EPA-600/1-77-037
June 1977
Environmental Health Effects Research Series
            STUDIES IN  SUBCLINICAL LEAD  EXPOSURE
                                               Health Effects Research Laboratory
                                              Office of Research and Development
                                             U.S. Environmental Protection Agency
                                       Research Triangle Park, North Carolina  27711

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                                  EPA-600/1-77-037
                                  June 1977
 STUDIES IN SUBCLINICAL LEAD EXPOSURE
                  by
         Herbert L. Needleman
The Children's Hospital Medical Center
         300 Longwood Avenue
     Boston, Massachusetts  02115
       Contract No. 68-02-1239
           Project Officer

            Warren Galke
      Population Studies Division
  Health Effects Research Laboratory
  Research Triangle Park, N.C. 27711
 U.S. ENVIRONMENTAL PROTECTION AGENCY
  OFFICE OF RESEARCH AND DEVELOPMENT
  HEALTH EFFECTS RESEARCH LABORATORY
  RESEARCH TRIANGLE PARK, N.C. 27711

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                           DISCLAIMER

     This report has been reviewed by the Health Effects  Research
Laboratory, U.S. Environmental Protection Agency,  and  approved  for
publication.  Approval does not signify that  the contents necessarily
reflect the views and policies of the U.S. Environmental  Protection
Agency, nor does mention of trade names or commercial  products
constitute endorsement or recommendation for  use.
                                11

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                               FOREWORD

     The many benefits of our modern, developing, industrial society are
accompanied by certain hazards.  Careful assessment of the relative risk
of existing and new man-made environmental hazards is necessary for the
establishment of sound regulatory policy.   These regulations serve to
enhance the quality of our environment in order to promote the public
health and welfare and the productive capacity of our Nation's population.

     The Health Effects Research Laboratory, Research Triangle Park,
conducts a coordinated environmental health research program in toxicology,
epidemiology, and clinical studies using human volunteer subjects.  These
studies address problems in air pollution, non-ionizing radiation,
environmental carcinogenesis and the toxicology of pesticides as well as
other chemical pollutants.  The Laboratory develops and revises air quality
criteria documents on pollutants for which national ambient air quality
standards exist or are proposed, provides the data for registration of new
pesticides or proposed suspension of those already in use, conducts research
on hazardous and toxic materials, and is preparing the health basis for
non-ionizing radiation standards.  Direct support to the regulatory function
of the Agency is provided in the form of expert testimony and preparation of
affidavits as well as expert advice to the Administrator to assure the
adequacy of health care and surveillance of persons having suffered imminent
and substantial endangerment of their health.

     One of the major pollutants of interest to the Health Effects
Research Laboratory is lead.  In particular, the health impact of
low level lead exposure is of much current concern.  This report
covers the findings of an epidemiologic study of the neuropsychologic
effects of low level lead toxicity.  Evidence is presented suggesting
that increased levels of lead in the body of children may result in
decreased attention span and impaired perceptual motor function.
                                               H.  Knelson, M.D.
                                               Director,
                                   Health Effects  Research Laboratory
                                  iii

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                                    ABSTRACT
     This study was initiated to examine the utility of neuropsychologic
testing in identifying deficits in children with asymptomatic elevations in
blood lead levels.

     From the files of the Boston Lead Screening Project we selected black
male children between the ages of six and eight years of age, considered asympto-
matic for lead toxicity who had blood lead tests recorded between the ages of
1 1/2 and 5 years of age.  High lead subjects were children with one or more
blood lead levels greater than 50ug/dl.  Low lead subjects were children with no
blood lead level greater than 30ug/dl.

     Forty-one high lead and 35 low lead subjects were tested by a battery of
neuropsychologic tests measuring intelligence, verbal performance, visual
motor performance, gross and fine motor function, and attention span.  Other
covariates measured were socioeconomic status, birthweight, and medical history.
Seventeen high lead and 17 low leadsubjects were excluded from data analysis
because their medical history revealed either prematurity, significant head
injury  or other illness.  The 24 high lead and 16 low lead males were similar
with respect to age at time of testing, SES, and birthweight.

