- Email: [email protected]
Aerometric and hair trace metal content in learning-disabled children
~UVIKONMEN~AL
RESEARCH
Aerometric
DANIEL
25, 325-339 (1981)
and Hair Trace Metal Content Learning-Disabled Children
L. ELY, RICHARD
A. MOSTARDI, NANCY DAWN WORSTELL
in
WOEBKENBERG,
AND
Received September 11. 1980 Children in the fourth to sixth grades at two schools were studied and divided in a control group (II = 323) and a learning disability (LD) group (n = 77). The following trace metals were analyzed in the air (7 months) at the two schools and in the children’s hair: cadmium, selenium. arsenic, mercury. and lead. Discriminant analysis showed that selenium, mercury. cadmium. diastolic blood pressure. arsenic. and sex (all P < 0.001) were able to correctly classify 79.9% of the cases into LD or control groups. LD females had elevated selenium (P i .05) and lower diastolic blood pressure (P < 0.05) as compared to controls. LD males had elevated selenium (P c 0.001) and cadmium (P < 0.01). and lower systolic and diartolic blood pressure (P < 0.001) and mercury (P < 0.05) as compared to controls. The aerometric data showed that although there was a positive correlation between air and hair, lead, mercury, and selenium the absolute values were well below Federal Standards (PB = 276 rig/m”, Hg = 1.5 npim”, Se = 1.75 ng/mJ). The data suggest that there is a significant difference between LD and control trace metal hair content and blood pressure, but that the air is not a major source of this effect although it does add to the cumulative trace metal hair content.
INTRODUCTION
There is a growing concern about the physiological and behavioral effects of environmental trace metals in human populations. Previous reviews have reported on the sources and physiological and toxicological effects of these elements (Friberg. 1950; Fleming and Walsh, 1957; Underwood, 1977; Pfeiffer, 1975; Muth et trl., 1967; Kovaliskii and Ermakov, 1970; Zingaro and Cooper, 1974; Fleischer rr al., 1974), but few studies have examined the behavioral effects of environmental exposure to trace metals. Lead has received the most attention and several studies have examined the physiological and behavioral effects of lead with reference to hyperactivity in children (Needleman et al., 1979: Wessell and Dominski, 1977; David et nl., 1976; Kopito et al., 1969; Kotok, 1972: White and Fowler, 1960). The neurological effects of high dosages of lead have been established, but subtle effects of low dosages are not as numerous (Chattopadhyay er ul., 1977). It has been shown that in hyperactive children lead levels were elevated and inversely related to performance (David er al., 1976). Selenium studies in monkeys have demonstrated behavioral effects with typical signs of brain lesion and lathyrism (Rudra, 1952), and Rosenberg et al. (1966) found that selenium changed the conduction properties of the neural signal. Also chronic cadmium treatment in rats has produced CNS effects, such as decreased medullary serotonin levels, whereas. striatal dopamine and cerebrocortical acetylcholine were significantly 325 0013-9351/81/040325-15$02.00/O Copyright 411 right\
7 1981 by Academic Pra\. Inc. of repmducuon in any form rewrvrd
326
ELY
ET AL.
elevated (Singhal et al., 1976). Cadmium was found to inhibit two catecholamine degradative enzymes in vitro (Revis, 1978). However, the effects of low levels of trace metals on the central nervous system and concomitant behavioral effects specifically in children have not been well studied although the evidence warrants further study (Roels et al., 1980). It is a relatively recent development to examine hair trace element% in specialized groups. One of the first studies in this area showed that zinc supplement administered to zinc-deficient dwarfs increased hair levels of zinc (Prasad, 1966). Reviews of trace elements in hair can be found in Creason et al. (1975), Brown (1974), Eads and Lambdin (1973), and Gordus (1973). Pihl and Parkes (1977) examined the hair content of 14 elements in a group of learning-disabled (LD) children. They reported the following elements were significantly elevated in the LD children: sodium, cadmium, lead, manganese, and chromium. However, in a later report by this group the same measurements were made and the previous significant differences were not found (Pihl et al., 1979). They offer several possible explanations involving potential nutritional and medication changes and the entry into adolescence of many subjects. The objective of the present study is to further examine the relationship between hair trace metals and learning disabilities in children. This project is a substudy of a larger study designed to examine the effects of air pollution on the health of children in Akron, Ohio. We report only on the trace elements in the hair of children and in the air in the immediate vicinity. MATERIALS
AND METHODS
Children in the fourth-sixth grades (ages 9- 12) from two schools (School S and School B) in Akron, Ohio, were requested to participate in the trace metal study which involved analyses of hair trace metals. Of a total of 466 children there were 323 that agreed to participate and comprised the control group. Also there were 77 children in the learning disability (LD) group from the same two schools who participated from a total population of about 100 LD children. The LD children had been evaluated by a multidisciplinary team consisting of a district psychologist and the child’s teacher according to the State of Ohio procedures for evaluating specific learning disabilities (Title 45-Public Welfare, Sections 121a.532 le and 121a.601). Briefly, the LD children functioned within the normal range of intelligence or above (attained IQ above 80), but were below expectancy in one or more of the following areas: oral expression, listening comprehension, written expression, basic reading skills, reading comprehension, mathematic calculation, or mathematic reasoning (achievement 2 standard errors of measurement below the expected level of achievement for his specific ability level). The State definitions of learning disability exclude the mentally retarded, neurological pathology cases, and the emotionally disturbed. Some of the LD children were in special classes, whereas other LD children were in regular classes but had a tutor. The analyses of these subdivisions are presented under Results. Hair samples were collected from each child between October 1976 and April 1977 according to the procedures of the Trace Element Laboratory, Case Western Reserve University, and then sent to that laboratory for analysis of cadmium, arsenic, lead, selenium, and mercury by means of atomic absorption spectroscopy
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
327
(Strain ct al., 1972). The 77 LD children in this study were already in existing learning disability programs. Socioeconomic information was collected on the children’s parents using the Blishen (1967) socioeconomic index and race and medication history were recorded for the children. Aerometric data were collected at the two schools studied. Total suspended particulate (TSP) levels were measured using the high-volume sampling procedure as described in the Federal Register (36:8186, 1971). The stations were operated daily for a 24-hr period beginning and ending at 8:00 AM from October 1977 to June 1978. Each unit had a Sierra Flow controller to maintain flow at 1.13 m3/min. The filter papers were supplied and weighed by a Community Health Assessment Monitoring Program (CHAMP) subcontractor, Stewart Laboratories, Knoxville, Tenn. The trace elements were determined as weekly composites of the filters. The station at School S was located adjacent to the school and along a moderately traveled city street. The station at School B was on top of a IO-ft roof on the school. This school is also bordered on the east by a city street with moderate traffic and is about 4 km from the other school. These two schools and the associated air-monitoring stations are located in a “walking” school district. Ninety-five percent of the students walk to and live within 1 mile of the school. School S is located closer to the known point sources of air pollution in the area. Blood pressure was determined by a licensed medical technician using standard sphygmomanometry (Baumanometer) techniques and a pediatric cuff. The children were at rest in a sitting position and the average of three readings was taken for analysis. The statistical procedures used in this study include analysis of variance, correlation coefficients, Student’s t tests, discriminant function analysis (Wilks), and multiple regression. RESULTS
Table 1 shows the trace metal results of the two groups. Using Student’s t tests it was found that the LD females showed a significant elevation in selenium (P < 0.05) as compared to the control females. Blood pressure analysis showed that the LD females had a lower diastolic blood pressure than control females (P < 0.05). There were no significant group differences between cadmium, lead, mercury. arsenic, or systolic blood pressure. Analysis of the male data shows the same basic trend with cadmium (P < 0.01) and selenium (P < 0.001) significantly elevated in the LD groups as compared to the controls, but in the LD males both systolic and diastolic blood pressure and mercury showed lower values than the controls (P < 0.001). A multiple regression analysis was performed to determine the amount of variance contributed by the metals to blood pressure. In the control males using systolic blood pressure as the dependent variable the five metals only explained 2% of the variance and in the females they explained 8%. For diastolic pressure the metals explained 4% in the control males and 1% in the females. However, in the LD group the metals explained 40% of the systolic pressure variance and 54% of the diastolic variance in the females. In the LD males the metals explained 1 ICC
328
ELY ET AL. TABLE TRACE METALS
FROM
1
HAIR SAMPLES AND BLOOD PRESSURE IN LEARNING CONTROL CHILDREN FROM Two SCHOOLS
DISABILITY
Trace metal (ppm) Group Control Females LD Females Control Males LD Males
Age (years)
N
Pb
9- 12
139
9-12
20
9- 12
184
9-12
57
15.39 + 1.3 11.9 k 1.9 14.27 20.88 16.2 2 1.4
Cd 1.07 kO.10 1.20 co.07 0.97 kO.03 1.13** kO.05
Hg 18.11 21.1 15.9 k0.96 17.0 20.71 14.3* to.62
AND
Blood pressure Se
0.86 kO.10 1.4.5* kO.11 0.73 to.03 1.40*** kO.08
As
(mm Hg)
1.24 to. 12 1.20 *o. 13 1.05 20.06 1.04 50.07
m 2 1.2 64 k 0.8 92* 24.0 58* + 2.7 992 1.0 63 k 0.7 s*** t 1.5 57*** + 1.3
Note. Values are + SE. LD group compared to respective control by sex, Student’s I test: “P < 0 .05., **P < 0.01; ***p < 0.001.
of systolic and 15% of diastolic variance. It was apparent that cadmium and selenium explained most of the variance in the LD group, whereas the metals explained very little of the blood pressure variance in the controls. An analysis of variance of the live elements showed three significant differences between the two groups for each sex (P < 0.01) for cadmium, selenium, and mercury. With regard to blood pressure and metals there was a significant group difference in both males (P < 0.05) and females (P < 0.01) in a two-way interaction between diastolic blood pressure and selenium. In both males and females there was a significant main effect on systolic blood pressure (P < 0.02) between the two groups. In order to examine the data for each school and to correlate aerometric data with hair data in each school we divided the LD and control groups by schools (Table 2). Analysis of this grouping using Student’s t tests showed that LD children in School S had higher levels of cadmium (P < 0.01) and selenium (P < O.OOl), and lower blood pressure (P < 0.01-0.001) than control children in the same school. LD males in School B had higher lead (P < 0.05) and selenium (P < 0.001) levels than control males in the same school. However, these trends were not observed in the LD females of School B. Also in the controls it was found that males in School S had significantly elevated hair lead (P < O.OOl), mercury (P < O.OOl), selenium (P < O.Ol), and systolic and diastolic blood pressure (P < 0.01) as compared to School B controls. The LD children in School S had higher cadmium levels (P < 0.05) and lower blood pressure (P < 0.05) than’LD children in School B. It is interesting that the aerometric data (Table 6) also shows higher air lead, selenium, mercury, and arsenic in School S as compared with School B. Discriminant analysis on all LD children as compared to controls showed that the best discriminators (P < 0.001) were selenium, mercury, cadmium, diastolic blood pressure, arsenic, and sex (Table 3). These variables correctly classified 79.% of the grouped cases. The disctiminant analysis by sex showed that in males the best discriminators (P < 0.001) were selenium, diastolic blood pressure, mercury, and lead which correctly classified 82.9% of the cases. Among the
Note.
