Respiratory ailments, learning disabilities, sore throats, hyperactivity, and attentional deficits were common to the school children. While there was little medical knowledge as to what caused these conditions, circumstantial and coincidental evidence pointed to the neurotoxins in the air and embedded in the soil where Kenthia and her classmates played.

School and health authorities downplayed the environmental significance of the children's lead poisoning and its implication for the community's children. It was assumed there was a safe dose and background level for lead and other chemical pollutants. Since the poison in the soil was invisible, the poisoning incident was soon forgotten, and no one thought anything was wrong.

This paper grows out of the concern that the still current concept of a safe dose or no-effect level, per se, for lead and other metal toxins is unacceptable. These limits where they are set are based on the premise that there is a level of toxic concentration in human blood and tissue below which neurological and intellectual functioning, motor performance and behavior, and the normal bodily processes of growth and repair are all uninfluenced by the invading material. Such a notion is inconsistent with what is now known about children's neuropsychologic response to low levels of lead and other poisonous metals.

It is to be expected that regulators, lawyers, legislators, and the public want toxicologists to tell them what are safe levels (as opposed to hazardous levels). What is unexpected is the insouciance with which toxicologists have accepted the responsibility of establishing safe levels, that is, of proving that there are no effects at or below particular levels. Everyone accepts that it is formally impossible to prove the null hypothesis, but people say that for practical purposes there are levels that one can be "virtually certain" have no effects. But it is for practical reasons, in part, that the concept of an identifiable "no effect" level is unacceptable.

First, the minimum threshold for a real effect can not be determined satisfactorily. As Dews (1994) evinced, the minimum dose of a toxin below which there is no effect is the lower asymptote of the dose-effect curve. The slope of the sigmoid dose-effect curve becomes less and less as the asymptote of the "no effect" level is approached. The lower the slope, the greater is the effect of errors, random or nonrandom in the measurement of effect on the estimates of dose. At levels where the effect has become so low as to be virtually "no-effect," the precision with which the level can be measured is also so low that the estimate is useless for practical, as well as theoretical, purposes. Second, the nature of the human organism is such that it is capable of idiosyncratic response to ecological variation and disturbancy of body chemistry. Rare occurrences are "lost" within risk calculations since the statistical methods underpinning such actuarial calculations are illequipped to deal with isolated cases.

The view that there is a background level in the environment which is safe is equally spurious. These are manmade toxins; if they are in the environment, then man has put them there. Air borne lead levels are more than two hundred times greater now than they were three thousand years ago. The amount of lead in our oceans has increased more than tenfold since ancient times. Sediment from the bottom of lakes in the United States contains an average of twenty times more lead now than it did just less than a hundred years ago. The average American has more than one hundred times as much lead in his or her blood as the average person did before smelting began. The lead content of bones is now five hundred to more than two thousand times higher (Patterson, 1965).

A plethora of studies conducted during the last two decades indicate the toxic effects of low levels of lead, cadmium, mercury, arsenic, and aluminum on development and have failed to determine no-effect thresholds. The evidence of these effects will be reviewed here in terms of (1) neuropsychologic performance of general populations, (2) mental retardations, (3) learning disabilities, and (4) behavior disorders.

General Populations

Lead is probably the most widely researched of all environmental tetragenic agents. Interest in the effect of lead on health has quite a long history. It is recognized as an environmental hazard in Victorian times and referred to in Roman times. Focused research interest on the link between environmental lead and children's development is of much more recent origin.

Needleman and Gatsonis (1990) conducted a meta-analysis of 12 modern studies of childhood exposures to lead in relation to intellectual quotient. There were seven blood and five tooth studies from various countries with sample sizes ranging from 75 to 724. The joint P values for the blood lead studies were < .0001 for two methods of statistical analysis, while in the tooth lead studies they were < .0005 and < .004. The hypothesis that lead impairs children's IQ at low dose was strongly supported by the quantitative review, and the effect was robust to the impact of any single study. Baghurst et al. (1992) in a longitudinal study of 494 Australian children living near a lead smelter observed an inverse association between blood lead concentrations and intellectual abilities at the ages of two, four, and seven years. Other toxic metals and their synergistic interactions have been investigated in relation to IQ. Marlowe (1988) in a multimetal study (N = 58) reported a strong link between exposure to mercury and the metal-metal interaction of lead with cadmium and intellectual deficit in rural Wyoming children. Hair mercury levels accounted for eight percent of the variance in the children's psychometric performance, while the interaction of hair lead and hair cadmium levels accounted for an additional 12 percent. Thatcher, Lester, McAlaster, and Horst (1982) reported a significant negative relationship between hair lead and hair cadmium levels and psychometric test scores in 149 children in rural Maryland public schools. The results of these IQ studies accord well with the view that the "no effect" threshold exists throughout the whole range of metal burdens regarded as normal in children.