     High lead children were consistently slower at each block of trials on
the Reaction Time under Varyinc Conditions of ^elay (a measure of attention),
and performed significantly less well on Subtest I of the Frostig Battery.
High lead subjects tended to perform less well on the Maze Coordination Test,
and on the Tactile Form Recognition Test with the non-dominant hand.
                                       IV

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                              CONTENTS
F'oreword	ill
Abstract	iv
Acknowledgment	vi

     1.  Conclusions and Recommendations 	   1
     2.  Experimental Procedures 	   2
              Study Sample	   2
              Subject Ascertainment  	   2
              Figure I	   3
              Outcome Data	   4
     3.  Results and Discussion  .	   7
              Tables I-IV	8-11
References	14
Appendices

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                             ACKNOWLEDGEMENTS
     The generous cooperation of the Boston Lead Screening Project, directed
by Mr. Ron Jones, and the Massachusetts Lead Poisoning Control Program,
Dr. Robert Klein, Director, who made their files available to us, is grate-
fully acknowledged.

     Mrs. Janice Adams was responsible for searching 20,000 subject cards
in the Boston Lead Screening file, identifying, contacting and testing
subjects, and played a major part in the data analysis.  I wish to especially
acknowledge her tireless and careful work.
                                     vi

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                                   Section 1

                         CONCLUSIONS & RECOMMENDATIONS
     Black male children with blood lead levels measured at a mean age of
48 months greater than 50ug/100ml differed significantly from children
similar with respect to sex, age, birthweight, and socioeconomic status but
with a blood lead of 30ug/100ml on two neurobehavioral measures: reaction
time under conditions of varying delay (a measure of attention) and Test I
of the Frostig Battery (eye-hand coordination).  High lead children also did
less well on Maze Coordination, another measure of eye-hand coordination, and
Tactile Form Recognition.

     The sample size of this study and the small number of positive findings
limits the ability to generalize from these results.  The differences in eye-hand
coordination and attention are in support of other studies of low level lead expo-
sure in children (1,4,5,8,19,20).  Future studies of larger numbers of children
with low level lead exposure concentrating on indices of attention and eye-hand
coordination are warranted.

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                                   Section 2

                            EXPERIMENTAL PROCEDURES
Study Sample

High Lead—

     Black, male children, age 6-8 years, with blood lead levels > 50ug/100ml
when screened between the ages of 1 1/2 to 5 years, but no history of lead
encephalopathy.

Low Lead Controls—

     Black, male children, age 6-8 years, with blood lead levels < 30ug/100ml
when screened between the ages of 1 1/2 to 5 years.

     All children were obtained from the register of the Boston Lead Screening
Program, Boston City Hospital.

Subject Ascertainment

     The Lead Poisoning Prevention Center made its files available to us on
February 6, 1974.

     The files contained approximately 18,000 low lead  (<50ug/g) and 2,000
high lead  (>50ug/g) individuals.  The following 10 months  (February 1974 to
September 1974) were spent extracting possible subjects, contacting them, and
testing subjects.  All 20,000 cards were individually checked.  A total of 386
low lead subjects and 175 high lead subjects were identified.  Subjects were
tested from September 1973 to February 1975.

     Contacting subjects was a major problem.  Phones were not listed in the file
for 79 controls and 41 high lead children (Figure I).  Thirty percent of the
control group and 38% of the high lead group whose phones were listed in the
file had been changed to unpublished numbers.  This in itself limited our
population since in some cases it was the only way that race could be tactfully
determined.  We were finally able to reach 80 controls and 54 high lead subjects
by phone.  Nineteen percent of these controls and 22% of these high lead subjects
refused to join the study.  Thirty-eight percent of these controls and 52% of these
high lead subjects accepted by phone.

     A total of 212 (122 control and 90 high lead) first contact letters (see
enclosure)  with enclosed, self-addressed, stamped postcards were sent.

