.J., Whitworth, R.H., Baloh, R.W., & Staehling, N.W. (1975). Neuropsychological dysfunction in children with chronic low level lead absorption. The Lancet, 1, 705-712. Landrigan, P.J., Baker, E.L. Jr., Feldman, R.G., Cox, D.H., & Eden, K.V. (1976). Increased lead absorption with anemia and slowed nerve conduction in children near a lead smelter. J. Pediatr. (St. Louis), 89, 904-910. Lepow, M.L., Bruckman, L., Gillette, M., Markowitz, S., Robino, R., & Kapish, J. (1975). Investigations into sources of lead in the environment of urban children. Environ. Res., 10, 415-426. Lin-Fu, J.S. (1972). The evolution of childhood lead poisoning as a public health problem. In: Chisolm, J.J. & O'Hara, D.M. (ed.), Lead Absorption in Children, Urban & Schwarzenberg, Baltimore-Munich, pp. 1-10. Litman, D.A. & Correia, M.A. (1983). L-tryptophan; a common denominator of biochemical and neurological events of acute hepatic porpyrias? Science, 222, 1031-1033. Mahaffey, K.R. (1977). Relation betwen quantities of lead ingested and health effects of lead in humans. Pediatrics, 59, 448-456. Mahaffey, K.R. (1983). Absorption of lead by infants and young children. In: Schmidt, E.H.F. & Hildebrandt, A.G. (ed.), Health Evaluation of Heavy Metals in Infant Formula and Junior Food, Springer-Verlag, Berlin-Heidelberg-New York, pp. 69-85. Mahaffey, K.R. (1985). Factors modifying susceptibility to lead toxicity. In: Mahaffey, K.R. (ed.), Dietary and Environmental Lead: Human Health Effects, Elsevier, Amsterdam-New York-Oxford, pp. 373-419. Mahaffey, K.R., Rosen, J.F., Chesney, R.W., Peeler, J.T., Smith, C.M. & DeLuca, H.F. (1982). Association between age, blood lead concentration, and serum 1,25-dihydroxycholecalciferol levels in children. Am. J. Clin. Nutr., 35, 1327-1331. Meredith, P.A., Moore, M.R., & Goldberg, A. (1979). Erythrocyte delta-aminolevulinic acid dehydratase activity and blood protoporphyrin concentrations as indices of lead exposure and altered haem biosynthesis. Clinical Science, 56, 61-69. Milar, C.R. & Mushak, P. (1982). Lead contaminated housedust: Hazard, measurement and decontamination. In: Chisolm, J.J. & O'Hara, D.M. (ed.), Lead Absorption in Children, Urban & Schwarzenberg, Baltimore-Munich, pp. 143-152. Moore, M.J. (1983). Lead exposure and water plumbosolvency. In: Rutter M. & Jones R.R. (ed.), Lead versus Health, John Wiley and Sons Ltd., pp. 79-98. Moore, M.R. & Goldberg, A. (1985). Health implications of the haematopoietic effects of lead. In: Mahaffey, K.R. (ed.), Dietary and environmental lead: Human health effects. Elsevier Science Publishers, B.V. MRC (1986). The neurological effects of lead in children. A review of recent research, 1978-1983. Medical Research Council. NAS (1972). Lead. Airborne lead in perspective. Committee on Biologic Effects of Atmospheric Pollutants. National Academy of Sciences, Washington DC, USA. Needleman, H.L., Gunnoe, C., Leviton, A., Reed, R., & Peresie, H. (1979). Deficits in psychologic and classroom performance of children with elevated dentine lead levels. N. Eng. J. Med., 300, 689-732. Needleman, H.L. (1980) (ed.). Low Level Lead Exposure. The Clinical Implications of Current Research, Raven Press, New York. Needleman, H.L., & Landrigan, P.J. (1981). The health effects of low level exposure to lead. Ann. Rev. Public Wealth, 2, 277-298. Needleman, H.L. (1983). Low level lead exposure and neuropsychological performance. In: Rutter, M. & Jones, R.R. (ed.), Lead versus Wealth, John Wiley and Sons Ltd., pp. 229-242. Patterson, C.C. (1965). Contaminated and natural lead environment of man. Arch. Env. Health, 11, 344-363. Piomelli, S. (1977). Free erythrocyte porphyrins in the detection of undue absorption of Pb and of Fe deficiency. Clin. Chem. 23, 264-9. Piomelli, S. (1980). The effects of low-level lead exposure on heme metabolism. In: Needleman, H.L. (ed.), Low level lead exposure: The clinical implications of current research. Raven Press, pp. 67-74. Pollution Report No. 18 (1983). Dept. of the Environment, European Community Screening Programme for Lead, United Kingdom results for 1981. Quinn, M.J. (1985). Factors affecting blood lead concentrations in the U.K.. Results of the EEC Blood Lead Surveys, 1979-1981. Inter. J. Epidemiology, 14, 420-431. Rabinowitz, M.B., Wetherill, G.W., & Kopple, J.D. (1976). Kinetic analysis of lead metabolism in healthy humans. J. Clin. Invest., 58, 260-270. Rabinowitz, M.B., Wetherill, G.W., & Kopple, J.D. (1977). Magnitude of lead intake from respiration by normal men. J. Lab. Clin. Med., 90, 238-248. Rabinowitz, M.B. & Needleman, M.L. (1983). Petrol lead sales and umbilical cord blood lead levels in Boston, Massachusetts. The Lancet, 1, 63. Rabinowitz, M.B., Leviton, A., Needleman, H., Bellinger, D., & Waternauz, C. (1984). Environmental correlates