9-12
School
LD compared
Y- 12
School LearningS Disability
Values
9- 12
School S Controls
Learning Diability
are *SE.
9912
B
Wears)
Group
School B Controls
Age
CHIL~K~~
TKAC~
19
M
18.5 23.2
17.2 24.4
17.2 21.6
15.1 _f 1.4 13.4 t 1.4
k 1.7
11.5 1-0.83 9.6
***P
14.5
1.33”‘” kO.08
< 0.001.
ro.15
1,4p ..:.
20.09 0.75 so.05 0.82 20.06 ].53^“. to. I7
20.8 18.7 t I.2 19.7 i 1.5 15.0 21.9
? 1.0
l,36v+
14.2
.99 20.04 1.11 k-o.09 1.03 20.06 0.83 20.06 0.94 20.05 I .40’: 20.05 :‘.
Se
0.66 20.03 1.41 20. I4
(ppm)
14.9 20.3 16.3 21.1
Hi?
metal
0.98 to.2
Trace
SCH~OI.
DISABII.IT>
IN EACH
IN LEARNING
COUNTERPARTS
PRESSURE
17.3 + 1.8
1.33 kO.2
Cd
CONI-ROE
-+*P <: 0.01:
THEIR
2
BLOOD
TABLE ES END
17.3 i-2.2
Pb
AND
SAMPI
by sex: *P < 0.05:
6
81
M F
73
F
38
14
F
M
103
M
N
SCHOOL
66
EACH
HAIR
F
Sex
FRO~I
4~ $ FROM
to control
MFI
1.10 -to.10
1.01 20.09 1.03 to.06 1.04 20.06 1.27 20.12
1.04 kO.1 1.16 to.17
1.44 kO.2
As
i a
54. “... &T
.:.:: 2 2
E n 1 F jy
r" 85^” 5 a.:. :/: -+ +-_ 7
z 6 G; >
!i
F
2
iz
g m K 2
662-i
103 + 2
9522 59 2 2 2 106 3 68i-T
9821 62 -c 0.9 k 95 5 -E-t3
9711 ? 95 1
Blood pressure (mm I-k)
330 DISCRIMINANT
FUNCTION ANALYSIS THE MOST SIGNIFICANT
ELY ET
AL.
TABLE
3
(WILKS) VARIABLES
BETWEEN LD AND DISCRIMINATING
CONTROL THE Two
CHILDREN GROUPS
SHOWING
Percentage grouped cases correctly classified
Variable
Wilks h
Significance (P)
Both sexes
Se & Cd BPD As Sex
0.909 0.825 0.769 0.731 0.716 0.703
79.9
Males
Se BPD Hg Pb
0.646 0.623 0.609 0.603
82.9
Females
BPD Se Cd BPS Pb HE?
0.950 0.932 0.831 0.800 0.778 0.760
=0.02 =0.02
80.5
females the best discriminators (P < 0.05) were diastolic blood pressure, selenium, cadmium, systolic blood pressure, lead, and mercury which correctly classified 80.5% of the cases. Within the LD group lead, cadmium, blood pressure, and mercury discriminated correctly between the two schools in 70% of the male cases and 80% of the female cases. Table 4 shows the results of further subdivision of the LD children into those tutored on an individual basis but in a regular class and those in a special all-LD class. There was only one significant group difference in trace metals. Selenium was higher in the special LD class but this was attributed to chance. There were no blood pressure and no significant sex differences within or between groups. When each school was compared to the other using these same LD subdivisions the tutored LD children from School S showed higher levels of lead (P < 0.01) and cadmium (P < O.OS), but lower systolic (86 mmHg vs 95 mmHg, P < 0.05) and diastolic blood pressure (50 mmHg vs 61 mmHg, P < 0.01) than the tutored LD children from School B (n = 13 and n = 28, respectively). This was the same trend as before showing that children from School S have higher trace metal hair content. About 27 of the 77 LD children lived outside the school district; however, there were no significant trace metal or blood pressure differences when they were compared to the resident LD children (Student’s t test). The results of the correlations between hair elements and blood pressure and metal-metal interactions for the five metals are shown in Table 5. There were 20 possible interactions with this combination of variables and 12 of them showed significant correlations in the control group and 6 in the LD group. Cadmium and selenium were inversely related to blood pressure, however, directly related to
TRACE
METALS
IN
LEARNING-DISABLED TABLE
HEAVY METALS DIFFERENT
FROM GROUPS
331
CHILDREN
4 AND BLOOD
HAIR SAMPI.ES OF LEARNING
PRESSURE
DISABILITY Trace
II\;
CHILDREV
metal (ppm) Blood pressure (mm Hg)
Age (years)
Sex
N
Pb
Learning DisabilityTutored School B
9-12
Both
28
12.5 _f 1.8
1.01 kO.07
14.3 50.9
1.2 50.09
1.10 t-O.13
yJz2 61 27
Learning DisabilityTutored School S Learning DisabilityTutored Both Schools
9m 12
Both
13
21.2** k2.9
1.28 to. IO
15.2 k 1.3
1.3 20.15
1.20 -0.13
86- 2 3 5t.F” tZ
9- 12
M
32
16.5 k 1.8
1.06 +0.07
14.6 -to.9
I.? TO.09
1.04 ~0.10
92 z 2 3i-=iT
F
9
M
25
10.8 -c3.2 15.8 22.2
1.20 to.12 1.22 20.07
14.6 2 1.3 14.0 20.9
1.4 kO.16 1.6*’ 20.13
1.40 20.23 1.04 to.09
S=& 28 t 5 yj4-2 57 2 2
F
11
12.7 ~2.3
1.19 io.09
17.0 ~1.3
1.5 kO.16
1.03 +-&I3
9126 58 27
Group
Learning DisabilitySpecial Class Both Schools
9p 12
Cd
Hg
Se
AS
Nofr. Values are zSE. *P r: 0.05. **Pi 0.01.
each other (r = 0.80, P < 0.001 in controls and r = 0.23. P < 0.05 in LDs). It is interesting to note that all the metals were directly related to each other in the controls but only cadmium was strongly correlated with the other metals and blood pressure in the LD group. Table 6 shows the aerometric trace metal results measured from October 1977 TABLE CORRELATION
HAIR
COEFFICIEWTS
ME~AL~METAL
Control SBPP Cd SBP-Se DBP&Cd CdGPb Cd-Hg Cd-Se Cd-As Pb-Hg PbbSe Pb-As Se-Hg Se-As As-Hg Nofr. selenium.
-0.15 -0.13 -0.06 0.50 0.47 0.80 0.54 0.28 0.43 0.32 0.52 0.56 0.35
BETWEEN
INTERACTIONS
5 ME.FALS .*ND BLOOD PRESSURE 4%~ FOR THE Two GROVPS FOR FI\.E METALS HAIR
Level of significance (P)
LD
Level of significance (P)
=0.02 =0.03 N.S.
-0.19 -0.06 -0.25 0. I? -0.31 0.23 0.35 -0.10 -0.01 -0. I’ -0.08 0.03 -0.26
=0.05 N.S. =O.O? N.S. x0.0 I =0.02 =O.OOl N.S. N.S. N.S. N.S. N.S. =O.Ol
SBP = systolic blood pressure, DBP = diastolic Pb = lead. Hg = mercury. As = arsenic,
blood
pressure.
Cd = cadmium.
Se x
332
ELY
ET AL.
TABLE AEROMETRIC
TRACE
METALS
Oct. 1977 B S Nov. 1977 B S Dec. 1977 B S Jan. 1978 B S Apr. 1978 B S May 1978 B S June 1978 B S
Note.
B
School
S
Values
are average
6
FOR 7 MONTHS
Trace
Sampling period and school
Average School
MEASURED
metal
AT EACH
OF THE
SCHOOLS
in air (rig/m?
As
Cd
6.4 10.5
2.5 2.4
1.9 1.0
363 441
1.4 1.5
6.0 10.8
2.3 1.9
1.5 1.1
209 240
1.2 1.8
15.9 12.8
5.2 3.3
1.0 1.3
412 429
2.6 1.6
1.9 5.8
0.1 0.5
0.3 1.8
123 217
0.6 1.0
1.1 9.7
0.5 3.1
0.3 4.4
46 265
0.3 1.1
6.6 6.5
1.3 0.7
1.3 2.1
227 235
2.2 3.2
8.9 8.5
1.6 1.6
1.6 1.3
341 319
2.8 3.6
6.7 24.9 9.2 52.5
1.9 2 1.7 1.9 kl.l
1.1 to.6 1.9 k1.2
246 1134 307 2 94
1.6 kO.9 1.9 + 1.0
Jk
Pb
Se
&SD.
through June 1978. Measures during February and March are missing due to heavy snows and equipment shutdown. There were no significant trace metal differences using Student’s t test between the two schools. However, discriminant function analysis showed that cadmium (P = O.Ol), mercury (P = 0.009), and arsenic (P = 0.13) were significant discriminators between the two schools and correctly predicted 93.8% of the cases. School S had higher values of arsenic and mercury as compared to School B. The trace metals were measured from the total suspended particulate fraction of air (TSP) and analysis of same day TSP samples between the two schools showed no significant difference (School S TSP = 48.7 r&m3 and School B TSP = 45.9 ng/m3), which indicates that the trace metal differences in the two schools were not due just to differences in TSP levels. DISCUSSION
There was a consistency of trace metal values found throughout the data that showed cadmium and selenium elevated in the LD children. This was substan-
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
333
tiated in two different schools located approximately 4 km apart in the Akron, Ohio, area. Also the diastolic blood pressure was consistently lower in the LD children. The lowered diastolic blood pressure in the LD children is difficult to explain. Previous studies have examined the role of cadmium and blood pressure with conflicting results. Recently, Whanger (1979) did not find any relationship between blood or hair cadmium and blood pressure in Oregon residents from different occupations. Cadmium has induced hypertension in mice and rats (Schroeder, 1965: Perry, 1976); however, others have not observed hypertension with cadmium loads in animals (Friberg ef cll., 1971; Porter et LzI., 1974). Since the LD children had higher levels of hair cadmium than controls, and yet lower diastolic blood pressure, the effect appears to be paradoxical. It is possible that behavioral or dietary differences at school and home could have influenced the blood pressure of the LD children. However, analysis of the LD children taking medication (n = 13) which was mostly Ritalin showed that there was no difference in systolic and diastolic blood pressure as compared to LD nonmedicated children (Student’s f test). There also were no significant differences with regard to medication and the trace metals. Racial differences cannot explain the observed differences either, since only 3 LD children were black and there were no significant differences with regard to trace metals or blood pressure between white and black LD children. However, multiple regression analysis showed that in the LD group the metals explained ll- 15% of the male and 40-54s of the female blood pressure variation. This was a severalfold increase in explaining the variance as compared to the controls. This suggests that in the LD females, especially, the metals could be interacting in such a way as to lower peripheral resistance and thereby lower blood pressure. However, the possibility of a centrally mediated mechanism cannot be ruled out due to studies showing cadmium effects on neurotransmitters (Singhal et NI., 1976) and catecholamines (Revis, 1978). A longitudinal follow-up of these children is planned to examine the influence of medication, diet, and behavioral therapies upon trace metals, blood pressure, and learning disability. There was no significant difference between LD and control groups with regard to socioeconomic level (42.2 vs 41.9, respectively). With regard to the elevated cadmium in the LD children a question arises as to the source. Previous studies show that cadmium contaminates the environment through smelting and refining of zinc and lead ores, recovery of scrap metal, combustion of coal and oil, disposal of sewage sludge and waste plastics, battery wastes, electroplating, and phosphate fertilizer contamination (Underwood, 1977: Friberg et nl., 1971; Fleischer ct nl., 1974; Fulkerson and Goeller, 1973). It has been estimated that 58% of the cadmium-consuming industry in the U.S. is located in the Great Lakes states (Fasset, 1972). However, tnere is no reason to believe the LD children were differentially exposed to the trace metals. For smokers the main source of cadmium is through inhalation of cigarette smoke (Underwood, 1977; Shuman et crl.. 1974; Lewis et al., 1972) but for nonsmokers the main source is food followed by air then water, with an average intake of about 20-50 rig/day (Fleischer ef (11.. 1974). However, less than 5% of ingested cadmium is absorbed, the remainder excreted with the feces (Friberget crl., 1971). Hair cadmium content
334
ELY
ET AL.