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                                    Figure I

                             Subject Ascertainment
20,000 Subjects.
               t
(LPC File)      I
 Eligible Subjects:
_, Black Males Age 6-8 Yrs. in  1974
 iwith Blood Leads> 50ug at Age 1 1/2 -  5 Years
 or with Blood Leads < 30ug at Age  1 1/2 -  5 Years
                      Phone
                      Contact
Yes No Mail Contact
54 HL

80 LL



90 HL

122 LL
            Agreed
                                Answer
NO
26 HL
50 LL
Yes Yes No

28 HL
30 LL

15 HL
22 LL

178 Subjects

                           Kept Appt.
(Broke 2 or more) No Yes


2 HL
17 LL


41 HL
35 LL
                                      Suitable
                                        for
                                   Data Analysis
       (Confounding
        Variables)
No Yes
17 HL
17 LL


24 HL
18 LL

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Twenty-two controls and 15  high leads   accepted by return card.  Only one
control and 4  high leads   refused by return card.  Follow-up letters were
sent to non-respondants.  Twenty-three percent of all letters were returned
with no forwarding address.  Subjects who cancelled their appointments more
than twice were excluded.

     From this total population we tested 35 control subjects and 41  high
lead   subjects.  After testing, 17  high lead   and 17 controls were excluded
because of additional information the parents disclosed, such as prematurity,
head injuries, or other confounding variables.
Outcome Data

Maternal History—

     Each mother at the time the child    received the neuropsychological
profile, completed a health questionnaire (Appendix I).

Neuropsychological Battery—

     Each child received the following neuropsychological battery:

     Peabody Picture Vocabulary Test (14)—This test assesses vocabulary
recognition by the use of pictures.  Subject must choose one out of four
pictures presented which best portrays the stimulus word.  The stimulus
words are arranged in order of increasing difficulty.  Testing proceeds until
six errors out of eight trials are obtained.  Mental age, percentile score and
IQ are computed from the raw score.  Raw score = total answered minus number
of errors.

     Lincoln Oseretsky Motor Development Scale (15)—A shortened form employing
12 performances testing fine and gross motor function is employed.  Each item
is scored from 0 to 3, and a total score calculated.

     Reaction Time under Varying Conditions of Delay (16)—This is a test of
the ability to attend to a ready signal after varying periods of delay, and
is one index of the subject's attention span.  Subject is required to respond
to an auditory stimulus by depressing a key after a ready signal is given.
Four blocks of six trials each are given at 3, 12, 12, and 3 second ready
periods.  Means and standard deviations are calculated for each block.

     Visual Motor Integration Test (12)—This is a test-of perceptual function
in which the subject must copy (with paper and pencil) geometric forms of
increasing complexity.  A mental age score is computed for each subject from
standardized score sheets.

     Frostig Developmental Test of Visual Perception (13)—This is a test of
three operationally defined perceptual functions:  (I) the ability to coordinate
vision with hand movements; (IV) perception of an object in relation to the
observer; (V) perception of the position of two or more objects in relation
to each other.

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          I.  Eye-Motor Coordination; Subject draws continuous straight, curved,
or angled lines between boundaries of various width, or from point to point
without guidelines.

          IV.  Position in Space: Subject makes discriminations of reversals
and rotations of common objects presented in a series.

          V.  Spatial Relationships; Subject copies lines of various lengths
and angles using dots as guide points.

     A standard score for each subject is computed from raw scores.

     Illinois Test of Psycholinguistic Abilities (17)—This is a test of commu-
nicative skills, measuring the capacity to receive, interpret, and transmit
information through auditory, vocal, and visual motor channels.

          1.  Verbal Expression; Subject describes verbally four simple stimulus
objects.  Number and category of responses are coded.

          2.  Manual Expression;  Subject demonstrates manually the use of a
standard series of pictured objects.  Number and category of responses are
coded.

          3.  Auditory Closure; Examiner presents a series of words with certain
sounds omitted.  Subject must respond with the completed word.

          4.  Sound Blending; E presents successive sounds of words or nonsense
words with a distinct break between the sounds.  Subject is asked to verbalize
the whole word.

     Elements of the Halstead Reitan Battery  (18)—Eleven items of this broad
neuropsychologic assessment battery were selected which were not redundant to
other tests in our profile, and which tested motor function, cerebral dominance,
and haptic-kinesthetic performance.

          1.  Lateral Dominance;  Subject is asked to perform 4 or 5 simple
motor tasks.  Dominance is determined.

          2.  Right-Left Discrimination; Subject is asked to discriminate
right and left on himself and then on a cardboard figure of a child.

