NCD980602163_19951115_Warren County PCB Landfill_SERB C_Synopsis of 13th Annual Int'l Neurotoxicity Conference Reports of PCB Effects in Animals and Humans-OCR

North Carolina Department of Environment, Health, and
Natural. Resources
William L. Meyer, Director
Solid Waste Management Division
Please:
_ Draft a reply for my signature
_ Take appropriate action
_ Approve
Dale: 1 / br/15
_ For your infom1ation
_ See me about attached
_ Handle and report to me
_ Note and return attached material to me
Remarks:
State of North Carolina
Department of Environment,
Health and Natural Resources
Division of Epidemiology
James B. Hunt, Jr., Governor
Jonathan B. Howes, Secretary
Michael Moser, M.D., M.P.H.
MEMORANDUM
November 15, 1995
TO: William Meyer, Director
Division of Solid Waste Management
FROM: Kenneth Rudo, Ph.D.,Toxicologist {JJ1rl
AVA
DEHNR
Medical Evaluation and Risk Assessment Branch
Occupational and Environmental Epidemiology Section
SUBJECT: Synopsis of 13th Annual International Neurotoxicity Conference Reports of
PCB Effects in Animals and Humans
The major focus of the above conference was to present studies that illustrated the potential of
many man-made chemicals to disrupt the endocrine system of animals and humans. These
chemicals seem to be toxic during the embryonic, fetal and early postnatal periods . These
compounds either mimic or interfere with hormones, growth factors , inhibiting substances ,
and neurotransmitters that control the development of the nervous system, the immune system,
and the endocrine system. Because these changes are in most cases irreversible and appear as
subtle and nonsubtle functional defects rather than physical defects, documenting these effects
in humans and animals may be difficult. Another issue that was debated was the question
"Are human exposures to endocrine disrupters (including dioxins and PCBs) derived from
industrial chemicals and their metabolic products responsible, at levels found in the
environment, for many of the reproductive, developmental, and neurotoxic effects reported for
animals and humans at higher concentrations?" There was a spirited discussion of this
question. In addition, several studies were presented later in the conference that would seem
to suggest that subtle toxic effects are evident.
A significant portion of the meeting was devoted to a discussion of recent studies on the
neurotoxic and neurodevelopmental effects of dioxins and PCBs in animals and humans.
Mechanistic studies indicated that dioxins and certain PCBs act by binding to a transcription
factor called the Ah receptor. This receptor is activated to a form that binds to a specific
regulatory region on responsive genes, thereby modulating transcription rates. This incorrect
gene expression may effect growth factors and cellular states of differentiation which can lead
to a toxic endpoint. The studies presented in animals and humans pointed out behavioral and
P.O. Box 27687, Raleigh, North Carolina 27611-7687
An Equal Opportunity Affirmative Action Employer 50% recycled/ 10% post-consumer paper
William Meyer
November 15, 1995
Page Two
biochemical changes which clearly illustrate an extreme sensitivity of developing
neuroendocrine pathways to certain PCBs and dioxins. In all the studies, it was important to
identify the specific PCB congeners responsible for these effects, as their toxic effects are
dependent on the individual PCB congener.
Several studies in humans specifically related to PCB neurodevelopmental toxicity were
presented. These studies primarily involve follow-up cohorts of young children. The 117
children born between 1979 and 1985 to women poisoned in Taiwan, the Yu-cheng children,
are the best documented high-dose cohort. These children are still followed by Yue-Liang
Guo and Mei-Lin Yu et al in Taiwan, ROC. This study found reduced neurocognitive
function, disordered behavior, slightly stunted overall growth and penile growth and delayed
sexual development. There are at least three cohorts of children without special exposures
who have been followed from birth--two in the US, begun in the 1970s, and one in the
Netherlands, begun in the 1990s. In Michigan, Sandra and Joseph Jacobson et al follow about
230 children. The Michigan cohort over-represents offspring of women who ate large
quantities of Lake Michigan fish possibly contaminated with PCBs. This study found deficits
in memory, attention function, and physical growth in infancy and early childhood. In North
Carolina, Beth Gladen and Walter Rogan et al follow about 750 children. This cohort was
drawn from the general population and found depressed neonatal behavior and poor infant
motor function. These children are now peri-pubertal. In the Netherlands, Corinne Koopman-
Esseboom et al are evaluating about 400 children with better analytical chemistry and more
intensive neurological tests than were possible in the late 1970s. Children at 18 months of age
had reduced neonatal neurological optimality scores. However, no clinical neurological
abnormalities were observed. Slight changes in thyroid hormone levels were also observed.
Other planned or possible cohorts include children in the Arctic Inuit, St. Lawrence River area
Mohawks, Vietnamese, residents near Seveso, and Canadian or US anglers. A researcher
named George Lambert has developed a simple, non-invasive method of measuring enzyme
induction in children and adults, and has used the method in children from several of these
groups who have had unusual exposures to PCBs or similar compounds.
I believe these were relevant studies relating to concerns from the PCB landfill working group.
At your request, I will prepare a presentation to the working group. Although the talk may be
somewhat technical in nature, I believe we can couple the results of these studies with a
discussion of their relevance to the exposure scenarios presented by the Warren County PCB
landfill. Please let me know if you wish to go forward with the presentation.
If you have any further questions, please feel free to contact me at 733-3410 or 715-6430.
KR/rm