does appear to reflect exposure to the element. Whanger (1979) found that blood and hair cadmium in Oregon residents was highest in employees of a mine versus offtce workers, smokers versus nonsmokers, and metal workers versus office workers. Body cadmium levels have previously been detected through blood and urine levels, but animal and human studies suggest these are not reliable measures of total cadmium body burden (Carlson and Friberg, 1967; Petering et al., 1973), whereas other studies indicate blood cadmium is a sensitive measure of recent (3 month) exposure (Kjellstrom, 1979). One group found that with heavy cadmium exposure (cadmium salt factory) the blood level of cadmium plateaus after 120 days, whereas urine levels have several complex phases dependent upon dosage and time (Lauweryset al., 1979). Several investigators have successfully used hair as an indicator of the body burden of cadmium (Nordberg and Nishiyama, 1972; Brancato et al., 1976) and others have reported on hair measurements for several trace metals (Hambridge and Droegemueller, 1974; Hammer et al., 1971; Klevay and Hyg, 1973; Maugh, 1978; Petering et al., 1971; Grandjean, 1978). The children in this study were not smokers although we do not have data on the smoking habits of the LD parents. It is possible that parental smoking could affect the children’s hair cadmium level. However, surface contact of hair with smoke should not seriously affect the hair analysis of cadmium since the hair was digested in double-distilled nitric acid and washed thoroughly ten times in doubledistilled water before analysis. To support this contention we did not observe any hair trace metal differences in the control children between those living in “smoking” households and those living in “nonsmoking” households. With regard to selenium sources and effects, the major source is the diet (Underwood, 1977) and selenium disulfide has been found in shampoos and skin medications (Cooper et al., 1974). Water is only a minor source of selenium ranging from 0.1-100 q/liter (Davis and Dewiest, 1966). However, industrial sources of selenium include: glass, pigment, and steel production; rubber curing; and electrolytic copper refining. Physiologically, selenium is deposited in hair, kidney, and liver, and minimally in brain, muscle and fat (Dickson and Tomlinson, 1967; Masson and Young, 1967). The compounds of selenium influence metabolic activities such as oxidative phosphorylation (Wilson and Bandurski, 1956). It also has powerful antioxidant properties (Tappel and Caldwell, 1967) and can bind to: hemoglobin (McConnell and Cooper, 1950), leukocytes (McConnell, 1959), fibrinogen (Celander et al., 1962), and myosin and aldolase in muscle (McConnell and Roth, 1964). Since our data show cadmium and selenium both elevated in the LD children it is interesting to note that recently interactions have been reported between selenium and cadmium. Whanger (1979) showed that selenium decreased the accumulation of cadmium in rat liver and kidney. Also selenium has been reported to limit the binding of cadmium in tissues of the testes, kidneys, and plasma (Chen et al., 1975). The mechanism of action of selenium may be similar to that of cadmium since they both have a propensity for reacting with sulfhydryl groups of proteins (Barron, 1947). It appears that with minimal amounts of selenium present cadmium
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
335
toxicity is reduced. Therefore, the high-selenium hair content in the LD group may be a physiological adaptation to altered cadmium metabolism. The subject of long-term health effects specifically of these two metals have been reviewed in a number of reports and symposia (Friberg e1 crl., 1971; Fleischer et ul., 1974: Fulkerson and Goeller, 1973; Muth er nl., 1967: Kovaliskii and Ermakov, 1970: and Zingaro and Cooper, 1974). It is interesting to compare our results with those of Pihl’s laboratory (original investigator in this area) since we both used the same trace element laboratory to analyze our hair samples (Trace Element Laboratory, Case Western University). Although very little data exist on learning disability and trace metals, Pihl (1975) has thoroughly reviewed the area and his laboratory showed in 1977 that there were strong correlations between LD children and specific trace metals. In their original study cadmium, cobalt, manganese, chromium, and lithium separated the control and LD groups in a discriminant analysis with 97.5% accuracy (Pihl and Parkes, 1977). However, in a follow-up study about 2 years later there was no significant discrimination between the two groups mainly because the LD group values returned toward control baseline (Pihl et ml., 1979). They suggested that these element changes could be due to treatment of the LD group with medication, dietary changes, behavioral therapies, and aging effects. Our value of elevated cadmium in the LD group (1.16 ppm) is lower but in general agreement with the elevated cadmium levels in their original LD groups (1.72 ppm), and our control values are similar (0.94 vs 1.08 ppm, respectively). Our elevated selenium values and blood pressure results cannot be compared because they were not measured in Pihl’s studies. One objective of our study was to determine the trace metal content of the air the children were breathing in order to determine if this was an important source. Our data suggest that the air trace metals in the study area were not elevated as compared to other cities, but there were correlations between trace metal content of the air and hair. However, it should be noted that the aerometric data were collected about one year after the hair samples. We do not believe that this invalidates the results because in our continuous monitoring of the air at these two locations there has been minimal variation over a 2-year period when the same months are compared. Schroeder (1970) has reviewed the data on the concentration of cadmium in the air of the United States and gives a range of cadmium in urban areas of 2-370 r&m” and 0.4-26 ng/m3 for nonurban areas. Other areas in Ohio have been reported by Lee et nl. (1968) as follows: Cincinnati downtown, 80 rig/m” : and Fairfax (suburban), 20 rig/m”. Athanassiasdis ( 1969) reported a maximum of 130 ngim3 in 1960 for Akron, Ohio. However, recently the air in Akron has become cleaner with better air pollution controls and reduced industry. Our values show a range of 0. l- 5.2 ng/m3 of cadmium in Akron which is very low compared to the NIOSH recommendation of 40 ng/m3 (Fairchild et trl., 1977). Also the aerometric levels of lead and selenium were relatively low in our study areas. It does not appear that the air is a main source of trace metal exposure for the children in our study area. However, in School S with the highest air lead, mercury, and selenium the children (LD and control) reflected higher hair levels of these same elements than children in School B which indicates an association
ELY ET AL.
336
between aerometric and hair trace metal levels. The interactive effects of low levels of trace metals upon CNS function and the explanation for the LD differences remain to be determined. The subtle neurologic effects of chronic low-grade lead poisoning concern many because of the strong possibility of its connection to the 10% or more children suffering from learning disabilities. Needleman et al. (1979) in a tightly controlled study found deficits in psychologic and classroom performance of children (first and second grades) associated with elevated dentine lead levels. The deficits were apparent in general intelligence scales, verbal subtests, and auditory- or speech-processing tests. This study suggests that chronic exposure to low lead levels (below 30 pg/dl blood standard) may lead to central nervous system alterations. Numerous studies suggest that moderate elevations of blood lead (40-70 pg/lOO cc) are an important factor in producing significant impairment in cognitive, verbal, perceptual, and fine motor skills when compared to a control group with levels below 30 pg/lOO cc (Perrino and Erphart, 1974; Landrigan et al., 1975; de la Burde and Choate, 1975). Although our studies did not show consistently elevated lead levels in the LD children the results did show that in the school with highest air lead concentration the LD children showed higher lead levels than the controls in the same school. If these LD children were exposed to the same air, water, and dietary levels of trace metals, then there appears to be a metabolic difference in the handling of the trace metals. It is not possible from our data to suggest a cause-effect relationship between learning disability and trace elements, but the data from two different laboratories now indicate that the effects of trace elements on learning disability and behavioral effects should be further examined in longitudinal studies. ACKNOWLEDGMENTS The authors would like to express appreciation to the following people for their contribution to this study: the principals of the two schools involved, Mrs. Scholl and Mrs. Dann; the students involved in the study; and Mary Begley for typing the manuscript. This research was supported under EPA Grant 80425601, 02.
REFERENCES Athanassiadis, Y. C. (1969). Air Pollution Aspects of Cadmium and Its Compounds. U.S. Clearinghouse Fed. Sci. Techn. Inform. PBl88, 086, pp. l-77. Barron, E. S. (1947). Inhibition of succinic oxidase by heavy metals and its reactivation with dithiols. Biochem.
J. 41, 346.
Blishen, B. (1967). A socio-economic index for occupations in Canada. Canad. Rerr. Sot. Anthrop. 4, 41-53. Brancato, D. J., Picchioni, A. L., and Chin, L. (1976). Cadmium levels of hair and other tissues during continuous cadmium intake. J. Toxicol. Environ. Health 2, 351-359. Brown, A. C. (1974). “The First Human Hair Symposium.” Medcom Press, New York. Carlson, L. A., and Friberg, L. (1967). The distribution of cadmium in blood after repeated exposure. Stand. J. Clin. Lab. Invest. 9, l-4. Celander, D. R., Jaguo, M., and Naschke, M. D. (1962). Biosynthetic labelling of fibrinogen and other proteins with radioselenium. Fed. Proc. 21, 36. Chattopadhyay, A., Roberts. T. M., and Jervis, R. E. (1977). Scalp hair as a monitor of community exposure to lead. Arch. Environ. Health 32, 226-236. Chen, R. W., Whanger, P. D., and Weswig, P. H. (1975). Selenium-induced redistribution of cadmium binding to tissue proteins: A possible mechanism of protection against cadmium toxicity. Bioinorg. Chem. 4, 125.