General population studies have also demonstrated that academic achievement, classroom behavior, and motor performance are sensitive to low levels of lead and other metal pollutants. Part of Needleman et al.'s 1979 Boston study examined the relationships between teachers' ratings of first and second grade children on an informal 11-item classroom behavior scale and children's dentine lead levels (N = 2,146). The relationship of negative reports increased in a dose related fashion for all 11 items. Bellinger, Needleman, Hargrave, and Nichols (1981) conducted a three year followup study and measured on- and off-task behavior of a sample of these children. Utilizing applied behavior analysis, the results showed hat high lead children displayed more off-task behavior in eight behavioral categories when compared with middle lead subjects and low lead subjects. A ten year followup study of these children demonstrated that the effects of low level lead exposure persist (Needleman and Allred, 1990). When these subjects were reexamined it was found that subjects with dentine lead levels greater than 20 ppm in 1978 had markedly high risk of dropping out of school, lower class standing, greater absenteeism, and impairment of fine motor skills as compared to those subjects who had dentine lead levels less than 10 ppm in 1978.

Lansdown, Yule, Urbanowicz, and Millar (1983) in a replication of Needleman's 1979 study suggested a dose response relationship between teacher reported deviant behavior and increased blood lead levels in 166 London children who lived near lead works. Hyperactivity and conduct problems were also found to be significantly related to children's blood lead levels independent of age. Children in the top 50% of the lead distribution scored significantly lower on reading and spelling achievement. Tuthill (1992) utilizing the same measure of classroom behavior used in the 1979 Needleman and 1983 Lansdown studies discovered a striking and highly linear dose response relationship between increasing hair lead concentrations and negative teacher ratings in 277 first graders in western Massachusetts.

Winneke et al. (1982) reported negative associations between 317 German children's dentine lead levels and mother and teacher ratings of attention, endurance, and organization. Maracek et al. (1983) showed that increasing lead levels in Philadelphia's inner city black children were associated with deficits in visual-motor functioning and perceptual integration, right-left orientation, and verbal abstraction. The results suggest that levels of lead exposure common to innercity children are sufficient to produce neuropsychologic impairment.

Charles Moon and colleagues' study of 69 Wyoming school children (1985) found that the combination of lead, arsenic, cadmium, mercury, and aluminum hair concentrations and their synergistic interactions accounted for 23 percent of the variation of test scores for reading, spelling and visual-motor performance. Marlowe et al. (1985) showed that hair lead values accounted for 10 percent of the variation of 80 Wyoming children's teacher-rated nonadaptive behavior scores, and the interactions of lead with arsenic and lead with cadmium accounted for an additional seven percent. Inverse relationships between hair aluminum values and children's fine and gross motor performance have also been reported (Marlowe, 1992).

The effects of maternal metal levels and related foetal metal levels have been less well documented than studies concerned with educational attainment and behavior of the developing child. Nevertheless, as Waldron (1980) noted, "What may be of importance to the development of neuropsychiatric abnormalities is the degree to which children are exposed at the time of maximum brain development, which includes exposure in utero." Lead as Barltrop (1969) pointed out is readily transferred across the human placenta and can be found in foetal tissue. Wibberly et al. (1977) reported pronounced mean elevations of lead in placenta from still and malformed births. Bryce-Smith, Deshpande, Hughes, and Waldron (1977) found that the mean lead and cadmium levels in the bones of still and malformed births was five to ten times greater than normal. Moreover, Moore, Meredith, and Goldberg (1977) showed that early post natal blood lead elevations were significantly associated with an increased risk of mental retardation subsequently. Two prospective studies have found that the lead concentration in the umbilical cord blood is predictive of developmental progress in childhood (Bellinger et al., 1987; Dietrich et al., 1987). Marsh et al. (1987) examined 81 infant-mother pairs and demonstrated a dose-response relationship between hair mercury concentrations during gestation and the frequency of psychomotor retardation, seizures, and neurological signs in the children. Lewis, Worobey, Ramsay, and McCormak (1992) determined lead, cadmium, mercury, cobalt, chromium, nickel, and silver in amniotic fluid taken from 92 pregnant women undergoing amniocentesis. A prenatal toxic risk score based on the levels of the seven metals was derived which was negatively related to the intellectual development and health status of the subjects' children at 34 months of age. While lead as an environmental teratogen has been recognized for many years, the above summarized studies suggest that in utero exposure to lower levels of lead and other metals than are still considered safe by some governments are linked to congenital abnormalities and retardation.

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