          3.  Finger Oscillation Test; Measures finger-tapping speed, using
the index finger.

          4.  Tactile Performance Test;  Blindfolded the subject is asked to
fit wooden blocks into their proper spaces on the fortnboard provided, with
dominant hand, non-dominant hand, and then both hands.  S is asked to recall
shapes and  location of blocks.

          5.  Tactile Form Recognition;  S is asked to identify the shape
 (circle, square, triangle, cross) of a small plastic chip without seeing it.

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          6.  Tactile Finger Recognition;  S must identify individual fingers
after tactile stimulation without the use  of vision.

          7.  Fingertip Writing Perception; S must report without the use of
vision whether an X or an O was written on his fingertip.

          8.  Maze Coordination; S is required to move a stylus through a
vertical maze without touching the sides.   Number of touches and total time
against the side is recorded electroribally.

          9.  Groove Steadiness; S must move a stylus up and down a vertical
groove without touching the sides.  Number and time of touches is recorded.

          10.  Steadiness Test; S must hold a stylus in a hole without touching
the sides.  Four successively smaller holes at 15 seconds per hole.  Number
and time of touches is recorded.

          11.  Grooved Pegboard;  S must put small metals pegs into a pegboard
as fast as he can.  Each peg is keyed so that its orientation must be precisely
adjusted in order to be inserted.

     Raw scores for each subtest were computed.

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                                   Section 3


                             RESULTS AND DISCUSSION
Data Analysis

     Because of the small sample size and because the outcome measures did not
appear to be normally distributed, non-parametric tests of ranks (Mann Whitney-
U) were applied to the psychological data.  One tailed test of significance was
chosen because the direction of effect was expected to favor low lead subjects.

     All children included in the analysis (24 high leads and 18 controls) were
Black males.  The two groups were similar with respect to age at time of testing,
socioeconomic status, and birthweight.

                          Mean Age         Mean Socioeconomic           Mean
                         at Testing        	Status*	        Birthweight

        High Lead        78.6±6.4                4.4±.6              3.44±.46kg

        Low Lead         79.9±6.8                4.6±.5              3.37±.43kg

                    *Hollingshead's Two Factor Index of Social Position


     No significant differences were found between high and low lead groups on the
Visual Motor Integration Test, Frostig subtests IV and V, Peabody Picture Vocabulary
Test, Illinois Test of Psycholinguistic Abilities, and subtests of the Halstead
Reitan Battery (Tables I-IV).

     High lead children did significantly poorer on subtest I of the Frostig
Battery, a test which measures eye-hand coordination.

     High lead children were consistently slower to respond to the onset
stimulus on the reaction time test in each block of trials (Table II).  The
differences were most marked in blocks 3 and 4, but only reached significance
in block 4  (3 second delay).  This is consistent with the hypothesis that the
children were unable to attend closely to the stimulus under conditions of
longer delay, or after 10 minutes at a boring task.

     High lead children did less well at the Maze Coordination Test, but this
difference did not reach significance.  They also tended to perform less well
with the non-dominant hand on Tactile Form Recognition.

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                                        TABLE I

           Meuropsychological Outcome Measures in High and Low Lead Children

Test
Visual Motor
Integration


HL
LL

N
23
16
Median
Score
-13.5
-14.5

Range
34
32

_U_
209

0.71
                                                          .24
                                                                        Remarks
     Units are difference
     in months between
     achieved and standard
     score.
Frostig
I - HL
LL
IV HL
LL
V HL
LL

23
15
23
15
23
15

8.8
,10.5
9.9
9.3
9.1
9.0

7
8
8
7
5
8
                                            109   -1.90   .03   Units are scale scores,
                                            196    0.72    NS
                                            170   -0.07    NS
Peabody
Picture Vocab.