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
337
Cooper, W. C., Bennett, K. G., and Croxton, F. C. (1974). The history. occurrence. and properties of selenium. In “Selenium” (R. A. Zingaro and W. C. Cooper. Eds.). Van Nostrand-Reinhold. Princeton, N.J. Creason J. P., Hinners. T. A.. Bumgartner, J. E., and Pinkerton. C. ( 1975). Trace elements in hair as related to exposure in metropolitan New York. Clin. Cl~rm. N. l’. 21. 603-612. David, 0.. Hoffman, S. P.. Sverd, J.. Clark, J., and Voeller K. (1976). Lead and hyperactivity. Behavioral response to chelation: A pilot study. Amer. ./. Psyc-lriut. 133, 1155- 1158. Davis. S. N.. and Dewiest, R. J. M. (1966). “Hydrogeology.” Wiley. New York. de la Burde, B.. and Choate, M. S. (1975). Early asymptomatic lead exposure and development at school age. J. P~dicrr. 87, 638-641. Dickson, R. C.. and Tomlinson. R. H. (1967). Selenium in blood and human tissues. Cliff. C/ii/jr. Ac./o 16. 311. Eads, E. A., and Lambdin. C. E. (1973). A survey of trace metals in human hair. t‘n\~ir~~n. Kcs. 6. 247-252. Fairchild, E. J.. Lewis. R. L., and Tatken, R. L. (Eds.) (1977). “Registry ofToxic Effects ofchemical Substances,” Vols. 1 and II, U.S. Dept. HEW, Cincinnati. Fassett, D. W. (1972). Cadmium. In “Metallic Contaminants and Human Health” (D. H. K. Lee. Ed.), pp. 97- 124. Academic Press, New York. Fleischer. M., Sarofin. A. F., Fasset. D. W., Hammond, P., Shacklette. H. T.. Nisbet. I. C. T.. and Epstein, S. (1974). Environmental impact of cadmium: A review by the panel on hazardous trace substances. Ent~iron. Heulth Pc~rsp~ci. 7, 253-323. Fleming. G. A.. and Walsh, T. (1957). Selenium occurrence in certain Irish soils and its toxic effect in animals. Proc.. Roy. Irish Acud. Sect. B 58, 151. Friberg, L. (1950). Health hazards in the manufacture of alkaline accumulators. with special reference to chronic cadmium poisoning. Actor Med. Scrrncl. 138, Suppl. 240. Friberg. L.. Piscator. M.. and Nordberg. G. (1971). ‘*Cadmium in the Environment.” Chem. Rubber Pub. Co.. Cleveland. Fulkerson, K., and Goeller. H. E.. Eds. (1973). “Cadmium: The Dissipated Element.” Oak Ridge National Laboratory Pub. No. ORNL NSF EP 21, Oak Ridge, Tenn. Gordus. A. (1973). Factors affecting the trace-metal content of human hair. J. Rrldiorrrrul. Chum. 15. 229.-243. Grandjean, P. (1978). Lead concentration in single hairs as a monitor of occupational lead exposure. fnr. Arc~lz. Ckwp. Envitm. H~rrlth 42, 69-82. Hambridge. K. M.. and Droegemueller. W. (1974). Changes in plasma and hair concentrations of zinc. copper. chromium. and manganese during pregnancy. Ohstc,r. C;~nc,c~o/. 44. 666-672. Hammer. D. I.. Finklea. J.. Hendricks, R., Shy, C., and Horton, R. (1971). Hair trace metal level\ and environmental exposure. Amer. J. Epidemicd. 93, 84-92. Kjellstrom, T. (1979). Exposure and accumulation of cadmium in populations from Japan. the United States. and Sweden. Enl~iron. Health Perspect. 28, 169- 197. Klevay. L. M.. and Hyg, S. V. ( 1973). Hair as a biopsy material. Avt,ll. E/r\,irott. Hrtrlrh 26, 169- 172. Kopito. L.. Briley. A. M.. and Schwachman. H. (1969). Chronic plumbism in children. Amc,,-. .Zlr,c/. A .YSO~~. 209. 243 - 248. Kotok. D. (1972). Development of children with elevated blood lead levels: a controlled study. .1. I’(,t/. 80. 57-61. Kovaliskii. V. V.. and Ermakov, V. V. (1970). “The Biological Importance of Selenium.” National Lending Library for Science and Technology (Publisher), Yorkshire. Landrigan. P. J.. Baloh, R. W.. Barthol, W. F., Whitworth, R. H., Staehling. N. W., and Rosenbloom. B. F. (1975). Neurophyschological dysfunction in children with chronic low-lead level lead absorption. Lancef 1, 708-712. Lauwerys. R.. Roels. H.. Regniers, M., Buthet. J. P., Bernard, A., and Goret, A. (1979). Significance of cadmium concentration in blood and in urine in workers exposed to cadmium. Eursirorr. Rev. 20. 375-379. Lee. R. E.. Jr.. Patterson, R. K.. and Wagman, J. ( 1968). Particle-size distribution of metal compctnents in urban air. Environ. Sc,i. Te~hnol. 2, 288. Lewis. G. P., Jusko, W. J.. Coyghlin, L. L., and Hartz, S. (1972). Cadmium accumulation in man: Influence of smoking, occupation, alcoholic habit, and disease. .I. Chuo/~ic~. Div. 25. 717-726.
338
ELY ET AL.
Masson, K. E., and Young, J. 0. (1967). in “Selenium in Biomedicine” (0. H. Muth, Ed.), pp. 383-394, Avi Pub. Co., Westport, Conn. Maugh, T. H. (1978). Hair: A diagnostic tool to complement blood serum and urine. Science 202, 1271- 1273. McConnell, K. P. (1959). Selenium-75 binding in dog leukocytes. Texas Rep. Biol. Med. 17, 120. McConnell, K. P., and Cooper, 3. I. (1950). Distribution of selenium in serum proteins and red blood cells after subcutaneous injection of sodium selenate containing radioselenium. J. Biol. Chem. 183, 459. McConnell, K. P., and Roth, D. M. (1964). Selenium in rabbit skeletal muscle myosin. Fed. Proc. 20, 2990. Muth, 0. H., Oldfield, J. E., and Weswig, P, H., Eds. (1967). “Selenium in Biomedicine.” Avi Pub. Co., Westport, Conn. Needleman, H. L., Gunnoe, C., Leviton, A., Reed, R., Peresie, H., Maher, C., and Barrett, P. (1979). Deficits in psychologic and classroom performance of children with elevated dentine lead levels. N. Engl.
.I. Med.
300, 689-695.
Nordberg, G. F., and Nishiyama, K. (1972). Whole body and hair retention of cadmium in mice. Arch. Environ.
Health
24, 209-214.
Perrino, J., and Erphart, C. (1974). The relation of subclinical lead level to cognitive and sensorimotor impairment in black preschoolers. J. Learn. Disabil. 7, 26-30. Perry, H. M. (1976). Review of hypertension induced in animals by chronic ingestion of cadmium. In “Trace Elements in Health and Disease” (A. S. Prasad, Ed.), Vol. II, p. 417. Acad. Press, N.Y. Petering, H. G., Yeager, D. W., and Witherup, S. 0. (1971). Trace metal content of hair. Arch. Environ.
Health
23, 202-207.
Petering, H. Cl., Yeager, D. W., and Witherup, S. 0. (1973). Trace metal content of hair. II. Arch. Environ.
Health
27, 327-330.
Pfeiffer, C. C. (1975). “Mental and Elemental Nutrients.” Keats, New Canaan, Conn. Pihl, R. 0. (1975). Learning disabilities and intervention programs in the schools. In “Progress in Learning Disabilities” H. R. Myklebust, Ed.), Vol. III, pp. 10-28. Grune & Stratton, New York. Pihl, R. O., and Parkes, M. (1977). Hair element content in learning disabled children. Science 198, 204- 206. Pihl, R. O., Parkes, M., and Stevens, R. (1979). Nonspecific interventions with learning disabled individuals. In ‘*Rehabilitation, Treatment, and Management of Learning Disorders.” (R. M. Knights and D. J. Bakker, Eds.). Univ. Park Press, Baltimore. Porter, M. C., Miya, T. S., and Bousquet, W. F. (1974). Cadmium: Inability toinduce hypertension in the rat. Toxicol. Appl. Pharmacoi. 27, 692. Prasad, A. (1966). Metabolism of zinc and its deficiency in human subjects. In “Zinc Metabolism” (A. Prasad, Ed.). Thomas, Springfield, III. Revis, N. (1978). A possible mechanism for cadmium-induced hypertension in rats. Life Sci. 22, 479-488. Roels, H. A., Buchet, J. P., Lauwerys, R. R., Braux, P., Claeys-Thoreau, F., Lafontaine, A., and Verduyn, G. (1980). Exposure to lead by the oral and the pulmonary routes of children living in the vicinity of a primary lead smelter. Environ. Res. 22, 81-94. Rosenberg, P., Mantner, H. G., and Nachman, S. D. (1966). Similarity of effects of oxygen, sulfur, and selenium isologs on the acetylcholine receptor in excitable membranes ofjunctions and axons. Proc.
Nat.
Acad.
Sci. USA,
55, 835.
Rudra, M. N. (1952). Toxic principle of lathyrus sativus. Nature (London) 170, 125. Schroeder, H. A. (1965). Cadmium as a factor in hypertension. 1. Chronic Dis. 18, 647-656. Schroeder, H. A. (1970). A sensible look at air pollution. Arch. Environ. Health 21, 798. Shuman, M. S., Voors, A. W., and Gallagher, P. N. (1974). Contribution of cigarette smoking to cadmium accumulation in man. Bull. Environ. Contam. Toxicol. 12, 570-576. Singhal, R. L., Merali, Z., and Hrdina, P. D. (1976). Aspects of the biochemical toxicology ofcadmium. Fed. Proc. 35, 75-79. Strain, W. H., Pories, W. J., Flynn, A., and Hill, 0. A. (1972). Trace element nutriture and metabolism through head hair analysis. In “Trace Substances in Environmental Health” (D. Hemphill, Ed.). Univ. of Missouri Press, Columbia.
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
339
Tappel. A. L.. and Caldwell, K. A. (1967). In “Selenium in Biomedicine (0. H. Muth, Ed.). pp. 345-361. Avi Pub. Co.. Westport, Conn. Underwood. E. J. (1977). “Trace Elements in Human and Animal Nutrition.” 4th ed. Academic Press. New York. Wessel, M. A.. and Dominski, A. (1977). Our children’s daily lead. Amer. Ci. 65, 294-298. Whanger. P. D. (1979). Cadmium effects in rats on tissue iron. selenium, and blood pressure: blood and hair cadmium in some Oregon residents. Etlt~irotz. Herrlth Pcrspec~t. 28, 115% 121. White. H. H. and Fowler, F. D. (1960). Chronic lead encephalopathy. Pctliclr. 25. 309-315. Wilson. L. G., and Bandurski. R. S. (1956). An enzymatic reaction involving adenosine triphosphate and selenate. Arch. Biochem. Bioplzys. 62, 503. Zingaro. R. A.. and Cooper, W. C. (Eds.) (1974). “Selenium.” Van Nostrand-Reinhold. Princeton. N.J.