of infant blood lead levels. In: 2nd Int. Conf. on Prospective Lead Studies, Cincinnati; Dept. Environ. Health, Univ. of Cin. and EPA. Reiter, L.W. (1982). Developmental neurotoxicity of lead: Experimental studies. In: Chisolm, J.J. & O'Hara, D.M. (ed.), Lead Absorption in Children, Urban & Schwarzenberg, Baltimore-Munich, pp. 43-54. Rice, D.C. (1984). Behevioural deficit (delayed matching to sample) in monkeys exposed from birth to low levels of lead. Toxicol. Appl. Pharmacol., 75, 337-345. Rice, D.C. & Gilbert (1985). Low lead exposure from birth produces behavioural toxicity (DRL) in monkeys. Toxicol. Applied Pharmacol., 80, 421-426. Rosen, J.F. (1985). Metabolic and cellular effects of lead; a guide to low level lead toxicity in children. In: Mahaffey, K.R. (ed.), Dietary and environmental lead; human health effects. Elsevier Science Publishers, Amsterdam-New York-Oxford, pp. 157-185. Royal Commission on Environmental Pollution (1983). Ninth Report, Cmnd 8852. Rutter, M. (1980). Raised lead levels and impaired cognitive/ behavioural functioning. A review of the evidence. Dev. Med. Child. Neurol., 22, Suppl. 42. Ryu, J.E., Ziegler, E.E., Nelson, S.E., & Fomon, S.J. (1983). Dietary intake of lead and blood lead concentration in early infancy. Am. J. Dis. Child., 137, 886-891. Schwarz, J., Angle, C., & Pitcher, H. (1986). The relationship between childhood blood lead and stature. Pediatrics (in press). Sherlock, J.C. & Quinn, M.J. (1986). Relationship between blood lead concentrations and dietary lead intake in infants: The Glasgow Duplicate Diet Study, 1979-1980. Food Additives and Contaminants, 3, 167-176. Silbergeld, E.K. & Lamon, J.M. (1980). Role of altered heme synthesis in lead neurotoxicity, J. Occup. Med., 22, 680-684. Smith, M., Delves, T., Lansdown, R., Clayton, B., & Graham, P. (1983). The effects of lead exposure on urban children. The Institute of Child Health, Southampton study. Develop. Med. Child. Neurology, 25, 1-54. Stephens, R. & Waldron, H.A. (1975). The influence of milk and related dietary constituents on lead metabolism. Fd. Cosmet. Toxicol., 13, 555-563. U.S. CDC (1985). Preventing lead poisoning in young children. A statement by the Centers for Disease Control, U.S. Department of Health and Human Services, Atlanta GA, USA. U.S. EPA (1977). Air quality criteria for lead, U.S. Environmental Protection Agency, Office of Research and Development (Publ. No. EPA-6-/8-77-0170), Washington DC, USA. WHO (1973). Trace elements in human nutrition. World Health Organization, Geneva, Technical Report Series No. 532. WHO (1977). Lead. Environmental Health Criteria 3. World Health Organization, Geneva. WHO (1986). Principles for evaluating health risks from chemicals during infancy and early childhood; the need for a special approach. Environmental Health Criteria 59. World Health Organization, Geneva. Winneke, G., Hrdina, K.G., & Brockhaus A. (1982). Neuropsychological studies in children with elevated tooth-lead concentrations I, Pilot study. Int. Arch. Occup. Environ. Health, 51, 169-183. Winneke, G., Kramer, U., Brockhaus, A., Ewers, U., & Jujanek, G. (1983). Neuropsychological studies in children with elevated tooth lead concentrations II, Extended study. Int. Arch. Occup. Environ. Health, 51, 231-252. Yule, W., Lansdown, R., Millar, I.B., & Urbanowicz, M.A. (1981). The relationship between blood lead concentration, intelligence, and attainment in a school population: a pilot study. Dev. Med. Child. Neurol., 23, 567-576. Yule, W. & Lansdown, R. (1983). Lead and children's development, recent findings. In: "Heavy Metals in the Environment", proceedings of an International Conference at Heidelberg, W. Germany, 6-9 Sept. 1983. Published by CEP Consultants, Edinburgh, U.K. Yule, W. & Rutter, M. (1983). Effect of lead on children's behaviour and cognitive performance; a critical review. In: Mahaffey, K.R. (ed.), Dietary and Environmental Lead: Human Health Effects, Elsevier, Amsterdam-New York-Oxford, pp. 211-259. Yule, W., Urbanowicz, M.A., Lansdown, R. & Millar, I. (1984). Teacher's ratings of children's behaviour in relation to blood lead levels. Brit. J. Dev. Psychol., 2, 295-305. Ziegler, E.E., Edwards, B.B., Jensen, R.L., Mahaffey, K.R., & Fomon, S.J. (1978). Absorption and retention of lead by infants during infancy and early childhood: The need for a special approach. Ped. Res. 12, 29-34.
See Also: Toxicological Abbreviations Lead (EHC 3, 1977) Lead (ICSC) Lead (WHO Food Additives Series 4) Lead (WHO Food Additives Series 13) Lead (WHO Food Additives Series 44) LEAD (JECFA Evaluation) Lead (UKPID)
Baby Blood Lead Level Elevated From Packaged Food
Source: https://inchem.org/documents/jecfa/jecmono/v21je16.htm
0 Response to "Baby Blood Lead Level Elevated From Packaged Food"
Post a Comment