Lincoln-
Oseretsky
HL
LL
HL
LL
24
16
22
16
53.0
59.5
38.5
38.5
96
86
30
23
                                            183   -0.25
                                            200
0.71
        NS   Units are percentiles,
NS   Units are raw scores.
                                                      (One-tailed test of significance)

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                             TABLE II

Neuropsychological Outcome Measures in High and Low Lead Children

Test
Reaction Time
Block 1
(3 sec. delay)
Block 2
(12 sec. delay)
Block 3
(12 sec. delay)
Block 4
(3 sec. delay)
Illinois Test of
Psycholinguistic
Abilities
Verbal

Manual

Auditory
Closure
Sound
Blending



HL
LL
HL
LL
HL
LL
HL
LL



HL
LL
HL
LL
HL
LL
HL
LL

N

22
15
22
15
19
14
18
14



23
14
23
16
22
13
22
13
Median
Score

363
340
475
450
570
495
460
385



38
37
42.5
38.5
35.5
32.8
43.5
37.5

Range

660
340
640
500
650
360
430
230



29
21
28
20
17
11
33
32

U

181.0

159.5

149.0

174.0




154.0

222.0

177.0

176.0

                                                 0.49
                                                -0,19
                                                -0.22
                                                 1.08
NS
NS
                                                 0.58    NS
                                                 1.82     .03
NS
NS
                                                                  Remarks
Score is in
milliseconds.
Units are
scale scores,

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                            TABLE III

Neuropsychological Outcome Measures in High and Low Lead Children

Test
Finger Tapping
Dominant Hand

Non-Dominant

Tactile
Performance
Tactile Form
Recognition
Dominant

Non-Dominant

Fingertip
Writing
Dominant

Non-Dominant

Tactile Finger
Recognition
Dominant Hand

Non-Dominant




HL
LL
HL
LL
HL
LL


HL
LL
HL
LL


HL
LL
HL
LL


HL
LL
HL
LL

N

23
12
23
12
12
7


23
16
23
16


23
16
23
16


23
16
23
16
Median
Score

41.6
41.0
35.6
34.5
-163.0
-164.0


25.5
25.6
23.5
23.5


9.77
9.61
9.90
9.83


7.36
7.25
6.38
6.90

Range U z

22 127.5 -0.36
13
24 157.0 0.66
18
1173 44.0 0.18
554


21 165.0 -0.54
18
18 134.0 -1.43
17


3 209.0 0.71
5
5 197.0 0.37
5


8 182.0 -0.06
7
8 165.0 -0.54
8

_E_

NS

NS

NS



NS

NS
.07


NS

NS



NS

NS

                                                                   Remarks
                                                              Units are mean # of
                                                              taps - 5 trials of
                                                              10 sec. each.
                                                              Units are deviation
                                                              in seconds from stan-
                                                              dard score.
                                                              Units are in seconds
                                                              sum of 2 trials/hand
                                                              Units are # of
                                                              correct choices.
                                                              Units are # of
                                                              correct choices.
                            10

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                             TABLE IV

Neuropsychological Outcome Measures in High and Low Lead Children
Test
Maze Coordination
Dominant Hand
Non-Dominant
Groove Steadiness
Dominant Hand
Non- Dominant
Motor Steadiness
Dominant Hand
Non-Dominant
Grooved Pegboard

HL
LL
HL
LL
HL
LL
HL
LL
HL
LL
HL
LL
HL
LL
N
23
16
22
16
23
16
23
16
23
16
23
16
22
16
Median
Score
16.0
12.5
22.5
23.0
10.5
8.5
12.5
13.0
13.1
11.0
18.0
19.0
40.1
41.5
Ran<
29
34
28
24
30
23
32
27
29
41
24
29
28
42
                                   228.0
                                   215.0
                                   207.0
1.27
                                   174.0   -0.29
                                   150.0   -0.77
NS
                                   160.5   -0.46   NS
0.90   NS
                                   172.0   -0.34   NS
       NS
0.66   NS
       NS
                                                              Remarks
Units are time in
seconds touching side
of maze, sum of 2 trials/
hand.
     Units are time in
     seconds touching side
     of groove, sum of 2
     trials/hand.
     Units are time in
     seconds touching edge
     of holes, sum of 1 trial
     on each of 4 holes/hand.
     Units are time in
     seconds to completion.
                                  11

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Discussion

     Impaired function in children with past elevations of blood lead levels,
but no history of encephalopathy was found in two areas: eye-hand coordination
 (Frostig I), and attention as measured by reaction time under conditions of
varied delay.  Suggestive, but not statistically different, differences were
also found in Maze Coordination (another measure of eye-hand coordination)
and Tactile Form Recognition with the non-dominant hand.