RESEARCH
Aerometric
DANIEL
25, 325-339 (1981)
and Hair Trace Metal Content Learning-Disabled Children
L. ELY, RICHARD
A. MOSTARDI, NANCY DAWN WORSTELL
in
WOEBKENBERG,
AND
Received September 11. 1980 Children in the fourth to sixth grades at two schools were studied and divided in a control group (II = 323) and a learning disability (LD) group (n = 77). The following trace metals were analyzed in the air (7 months) at the two schools and in the children’s hair: cadmium, selenium. arsenic, mercury. and lead. Discriminant analysis showed that selenium, mercury. cadmium. diastolic blood pressure. arsenic. and sex (all P < 0.001) were able to correctly classify 79.9% of the cases into LD or control groups. LD females had elevated selenium (P i .05) and lower diastolic blood pressure (P < 0.05) as compared to controls. LD males had elevated selenium (P c 0.001) and cadmium (P < 0.01). and lower systolic and diartolic blood pressure (P < 0.001) and mercury (P < 0.05) as compared to controls. The aerometric data showed that although there was a positive correlation between air and hair, lead, mercury, and selenium the absolute values were well below Federal Standards (PB = 276 rig/m”, Hg = 1.5 npim”, Se = 1.75 ng/mJ). The data suggest that there is a significant difference between LD and control trace metal hair content and blood pressure, but that the air is not a major source of this effect although it does add to the cumulative trace metal hair content.
INTRODUCTION
There is a growing concern about the physiological and behavioral effects of environmental trace metals in human populations. Previous reviews have reported on the sources and physiological and toxicological effects of these elements (Friberg. 1950; Fleming and Walsh, 1957; Underwood, 1977; Pfeiffer, 1975; Muth et trl., 1967; Kovaliskii and Ermakov, 1970; Zingaro and Cooper, 1974; Fleischer rr al., 1974), but few studies have examined the behavioral effects of environmental exposure to trace metals. Lead has received the most attention and several studies have examined the physiological and behavioral effects of lead with reference to hyperactivity in children (Needleman et al., 1979: Wessell and Dominski, 1977; David et nl., 1976; Kopito et al., 1969; Kotok, 1972: White and Fowler, 1960). The neurological effects of high dosages of lead have been established, but subtle effects of low dosages are not as numerous (Chattopadhyay er ul., 1977). It has been shown that in hyperactive children lead levels were elevated and inversely related to performance (David er al., 1976). Selenium studies in monkeys have demonstrated behavioral effects with typical signs of brain lesion and lathyrism (Rudra, 1952), and Rosenberg et al. (1966) found that selenium changed the conduction properties of the neural signal. Also chronic cadmium treatment in rats has produced CNS effects, such as decreased medullary serotonin levels, whereas. striatal dopamine and cerebrocortical acetylcholine were significantly 325 0013-9351/81/040325-15$02.00/O Copyright 411 right\
7 1981 by Academic Pra\. Inc. of repmducuon in any form rewrvrd
326
ELY
ET AL.
elevated (Singhal et al., 1976). Cadmium was found to inhibit two catecholamine degradative enzymes in vitro (Revis, 1978). However, the effects of low levels of trace metals on the central nervous system and concomitant behavioral effects specifically in children have not been well studied although the evidence warrants further study (Roels et al., 1980). It is a relatively recent development to examine hair trace element% in specialized groups. One of the first studies in this area showed that zinc supplement administered to zinc-deficient dwarfs increased hair levels of zinc (Prasad, 1966). Reviews of trace elements in hair can be found in Creason et al. (1975), Brown (1974), Eads and Lambdin (1973), and Gordus (1973). Pihl and Parkes (1977) examined the hair content of 14 elements in a group of learning-disabled (LD) children. They reported the following elements were significantly elevated in the LD children: sodium, cadmium, lead, manganese, and chromium. However, in a later report by this group the same measurements were made and the previous significant differences were not found (Pihl et al., 1979). They offer several possible explanations involving potential nutritional and medication changes and the entry into adolescence of many subjects. The objective of the present study is to further examine the relationship between hair trace metals and learning disabilities in children. This project is a substudy of a larger study designed to examine the effects of air pollution on the health of children in Akron, Ohio. We report only on the trace elements in the hair of children and in the air in the immediate vicinity. MATERIALS
AND METHODS
Children in the fourth-sixth grades (ages 9- 12) from two schools (School S and School B) in Akron, Ohio, were requested to participate in the trace metal study which involved analyses of hair trace metals. Of a total of 466 children there were 323 that agreed to participate and comprised the control group. Also there were 77 children in the learning disability (LD) group from the same two schools who participated from a total population of about 100 LD children. The LD children had been evaluated by a multidisciplinary team consisting of a district psychologist and the child’s teacher according to the State of Ohio procedures for evaluating specific learning disabilities (Title 45-Public Welfare, Sections 121a.532 le and 121a.601). Briefly, the LD children functioned within the normal range of intelligence or above (attained IQ above 80), but were below expectancy in one or more of the following areas: oral expression, listening comprehension, written expression, basic reading skills, reading comprehension, mathematic calculation, or mathematic reasoning (achievement 2 standard errors of measurement below the expected level of achievement for his specific ability level). The State definitions of learning disability exclude the mentally retarded, neurological pathology cases, and the emotionally disturbed. Some of the LD children were in special classes, whereas other LD children were in regular classes but had a tutor. The analyses of these subdivisions are presented under Results. Hair samples were collected from each child between October 1976 and April 1977 according to the procedures of the Trace Element Laboratory, Case Western Reserve University, and then sent to that laboratory for analysis of cadmium, arsenic, lead, selenium, and mercury by means of atomic absorption spectroscopy
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
327
(Strain ct al., 1972). The 77 LD children in this study were already in existing learning disability programs. Socioeconomic information was collected on the children’s parents using the Blishen (1967) socioeconomic index and race and medication history were recorded for the children. Aerometric data were collected at the two schools studied. Total suspended particulate (TSP) levels were measured using the high-volume sampling procedure as described in the Federal Register (36:8186, 1971). The stations were operated daily for a 24-hr period beginning and ending at 8:00 AM from October 1977 to June 1978. Each unit had a Sierra Flow controller to maintain flow at 1.13 m3/min. The filter papers were supplied and weighed by a Community Health Assessment Monitoring Program (CHAMP) subcontractor, Stewart Laboratories, Knoxville, Tenn. The trace elements were determined as weekly composites of the filters. The station at School S was located adjacent to the school and along a moderately traveled city street. The station at School B was on top of a IO-ft roof on the school. This school is also bordered on the east by a city street with moderate traffic and is about 4 km from the other school. These two schools and the associated air-monitoring stations are located in a “walking” school district. Ninety-five percent of the students walk to and live within 1 mile of the school. School S is located closer to the known point sources of air pollution in the area. Blood pressure was determined by a licensed medical technician using standard sphygmomanometry (Baumanometer) techniques and a pediatric cuff. The children were at rest in a sitting position and the average of three readings was taken for analysis. The statistical procedures used in this study include analysis of variance, correlation coefficients, Student’s t tests, discriminant function analysis (Wilks), and multiple regression. RESULTS
Table 1 shows the trace metal results of the two groups. Using Student’s t tests it was found that the LD females showed a significant elevation in selenium (P < 0.05) as compared to the control females. Blood pressure analysis showed that the LD females had a lower diastolic blood pressure than control females (P < 0.05). There were no significant group differences between cadmium, lead, mercury. arsenic, or systolic blood pressure. Analysis of the male data shows the same basic trend with cadmium (P < 0.01) and selenium (P < 0.001) significantly elevated in the LD groups as compared to the controls, but in the LD males both systolic and diastolic blood pressure and mercury showed lower values than the controls (P < 0.001). A multiple regression analysis was performed to determine the amount of variance contributed by the metals to blood pressure. In the control males using systolic blood pressure as the dependent variable the five metals only explained 2% of the variance and in the females they explained 8%. For diastolic pressure the metals explained 4% in the control males and 1% in the females. However, in the LD group the metals explained 40% of the systolic pressure variance and 54% of the diastolic variance in the females. In the LD males the metals explained 1 ICC
328
ELY ET AL. TABLE TRACE METALS
FROM
1
HAIR SAMPLES AND BLOOD PRESSURE IN LEARNING CONTROL CHILDREN FROM Two SCHOOLS
DISABILITY
Trace metal (ppm) Group Control Females LD Females Control Males LD Males
Age (years)
N
Pb
9- 12
139
9-12
20
9- 12
184
9-12
57
15.39 + 1.3 11.9 k 1.9 14.27 20.88 16.2 2 1.4
Cd 1.07 kO.10 1.20 co.07 0.97 kO.03 1.13** kO.05
Hg 18.11 21.1 15.9 k0.96 17.0 20.71 14.3* to.62
AND
Blood pressure Se
0.86 kO.10 1.4.5* kO.11 0.73 to.03 1.40*** kO.08
As
(mm Hg)
1.24 to. 12 1.20 *o. 13 1.05 20.06 1.04 50.07
m 2 1.2 64 k 0.8 92* 24.0 58* + 2.7 992 1.0 63 k 0.7 s*** t 1.5 57*** + 1.3
Note. Values are + SE. LD group compared to respective control by sex, Student’s I test: “P < 0 .05., **P < 0.01; ***p < 0.001.
of systolic and 15% of diastolic variance. It was apparent that cadmium and selenium explained most of the variance in the LD group, whereas the metals explained very little of the blood pressure variance in the controls. An analysis of variance of the live elements showed three significant differences between the two groups for each sex (P < 0.01) for cadmium, selenium, and mercury. With regard to blood pressure and metals there was a significant group difference in both males (P < 0.05) and females (P < 0.01) in a two-way interaction between diastolic blood pressure and selenium. In both males and females there was a significant main effect on systolic blood pressure (P < 0.02) between the two groups. In order to examine the data for each school and to correlate aerometric data with hair data in each school we divided the LD and control groups by schools (Table 2). Analysis of this grouping using Student’s t tests showed that LD children in School S had higher levels of cadmium (P < 0.01) and selenium (P < O.OOl), and lower blood pressure (P < 0.01-0.001) than control children in the same school. LD males in School B had higher lead (P < 0.05) and selenium (P < 0.001) levels than control males in the same school. However, these trends were not observed in the LD females of School B. Also in the controls it was found that males in School S had significantly elevated hair lead (P < O.OOl), mercury (P < O.OOl), selenium (P < O.Ol), and systolic and diastolic blood pressure (P < 0.01) as compared to School B controls. The LD children in School S had higher cadmium levels (P < 0.05) and lower blood pressure (P < 0.05) than’LD children in School B. It is interesting that the aerometric data (Table 6) also shows higher air lead, selenium, mercury, and arsenic in School S as compared with School B. Discriminant analysis on all LD children as compared to controls showed that the best discriminators (P < 0.001) were selenium, mercury, cadmium, diastolic blood pressure, arsenic, and sex (Table 3). These variables correctly classified 79.% of the grouped cases. The disctiminant analysis by sex showed that in males the best discriminators (P < 0.001) were selenium, diastolic blood pressure, mercury, and lead which correctly classified 82.9% of the cases. Among the
Note.
9-12
School
LD compared
Y- 12
School LearningS Disability
Values
9- 12
School S Controls
Learning Diability
are *SE.
9912
B
Wears)
Group
School B Controls
Age
CHIL~K~~
TKAC~
19
M
18.5 23.2
17.2 24.4
17.2 21.6
15.1 _f 1.4 13.4 t 1.4
k 1.7
11.5 1-0.83 9.6
***P
14.5
1.33”‘” kO.08
< 0.001.
ro.15
1,4p ..:.
20.09 0.75 so.05 0.82 20.06 ].53^“. to. I7
20.8 18.7 t I.2 19.7 i 1.5 15.0 21.9
? 1.0
l,36v+
14.2
.99 20.04 1.11 k-o.09 1.03 20.06 0.83 20.06 0.94 20.05 I .40’: 20.05 :‘.
Se
0.66 20.03 1.41 20. I4
(ppm)
14.9 20.3 16.3 21.1
Hi?
metal
0.98 to.2
Trace
SCH~OI.
DISABII.IT>
IN EACH
IN LEARNING
COUNTERPARTS
PRESSURE
17.3 + 1.8
1.33 kO.2
Cd
CONI-ROE
-+*P <: 0.01:
THEIR
2
BLOOD
TABLE ES END
17.3 i-2.2
Pb
AND
SAMPI
by sex: *P < 0.05:
6
81
M F
73
F
38
14
F
M
103
M
N
SCHOOL
66
EACH
HAIR
F
Sex
FRO~I
4~ $ FROM
to control
MFI
1.10 -to.10
1.01 20.09 1.03 to.06 1.04 20.06 1.27 20.12
1.04 kO.1 1.16 to.17
1.44 kO.2
As
i a
54. “... &T
.:.:: 2 2
E n 1 F jy
r" 85^” 5 a.:. :/: -+ +-_ 7
z 6 G; >
!i
F
2
iz
g m K 2
662-i
103 + 2
9522 59 2 2 2 106 3 68i-T
9821 62 -c 0.9 k 95 5 -E-t3
9711 ? 95 1
Blood pressure (mm I-k)
330 DISCRIMINANT
FUNCTION ANALYSIS THE MOST SIGNIFICANT
ELY ET
AL.
TABLE
3
(WILKS) VARIABLES
BETWEEN LD AND DISCRIMINATING
CONTROL THE Two
CHILDREN GROUPS
SHOWING
Percentage grouped cases correctly classified
Variable
Wilks h
Significance (P)
Both sexes
Se & Cd BPD As Sex
0.909 0.825 0.769 0.731 0.716 0.703
79.9
Males
Se BPD Hg Pb
0.646 0.623 0.609 0.603
82.9
Females
BPD Se Cd BPS Pb HE?
0.950 0.932 0.831 0.800 0.778 0.760
=0.02 =0.02
80.5
females the best discriminators (P < 0.05) were diastolic blood pressure, selenium, cadmium, systolic blood pressure, lead, and mercury which correctly classified 80.5% of the cases. Within the LD group lead, cadmium, blood pressure, and mercury discriminated correctly between the two schools in 70% of the male cases and 80% of the female cases. Table 4 shows the results of further subdivision of the LD children into those tutored on an individual basis but in a regular class and those in a special all-LD class. There was only one significant group difference in trace metals. Selenium was higher in the special LD class but this was attributed to chance. There were no blood pressure and no significant sex differences within or between groups. When each school was compared to the other using these same LD subdivisions the tutored LD children from School S showed higher levels of lead (P < 0.01) and cadmium (P < O.OS), but lower systolic (86 mmHg vs 95 mmHg, P < 0.05) and diastolic blood pressure (50 mmHg vs 61 mmHg, P < 0.01) than the tutored LD children from School B (n = 13 and n = 28, respectively). This was the same trend as before showing that children from School S have higher trace metal hair content. About 27 of the 77 LD children lived outside the school district; however, there were no significant trace metal or blood pressure differences when they were compared to the resident LD children (Student’s t test). The results of the correlations between hair elements and blood pressure and metal-metal interactions for the five metals are shown in Table 5. There were 20 possible interactions with this combination of variables and 12 of them showed significant correlations in the control group and 6 in the LD group. Cadmium and selenium were inversely related to blood pressure, however, directly related to
TRACE
METALS
IN
LEARNING-DISABLED TABLE
HEAVY METALS DIFFERENT
FROM GROUPS
331
CHILDREN
4 AND BLOOD
HAIR SAMPI.ES OF LEARNING
PRESSURE
DISABILITY Trace
II\;
CHILDREV
metal (ppm) Blood pressure (mm Hg)
Age (years)
Sex
N
Pb
Learning DisabilityTutored School B
9-12
Both
28
12.5 _f 1.8
1.01 kO.07
14.3 50.9
1.2 50.09
1.10 t-O.13
yJz2 61 27
Learning DisabilityTutored School S Learning DisabilityTutored Both Schools
9m 12
Both
13
21.2** k2.9
1.28 to. IO
15.2 k 1.3
1.3 20.15
1.20 -0.13
86- 2 3 5t.F” tZ
9- 12
M
32
16.5 k 1.8
1.06 +0.07
14.6 -to.9
I.? TO.09
1.04 ~0.10
92 z 2 3i-=iT
F
9
M
25
10.8 -c3.2 15.8 22.2
1.20 to.12 1.22 20.07
14.6 2 1.3 14.0 20.9
1.4 kO.16 1.6*’ 20.13
1.40 20.23 1.04 to.09
S=& 28 t 5 yj4-2 57 2 2
F
11
12.7 ~2.3
1.19 io.09
17.0 ~1.3
1.5 kO.16
1.03 +-&I3
9126 58 27
Group
Learning DisabilitySpecial Class Both Schools
9p 12
Cd
Hg
Se
AS
Nofr. Values are zSE. *P r: 0.05. **Pi 0.01.
each other (r = 0.80, P < 0.001 in controls and r = 0.23. P < 0.05 in LDs). It is interesting to note that all the metals were directly related to each other in the controls but only cadmium was strongly correlated with the other metals and blood pressure in the LD group. Table 6 shows the aerometric trace metal results measured from October 1977 TABLE CORRELATION
HAIR
COEFFICIEWTS
ME~AL~METAL
Control SBPP Cd SBP-Se DBP&Cd CdGPb Cd-Hg Cd-Se Cd-As Pb-Hg PbbSe Pb-As Se-Hg Se-As As-Hg Nofr. selenium.
-0.15 -0.13 -0.06 0.50 0.47 0.80 0.54 0.28 0.43 0.32 0.52 0.56 0.35
BETWEEN
INTERACTIONS
5 ME.FALS .*ND BLOOD PRESSURE 4%~ FOR THE Two GROVPS FOR FI\.E METALS HAIR
Level of significance (P)
LD
Level of significance (P)
=0.02 =0.03 N.S.
-0.19 -0.06 -0.25 0. I? -0.31 0.23 0.35 -0.10 -0.01 -0. I’ -0.08 0.03 -0.26
=0.05 N.S. =O.O? N.S. x0.0 I =0.02 =O.OOl N.S. N.S. N.S. N.S. N.S. =O.Ol
SBP = systolic blood pressure, DBP = diastolic Pb = lead. Hg = mercury. As = arsenic,
blood
pressure.
Cd = cadmium.
Se x
332
ELY
ET AL.
TABLE AEROMETRIC
TRACE
METALS
Oct. 1977 B S Nov. 1977 B S Dec. 1977 B S Jan. 1978 B S Apr. 1978 B S May 1978 B S June 1978 B S
Note.
B
School
S
Values
are average
6
FOR 7 MONTHS
Trace
Sampling period and school
Average School
MEASURED
metal
AT EACH
OF THE
SCHOOLS
in air (rig/m?
As
Cd
6.4 10.5
2.5 2.4
1.9 1.0
363 441
1.4 1.5
6.0 10.8
2.3 1.9
1.5 1.1
209 240
1.2 1.8
15.9 12.8
5.2 3.3
1.0 1.3
412 429
2.6 1.6
1.9 5.8
0.1 0.5
0.3 1.8
123 217
0.6 1.0
1.1 9.7
0.5 3.1
0.3 4.4
46 265
0.3 1.1
6.6 6.5
1.3 0.7
1.3 2.1
227 235
2.2 3.2
8.9 8.5
1.6 1.6
1.6 1.3
341 319
2.8 3.6
6.7 24.9 9.2 52.5
1.9 2 1.7 1.9 kl.l
1.1 to.6 1.9 k1.2
246 1134 307 2 94
1.6 kO.9 1.9 + 1.0
Jk
Pb
Se
&SD.
through June 1978. Measures during February and March are missing due to heavy snows and equipment shutdown. There were no significant trace metal differences using Student’s t test between the two schools. However, discriminant function analysis showed that cadmium (P = O.Ol), mercury (P = 0.009), and arsenic (P = 0.13) were significant discriminators between the two schools and correctly predicted 93.8% of the cases. School S had higher values of arsenic and mercury as compared to School B. The trace metals were measured from the total suspended particulate fraction of air (TSP) and analysis of same day TSP samples between the two schools showed no significant difference (School S TSP = 48.7 r&m3 and School B TSP = 45.9 ng/m3), which indicates that the trace metal differences in the two schools were not due just to differences in TSP levels. DISCUSSION
There was a consistency of trace metal values found throughout the data that showed cadmium and selenium elevated in the LD children. This was substan-
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
333
tiated in two different schools located approximately 4 km apart in the Akron, Ohio, area. Also the diastolic blood pressure was consistently lower in the LD children. The lowered diastolic blood pressure in the LD children is difficult to explain. Previous studies have examined the role of cadmium and blood pressure with conflicting results. Recently, Whanger (1979) did not find any relationship between blood or hair cadmium and blood pressure in Oregon residents from different occupations. Cadmium has induced hypertension in mice and rats (Schroeder, 1965: Perry, 1976); however, others have not observed hypertension with cadmium loads in animals (Friberg ef cll., 1971; Porter et LzI., 1974). Since the LD children had higher levels of hair cadmium than controls, and yet lower diastolic blood pressure, the effect appears to be paradoxical. It is possible that behavioral or dietary differences at school and home could have influenced the blood pressure of the LD children. However, analysis of the LD children taking medication (n = 13) which was mostly Ritalin showed that there was no difference in systolic and diastolic blood pressure as compared to LD nonmedicated children (Student’s f test). There also were no significant differences with regard to medication and the trace metals. Racial differences cannot explain the observed differences either, since only 3 LD children were black and there were no significant differences with regard to trace metals or blood pressure between white and black LD children. However, multiple regression analysis showed that in the LD group the metals explained ll- 15% of the male and 40-54s of the female blood pressure variation. This was a severalfold increase in explaining the variance as compared to the controls. This suggests that in the LD females, especially, the metals could be interacting in such a way as to lower peripheral resistance and thereby lower blood pressure. However, the possibility of a centrally mediated mechanism cannot be ruled out due to studies showing cadmium effects on neurotransmitters (Singhal et NI., 1976) and catecholamines (Revis, 1978). A longitudinal follow-up of these children is planned to examine the influence of medication, diet, and behavioral therapies upon trace metals, blood pressure, and learning disability. There was no significant difference between LD and control groups with regard to socioeconomic level (42.2 vs 41.9, respectively). With regard to the elevated cadmium in the LD children a question arises as to the source. Previous studies show that cadmium contaminates the environment through smelting and refining of zinc and lead ores, recovery of scrap metal, combustion of coal and oil, disposal of sewage sludge and waste plastics, battery wastes, electroplating, and phosphate fertilizer contamination (Underwood, 1977: Friberg et nl., 1971; Fleischer ct nl., 1974; Fulkerson and Goeller, 1973). It has been estimated that 58% of the cadmium-consuming industry in the U.S. is located in the Great Lakes states (Fasset, 1972). However, tnere is no reason to believe the LD children were differentially exposed to the trace metals. For smokers the main source of cadmium is through inhalation of cigarette smoke (Underwood, 1977; Shuman et crl.. 1974; Lewis et al., 1972) but for nonsmokers the main source is food followed by air then water, with an average intake of about 20-50 rig/day (Fleischer ef (11.. 1974). However, less than 5% of ingested cadmium is absorbed, the remainder excreted with the feces (Friberget crl., 1971). Hair cadmium content
334
ELY
ET AL.