     On a large number of other tests of fine and gross motor function,
language processing ability, and cognition we failed to find significant
differences.  It is possible that low level lead exposure does not affect
performance in these areas.  On the other hand, it is possible that lead
effects could have been overlooked because the sample size may have been
too small to detect subtle differences in exposure, or that the tests employed
were insensitive to small lead effects.  Because a large number of tests were
applied, and a small number of significant differences between high and low lead
subjects observed, the interpretation of the positive differences must be drawn
with caution.

     The identification of early lead exposure by blood lead determination has
certain well-recognized methodologic difficulties inherent in its use.  In this
study we were compelled to rely upon blood lead data obtained in a large public
health screening program.  In some cases only one sample per child was obtained.
The bloods were drawn at approximately 48 months of age, about one year past the
time when the incidence of pica begins to decline.  The blood lead levels may
be considered an estimate of exposure, but it is possible that some of our
controls had higher levels earlier in their lives.

     The difficulties in eye-hand coordination and attention are consistent
with the earliest report of late effects of lead exposure by Byers and Lord (1)
who reported sensorimotor defects, impulsivity and short attention span as
prominent sequelae.  Bradley and Baumgartner (19) and Mellins and Jenkins (20)
also found that children who recovered from lead intoxication had impaired
perceptual motor function when later studied.

     Children with "asymptomatic" increases in body lead burden have also been
reported to perform less adequately in these areas by Perino and Ernhart  (4)
 (perceptual items of McCarthy Scale), Burde and Choate  (5) (fine motor perfor-
mance on Binet Scale), and Landrigan et al, (8)  (performance items of Wechsler
Scale).

     The differences in attention found may bear on clinical observations
reported.  Children who recover from plumbism are frequently hyperactive  (1).
David (6) has reported that hyperactive children with no history of antecedent
risk factors have higher mean blood lead levels, and when chelated, excrete more
lead in their urine.  Silbergeld and Goldberg  (21), Michaelson and Sauerhoff  (22)
have produced hyperactivity in suckling rats given lead in mother's milk.  This
paradigm (reaction time under conditions of varying delay) has been shown to
discriminate between children with learning disabilities and controls matched on
I.P., and appears to be a sensitive method of scaling one function of attentional
performance.
                                        12

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     While the difference between the high lead and control children reached
statistical significance only in the fourth block of trials, the high lead
children performed less well in each block.  Further study of a larger sample
of subjects is indicated.
                                        13

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                             REFERENCES

 1.  Byers, R.K. and Lord, E. E.  Late effects of lead poisoning on mental
     development.  Am. J. Dis.  Child.  66:471, 1943.

 2.  Lir.-Fu, Jane S.  Undue absorption of lead among children - a new look
     at an old problem.  NEJM 286:702-710, 1972.

 3.  Medical aspects of childhood poisoning.  IJSM'7: Health Rep. 86:140-143,
     1971.

 4.  Perino, I. and Ernhart, C.  The relation of subclinical lead level to
     cognitive and perceptual performance in Black preschoolers.  J. Learn.
     Disabil. 7:616-620, 1974.

 5.  Burde, B. de la, Choate, M. S., Jr.   Does asymptomatic lead exposure in
     children have latent sequelae?  J. Pediatr. 81:1088-1091, 1972.

 6.  David, 0., Clark, J., and Voeller, K.  Lead and hyperactivity.  Lancet
     pgs.  900-903, October 28,  1972.

 7.  Pueschel, S. M., et al.  Children with an increased lead burden.  A
     screening and follow-up study.  JAMA 222:462-466, 1972.

 8.  Landrigan, P. and Whitworth,  R. et al.   Neuropsychological dysfunction
     in children with chronic low-level lead absorption.   Lancet, March 29,
     1975.

 9.  MacKeil, J.L. and Ptasnik, J. A.   Evaluation of long term effects of
     elevated blood lead concentrations in asymptomatic children.  Int.
     Synp.:Recent Advances in the Assessment of the Health Effects of
     Environmental Pollution, WHO, CEC, EPA, Paris, June 26, 1974.