does appear to reflect exposure to the element. Whanger (1979) found that blood and hair cadmium in Oregon residents was highest in employees of a mine versus offtce workers, smokers versus nonsmokers, and metal workers versus office workers. Body cadmium levels have previously been detected through blood and urine levels, but animal and human studies suggest these are not reliable measures of total cadmium body burden (Carlson and Friberg, 1967; Petering et al., 1973), whereas other studies indicate blood cadmium is a sensitive measure of recent (3 month) exposure (Kjellstrom, 1979). One group found that with heavy cadmium exposure (cadmium salt factory) the blood level of cadmium plateaus after 120 days, whereas urine levels have several complex phases dependent upon dosage and time (Lauweryset al., 1979). Several investigators have successfully used hair as an indicator of the body burden of cadmium (Nordberg and Nishiyama, 1972; Brancato et al., 1976) and others have reported on hair measurements for several trace metals (Hambridge and Droegemueller, 1974; Hammer et al., 1971; Klevay and Hyg, 1973; Maugh, 1978; Petering et al., 1971; Grandjean, 1978). The children in this study were not smokers although we do not have data on the smoking habits of the LD parents. It is possible that parental smoking could affect the children’s hair cadmium level. However, surface contact of hair with smoke should not seriously affect the hair analysis of cadmium since the hair was digested in double-distilled nitric acid and washed thoroughly ten times in doubledistilled water before analysis. To support this contention we did not observe any hair trace metal differences in the control children between those living in “smoking” households and those living in “nonsmoking” households. With regard to selenium sources and effects, the major source is the diet (Underwood, 1977) and selenium disulfide has been found in shampoos and skin medications (Cooper et al., 1974). Water is only a minor source of selenium ranging from 0.1-100 q/liter (Davis and Dewiest, 1966). However, industrial sources of selenium include: glass, pigment, and steel production; rubber curing; and electrolytic copper refining. Physiologically, selenium is deposited in hair, kidney, and liver, and minimally in brain, muscle and fat (Dickson and Tomlinson, 1967; Masson and Young, 1967). The compounds of selenium influence metabolic activities such as oxidative phosphorylation (Wilson and Bandurski, 1956). It also has powerful antioxidant properties (Tappel and Caldwell, 1967) and can bind to: hemoglobin (McConnell and Cooper, 1950), leukocytes (McConnell, 1959), fibrinogen (Celander et al., 1962), and myosin and aldolase in muscle (McConnell and Roth, 1964). Since our data show cadmium and selenium both elevated in the LD children it is interesting to note that recently interactions have been reported between selenium and cadmium. Whanger (1979) showed that selenium decreased the accumulation of cadmium in rat liver and kidney. Also selenium has been reported to limit the binding of cadmium in tissues of the testes, kidneys, and plasma (Chen et al., 1975). The mechanism of action of selenium may be similar to that of cadmium since they both have a propensity for reacting with sulfhydryl groups of proteins (Barron, 1947). It appears that with minimal amounts of selenium present cadmium
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
335
toxicity is reduced. Therefore, the high-selenium hair content in the LD group may be a physiological adaptation to altered cadmium metabolism. The subject of long-term health effects specifically of these two metals have been reviewed in a number of reports and symposia (Friberg e1 crl., 1971; Fleischer et ul., 1974: Fulkerson and Goeller, 1973; Muth er nl., 1967: Kovaliskii and Ermakov, 1970: and Zingaro and Cooper, 1974). It is interesting to compare our results with those of Pihl’s laboratory (original investigator in this area) since we both used the same trace element laboratory to analyze our hair samples (Trace Element Laboratory, Case Western University). Although very little data exist on learning disability and trace metals, Pihl (1975) has thoroughly reviewed the area and his laboratory showed in 1977 that there were strong correlations between LD children and specific trace metals. In their original study cadmium, cobalt, manganese, chromium, and lithium separated the control and LD groups in a discriminant analysis with 97.5% accuracy (Pihl and Parkes, 1977). However, in a follow-up study about 2 years later there was no significant discrimination between the two groups mainly because the LD group values returned toward control baseline (Pihl et ml., 1979). They suggested that these element changes could be due to treatment of the LD group with medication, dietary changes, behavioral therapies, and aging effects. Our value of elevated cadmium in the LD group (1.16 ppm) is lower but in general agreement with the elevated cadmium levels in their original LD groups (1.72 ppm), and our control values are similar (0.94 vs 1.08 ppm, respectively). Our elevated selenium values and blood pressure results cannot be compared because they were not measured in Pihl’s studies. One objective of our study was to determine the trace metal content of the air the children were breathing in order to determine if this was an important source. Our data suggest that the air trace metals in the study area were not elevated as compared to other cities, but there were correlations between trace metal content of the air and hair. However, it should be noted that the aerometric data were collected about one year after the hair samples. We do not believe that this invalidates the results because in our continuous monitoring of the air at these two locations there has been minimal variation over a 2-year period when the same months are compared. Schroeder (1970) has reviewed the data on the concentration of cadmium in the air of the United States and gives a range of cadmium in urban areas of 2-370 r&m” and 0.4-26 ng/m3 for nonurban areas. Other areas in Ohio have been reported by Lee et nl. (1968) as follows: Cincinnati downtown, 80 rig/m” : and Fairfax (suburban), 20 rig/m”. Athanassiasdis ( 1969) reported a maximum of 130 ngim3 in 1960 for Akron, Ohio. However, recently the air in Akron has become cleaner with better air pollution controls and reduced industry. Our values show a range of 0. l- 5.2 ng/m3 of cadmium in Akron which is very low compared to the NIOSH recommendation of 40 ng/m3 (Fairchild et trl., 1977). Also the aerometric levels of lead and selenium were relatively low in our study areas. It does not appear that the air is a main source of trace metal exposure for the children in our study area. However, in School S with the highest air lead, mercury, and selenium the children (LD and control) reflected higher hair levels of these same elements than children in School B which indicates an association
ELY ET AL.
336
between aerometric and hair trace metal levels. The interactive effects of low levels of trace metals upon CNS function and the explanation for the LD differences remain to be determined. The subtle neurologic effects of chronic low-grade lead poisoning concern many because of the strong possibility of its connection to the 10% or more children suffering from learning disabilities. Needleman et al. (1979) in a tightly controlled study found deficits in psychologic and classroom performance of children (first and second grades) associated with elevated dentine lead levels. The deficits were apparent in general intelligence scales, verbal subtests, and auditory- or speech-processing tests. This study suggests that chronic exposure to low lead levels (below 30 pg/dl blood standard) may lead to central nervous system alterations. Numerous studies suggest that moderate elevations of blood lead (40-70 pg/lOO cc) are an important factor in producing significant impairment in cognitive, verbal, perceptual, and fine motor skills when compared to a control group with levels below 30 pg/lOO cc (Perrino and Erphart, 1974; Landrigan et al., 1975; de la Burde and Choate, 1975). Although our studies did not show consistently elevated lead levels in the LD children the results did show that in the school with highest air lead concentration the LD children showed higher lead levels than the controls in the same school. If these LD children were exposed to the same air, water, and dietary levels of trace metals, then there appears to be a metabolic difference in the handling of the trace metals. It is not possible from our data to suggest a cause-effect relationship between learning disability and trace elements, but the data from two different laboratories now indicate that the effects of trace elements on learning disability and behavioral effects should be further examined in longitudinal studies. ACKNOWLEDGMENTS The authors would like to express appreciation to the following people for their contribution to this study: the principals of the two schools involved, Mrs. Scholl and Mrs. Dann; the students involved in the study; and Mary Begley for typing the manuscript. This research was supported under EPA Grant 80425601, 02.
REFERENCES Athanassiadis, Y. C. (1969). Air Pollution Aspects of Cadmium and Its Compounds. U.S. Clearinghouse Fed. Sci. Techn. Inform. PBl88, 086, pp. l-77. Barron, E. S. (1947). Inhibition of succinic oxidase by heavy metals and its reactivation with dithiols. Biochem.
J. 41, 346.
Blishen, B. (1967). A socio-economic index for occupations in Canada. Canad. Rerr. Sot. Anthrop. 4, 41-53. Brancato, D. J., Picchioni, A. L., and Chin, L. (1976). Cadmium levels of hair and other tissues during continuous cadmium intake. J. Toxicol. Environ. Health 2, 351-359. Brown, A. C. (1974). “The First Human Hair Symposium.” Medcom Press, New York. Carlson, L. A., and Friberg, L. (1967). The distribution of cadmium in blood after repeated exposure. Stand. J. Clin. Lab. Invest. 9, l-4. Celander, D. R., Jaguo, M., and Naschke, M. D. (1962). Biosynthetic labelling of fibrinogen and other proteins with radioselenium. Fed. Proc. 21, 36. Chattopadhyay, A., Roberts. T. M., and Jervis, R. E. (1977). Scalp hair as a monitor of community exposure to lead. Arch. Environ. Health 32, 226-236. Chen, R. W., Whanger, P. D., and Weswig, P. H. (1975). Selenium-induced redistribution of cadmium binding to tissue proteins: A possible mechanism of protection against cadmium toxicity. Bioinorg. Chem. 4, 125.