10.  Lansdowne, R. G., et al.  Blood lead levels, behavior and intelligence.
     A population study.  Lancet pgs.  538-541, March 30,  1974.

11.  Kotok, D.  Development of children with elevated blood lead levels:  A
     controlled study.  J. Pediatr. 80:57, 1972.

12.  Beery, K. E. and Buktenica, N. A. Developmental Test of Visual-Motor
     Integration, Follett Educational Corp., Chicago, 1967.

13.  Frostig, Marianne, Lefever, W., Whittlesey, J. R. B. Developmental Test
     of Visual Perception, Consulting Psychologists Press, Palo Alto,
     California, 1966.

                                       14

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14.  Dunn, L. M. Peabody Picture Vocabulary Test.   American Guidance  Service,
     Inc., Circle Pines, Minnesota,  1965.

15.  Rutter, M., Graham, P.,  Yule,  W.   A Neuropsychiatric Study in Childhood.
     Philadelphia: J. B. Lippincott Co., Pg. 81,  1970.

16.  Shakow, D.  Segmental set.   Arch.  Gen. Psychiat.  6:17, 1962.

17.  Kirk, S. A., McCarthy, J.  J.,  Kirk, W. D.   Illinois Test of
     Psycholinguistic Abilities.  University of Illinois Press, Urbana,
     Illinois, 1968.

18.  Halstead, W. C.  Brain and Intelligence.  University of Chicago  Press,
     Chicago, 1947.

19.  Bradley, J. E. and Baumgartner, R. J.   Subsequent mental development of
     children with lead encephalopathy  as related to type of treatment.   J.
     Pediatr.  53:311, 1958.

20.  Mellins, R. B. and Jenkins, C.  D.  Epidemiological and psychological
     study of lead poisoning in children.   JAMA 158:15, 1955.

21.  Silbergeld, Ellen K., Goldberg, A. M.   Hyperactivity:  A lead-induced
     behavior disorder.  Env. Hlth.  Persp.  #7,  May 1974.

22.  Michaelson, I. A. and Sauerhoff, M. W.  Animal models of human disease:
     severe and mild, lead encephalopathy in the neonatal rat.  Environmental
     Health Perspectives #7,  May 1974,  pp.  201-226.
                                     15

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                                Appendix I

                           Parent Questionnaire
Child's Name
Birthdate
             Mother's Name
                Last
First
Last
First
          Month Day Year

Grade 	

Child's Birthplace 	
       Race (specify):  Caucasian
                        Black 	
                        Other 	
                                (Specify)
Length of Pregnancy:  Early	  9 mos._

                      How early

Birthweight 	Ibs. 	pz.
Complications:  Yes
                No
 Specify:
Child left hospital with
mother:     Yes ______
            No	    If no, why:
                    Late	
                        ——••^•••i^H

                    How late
Illness:
  Head Injury:  Yes	No	

  Hospitalizations: Yes	 No_

    If yes, explain:	

  Seizures:  Yes 	No

Immunizations:

  Smallpox:  Yes      No	
  Diptheria: Yes	No	
  Polio:     Yes	No
        Oral	
        Shots	
  Measles:   Yes      No
        Other problems (explain):
        Has your child ever experienced:

          Pica (eating of non-food substances)
          Abdominal Colic
          Clumsiness	
          Irritability	
                                   16

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Parent's Picture of Child

  Is he/she active: No	Yes	Overactive	

  Is his/her general health good: No	 Yes	

School Adjustment:

  Has teacher called you in other than for routine talks? No	 Yes	
  Any failed grades? No	Yes
  Special problems?  No	Yes
  Are your child's marks generally:    Poor
                                       Good	
                                       Very good

General Adjustment                          No      Yes

  Is your child generally happy?           	    _____

  Does he or she fight excessively?        	    	

  Can your child stick to one task?        	    	

  Sit quietly when asked?                  	    	

  Ignore distractions?                     	    	

  Does your child get along with friends?  _____    ______

  Is he/she a loner?                       	    	


Parent Data

  Mother's age at date of child's birth: 	years

  Marital status:  Married _____  Separated 	Divorced	Widowed 	

                   Never married 	

  Father's occupation	Education 0 1-6 7 8 9 10 11 12
                                                          college	
  Mother's occupation 	                 Education 0 1-6 7 8 9 10 11 12
                                                          college 	
                                     17

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                                APPENDIX  II
(First Contact Letter)
                   The  Children's  Hospital  Medical  Center
                   300 Longwood Avenue, Boston, Massachusetts 02115, Telephone: (617): 734-6000
Dear Mrs.
     We are  conducting a study of child development in relation to exposure to
lead.  The children we are studying were tested for lead when they were  five years

old or younger, and are now between six and eight years of age.  Your child
              is eligible for the study.

     The children in the study will receive tests of motor coordination, sensory

ability, and problem solving.  There will be np_ blood tests.   Many children have
found the tests an interesting and pleasant challenge.  There -will be only one
testing session which will occupy about 2 1/2 to 3 hours.  As a stipend, each

family will  receive $10.00 plus transportation expenses.
     This is an important study in which you can make a contribution  to  the
understanding  of what helps children to develop fully.  We hope you will choose

to participate by fillino out the enclosed card.  We will then make an appointment
at your convenience.
     If you  have any questions, please do not hesitate to contact us  at  734-6000,
extension 3400.
                                      Sincerely,


                                      Herbert L. Needleman, M.D.


Enclosure
                                       18

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                                   TECHNICAL REPORT DATA
                           (Please read Instructions on the reverse before completing)
1. REPORT NO.
 EPA-600/1-77-037
                                                           3. RECIPIENT'S ACCESSION NO.
4. TITLE AND SUBTITLE
 Studies in Subclinical  Lead  Exposure
               5. REPORT DATE
                 June 1977
                                                           6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)

 Herbert L. Needleman,  M.D.
                                                           8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS

 The Children's Hospital  Medical  Center
 300 Longwood Ave.
 Boston, MA 02115
                10. PROGRAM ELEMENT NO.

                   1AA601
                11. CONTRACT/GRANT NO.

                 68-02-1239
12. SPONSORING AGENCY NAME AND ADDRESS
 Health Effects Research  Laboratory
 Office of Research  and Development
 U.S. Environmental  Protection Agency
 Research Triangle Park.  N.C.  27711
                                                           13. TYPE OF REPORT AND PERIOD COVERED
RTP,NC
                14. SPONSORING AGENCY CODE
                   EPA 600/11
15. SUPPLEMENTARY NOTES
16. ABSTRACT
      This study was  initiated to examine the utility of neuropsychologic testing  in
 identifying deficits in children with asymptomatic  elevations in blood lead  levels.
      From the  files  of the Boston Lead Screening  Project we selected black male
 children between  the acres of six and eight years  of age, considered symptomatic  for
 lead toxiclty  who had blood lead tests recorded  between the ages of 1-1/2 and 5 years
 of age.  High  lead subjects were children with  one  or more blood lead levels greater
 than 50ug/dl.   Low lead subjects were children  with no blood lead level greater  than
 30ug/dl.   Subjects  were tested by a battery of neuropsychologic tests measuring
 intelligence,  verbal performance, visual motor  performance, gross and fine motor
 function, and  attention span.  Other covariates measured were socioeconomic  status,
 birthweight, and  medical history.   High lead children were consistently slower  at'
 each block of  trials on the Reaction Time under Varying Conditions of Delay  (a measure
 of attention),  and performed significantly less well on Subtest I of the Frostig
 Battery.  High  lead  subjects tended to perform  less well on the Maze Coordination
 Test, and on the  Tactile Form Recognition Test  with the non-dominant hand
17.
                               KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
                                              b.lDENTIFIERS/OPEN ENDED TERMS
                             c. COSATI Field/Group
 lead
 toxicity
 biological surveys
 demographic surveys
 sociopsycho'logical surveys
 children
                               06 T
13. DISTRIBUTION STATEMENT

   RELEASE TO PUBLIC
   19. SECURITY CLASS (ThisReport/
    UNCLASSIFIED
21. NO. OF PAGES

  25
                                              20. SECURITY CLASS {Thispage)

                                               UNCLASSIFIED	
                                                                        22. PRICE
EPA Form 2220-1 (9-73)
                                            19

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