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
337
Cooper, W. C., Bennett, K. G., and Croxton, F. C. (1974). The history. occurrence. and properties of selenium. In “Selenium” (R. A. Zingaro and W. C. Cooper. Eds.). Van Nostrand-Reinhold. Princeton, N.J. Creason J. P., Hinners. T. A.. Bumgartner, J. E., and Pinkerton. C. ( 1975). Trace elements in hair as related to exposure in metropolitan New York. Clin. Cl~rm. N. l’. 21. 603-612. David, 0.. Hoffman, S. P.. Sverd, J.. Clark, J., and Voeller K. (1976). Lead and hyperactivity. Behavioral response to chelation: A pilot study. Amer. ./. Psyc-lriut. 133, 1155- 1158. Davis. S. N.. and Dewiest, R. J. M. (1966). “Hydrogeology.” Wiley. New York. de la Burde, B.. and Choate, M. S. (1975). Early asymptomatic lead exposure and development at school age. J. P~dicrr. 87, 638-641. Dickson, R. C.. and Tomlinson. R. H. (1967). Selenium in blood and human tissues. Cliff. C/ii/jr. Ac./o 16. 311. Eads, E. A., and Lambdin. C. E. (1973). A survey of trace metals in human hair. t‘n\~ir~~n. Kcs. 6. 247-252. Fairchild, E. J.. Lewis. R. L., and Tatken, R. L. (Eds.) (1977). “Registry ofToxic Effects ofchemical Substances,” Vols. 1 and II, U.S. Dept. HEW, Cincinnati. Fassett, D. W. (1972). Cadmium. In “Metallic Contaminants and Human Health” (D. H. K. Lee. Ed.), pp. 97- 124. Academic Press, New York. Fleischer. M., Sarofin. A. F., Fasset. D. W., Hammond, P., Shacklette. H. T.. Nisbet. I. C. T.. and Epstein, S. (1974). Environmental impact of cadmium: A review by the panel on hazardous trace substances. Ent~iron. Heulth Pc~rsp~ci. 7, 253-323. Fleming. G. A.. and Walsh, T. (1957). Selenium occurrence in certain Irish soils and its toxic effect in animals. Proc.. Roy. Irish Acud. Sect. B 58, 151. Friberg, L. (1950). Health hazards in the manufacture of alkaline accumulators. with special reference to chronic cadmium poisoning. Actor Med. Scrrncl. 138, Suppl. 240. Friberg. L.. Piscator. M.. and Nordberg. G. (1971). ‘*Cadmium in the Environment.” Chem. Rubber Pub. Co.. Cleveland. Fulkerson, K., and Goeller. H. E.. Eds. (1973). “Cadmium: The Dissipated Element.” Oak Ridge National Laboratory Pub. No. ORNL NSF EP 21, Oak Ridge, Tenn. Gordus. A. (1973). Factors affecting the trace-metal content of human hair. J. Rrldiorrrrul. Chum. 15. 229.-243. Grandjean, P. (1978). Lead concentration in single hairs as a monitor of occupational lead exposure. fnr. Arc~lz. Ckwp. Envitm. H~rrlth 42, 69-82. Hambridge. K. M.. and Droegemueller. W. (1974). Changes in plasma and hair concentrations of zinc. copper. chromium. and manganese during pregnancy. Ohstc,r. C;~nc,c~o/. 44. 666-672. Hammer. D. I.. Finklea. J.. Hendricks, R., Shy, C., and Horton, R. (1971). Hair trace metal level\ and environmental exposure. Amer. J. Epidemicd. 93, 84-92. Kjellstrom, T. (1979). Exposure and accumulation of cadmium in populations from Japan. the United States. and Sweden. Enl~iron. Health Perspect. 28, 169- 197. Klevay. L. M.. and Hyg, S. V. ( 1973). Hair as a biopsy material. Avt,ll. E/r\,irott. Hrtrlrh 26, 169- 172. Kopito. L.. Briley. A. M.. and Schwachman. H. (1969). Chronic plumbism in children. Amc,,-. .Zlr,c/. A .YSO~~. 209. 243 - 248. Kotok. D. (1972). Development of children with elevated blood lead levels: a controlled study. .1. I’(,t/. 80. 57-61. Kovaliskii. V. V.. and Ermakov, V. V. (1970). “The Biological Importance of Selenium.” National Lending Library for Science and Technology (Publisher), Yorkshire. Landrigan. P. J.. Baloh, R. W.. Barthol, W. F., Whitworth, R. H., Staehling. N. W., and Rosenbloom. B. F. (1975). Neurophyschological dysfunction in children with chronic low-lead level lead absorption. Lancef 1, 708-712. Lauwerys. R.. Roels. H.. Regniers, M., Buthet. J. P., Bernard, A., and Goret, A. (1979). Significance of cadmium concentration in blood and in urine in workers exposed to cadmium. Eursirorr. Rev. 20. 375-379. Lee. R. E.. Jr.. Patterson, R. K.. and Wagman, J. ( 1968). Particle-size distribution of metal compctnents in urban air. Environ. Sc,i. Te~hnol. 2, 288. Lewis. G. P., Jusko, W. J.. Coyghlin, L. L., and Hartz, S. (1972). Cadmium accumulation in man: Influence of smoking, occupation, alcoholic habit, and disease. .I. Chuo/~ic~. Div. 25. 717-726.
338
ELY ET AL.
Masson, K. E., and Young, J. 0. (1967). in “Selenium in Biomedicine” (0. H. Muth, Ed.), pp. 383-394, Avi Pub. Co., Westport, Conn. Maugh, T. H. (1978). Hair: A diagnostic tool to complement blood serum and urine. Science 202, 1271- 1273. McConnell, K. P. (1959). Selenium-75 binding in dog leukocytes. Texas Rep. Biol. Med. 17, 120. McConnell, K. P., and Cooper, 3. I. (1950). Distribution of selenium in serum proteins and red blood cells after subcutaneous injection of sodium selenate containing radioselenium. J. Biol. Chem. 183, 459. McConnell, K. P., and Roth, D. M. (1964). Selenium in rabbit skeletal muscle myosin. Fed. Proc. 20, 2990. Muth, 0. H., Oldfield, J. E., and Weswig, P, H., Eds. (1967). “Selenium in Biomedicine.” Avi Pub. Co., Westport, Conn. Needleman, H. L., Gunnoe, C., Leviton, A., Reed, R., Peresie, H., Maher, C., and Barrett, P. (1979). Deficits in psychologic and classroom performance of children with elevated dentine lead levels. N. Engl.
.I. Med.
300, 689-695.
Nordberg, G. F., and Nishiyama, K. (1972). Whole body and hair retention of cadmium in mice. Arch. Environ.
Health
24, 209-214.
Perrino, J., and Erphart, C. (1974). The relation of subclinical lead level to cognitive and sensorimotor impairment in black preschoolers. J. Learn. Disabil. 7, 26-30. Perry, H. M. (1976). Review of hypertension induced in animals by chronic ingestion of cadmium. In “Trace Elements in Health and Disease” (A. S. Prasad, Ed.), Vol. II, p. 417. Acad. Press, N.Y. Petering, H. G., Yeager, D. W., and Witherup, S. 0. (1971). Trace metal content of hair. Arch. Environ.
Health
23, 202-207.
Petering, H. Cl., Yeager, D. W., and Witherup, S. 0. (1973). Trace metal content of hair. II. Arch. Environ.
Health
27, 327-330.
Pfeiffer, C. C. (1975). “Mental and Elemental Nutrients.” Keats, New Canaan, Conn. Pihl, R. 0. (1975). Learning disabilities and intervention programs in the schools. In “Progress in Learning Disabilities” H. R. Myklebust, Ed.), Vol. III, pp. 10-28. Grune & Stratton, New York. Pihl, R. O., and Parkes, M. (1977). Hair element content in learning disabled children. Science 198, 204- 206. Pihl, R. O., Parkes, M., and Stevens, R. (1979). Nonspecific interventions with learning disabled individuals. In ‘*Rehabilitation, Treatment, and Management of Learning Disorders.” (R. M. Knights and D. J. Bakker, Eds.). Univ. Park Press, Baltimore. Porter, M. C., Miya, T. S., and Bousquet, W. F. (1974). Cadmium: Inability toinduce hypertension in the rat. Toxicol. Appl. Pharmacoi. 27, 692. Prasad, A. (1966). Metabolism of zinc and its deficiency in human subjects. In “Zinc Metabolism” (A. Prasad, Ed.). Thomas, Springfield, III. Revis, N. (1978). A possible mechanism for cadmium-induced hypertension in rats. Life Sci. 22, 479-488. Roels, H. A., Buchet, J. P., Lauwerys, R. R., Braux, P., Claeys-Thoreau, F., Lafontaine, A., and Verduyn, G. (1980). Exposure to lead by the oral and the pulmonary routes of children living in the vicinity of a primary lead smelter. Environ. Res. 22, 81-94. Rosenberg, P., Mantner, H. G., and Nachman, S. D. (1966). Similarity of effects of oxygen, sulfur, and selenium isologs on the acetylcholine receptor in excitable membranes ofjunctions and axons. Proc.
Nat.
Acad.
Sci. USA,
55, 835.
Rudra, M. N. (1952). Toxic principle of lathyrus sativus. Nature (London) 170, 125. Schroeder, H. A. (1965). Cadmium as a factor in hypertension. 1. Chronic Dis. 18, 647-656. Schroeder, H. A. (1970). A sensible look at air pollution. Arch. Environ. Health 21, 798. Shuman, M. S., Voors, A. W., and Gallagher, P. N. (1974). Contribution of cigarette smoking to cadmium accumulation in man. Bull. Environ. Contam. Toxicol. 12, 570-576. Singhal, R. L., Merali, Z., and Hrdina, P. D. (1976). Aspects of the biochemical toxicology ofcadmium. Fed. Proc. 35, 75-79. Strain, W. H., Pories, W. J., Flynn, A., and Hill, 0. A. (1972). Trace element nutriture and metabolism through head hair analysis. In “Trace Substances in Environmental Health” (D. Hemphill, Ed.). Univ. of Missouri Press, Columbia.
TRACE
METALS
IN
LEARNING-DISABLED
CHILDREN
339
Tappel. A. L.. and Caldwell, K. A. (1967). In “Selenium in Biomedicine (0. H. Muth, Ed.). pp. 345-361. Avi Pub. Co.. Westport, Conn. Underwood. E. J. (1977). “Trace Elements in Human and Animal Nutrition.” 4th ed. Academic Press. New York. Wessel, M. A.. and Dominski, A. (1977). Our children’s daily lead. Amer. Ci. 65, 294-298. Whanger. P. D. (1979). Cadmium effects in rats on tissue iron. selenium, and blood pressure: blood and hair cadmium in some Oregon residents. Etlt~irotz. Herrlth Pcrspec~t. 28, 115% 121. White. H. H. and Fowler, F. D. (1960). Chronic lead encephalopathy. Pctliclr. 25. 309-315. Wilson. L. G., and Bandurski. R. S. (1956). An enzymatic reaction involving adenosine triphosphate and selenate. Arch. Biochem. Bioplzys. 62, 503. Zingaro. R. A.. and Cooper, W. C. (Eds.) (1974). “Selenium.” Van Nostrand-Reinhold. Princeton. N.J.