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#758 - From Silent Spring to Scientific Revolution -- Part 2, 11-Dec-2002

by John Peterson Myers*

[Continued from RACHEL'S #757. We are exploring the shifts in
scientific thinking about chemicals and health that have occurred
since the publication of Rachel Carson's SILENT SPRING in 1962 --
shifts resulting from the discovery that some industrial
chemicals in the environment can interfere with hormones and
growth factors in plants and animals, including humans. This
essay first appeared in SAN FRANCISCO MEDICINE, November 2002.
See http://www.sfms.org/sfm/. For more documents related to these
topics, see http://www.OurStolenFuture.org and
http://www.ProtectingOurHealth.org. --Peter Montague, editor]

Low Doses May Be More Potent than High Doses

Another key shift [in scientific thinking] is the acknowledgement
that the assumption that the dose makes the poison can be
misleadingly simplistic, if it is used to imply that only high
dose exposures induce effects. In fact, low exposure levels
sometimes cause effects not seen at higher levels [for example,
see 12,13,14]. Researchers are now intensely pursuing these
non-monotonic dose response curves and the uncertainty about
their underlying mechanisms, which likely vary from case to case.
[A "non-monotonic dose response curve" means that as the dose of
a chemical is raised or lowered, the effect does not necessarily
rise or fall in lock step with the dose. In some cases, low doses
may cause greater effects than high doses.] One plausible
hypothesis [to explain why dose and response do not always move
together in lock step] is that at low, physiological levels, the
contaminant interferes with developmental signaling but does not
activate biochemical defenses against impacts that would be
caused by higher exposures. At somewhat higher levels, these
defenses are activated and the contaminant is successfully
detoxified. At even higher levels, the defense mechanisms are
overwhelmed by the toxicant and more traditional toxicological
effects are induced.

Common Chemicals Can Disrupt Hormone Signals

As scientific research has focused on mechanisms of message
disruption, it has implicated a wide array of chemicals. This
expansion has involved both ongoing identification of compounds
capable of interfering with estrogen, which was the initial
focus, as well as research broadening the range of message
systems studied. Some of the most troubling discoveries about new
actors is that they involve compounds in widespread use in
consumer products, including plastic additives like phthalates
and plastic monomers like bisphenol A, which leaches from
polycarbonate products [for example, see 15,16]. [Polycarbonates
are strong plastics, such as Lexan, used in drink bottles,
eyeglass lenses and shatterproof windows.]

New Studies Reveal Unsuspected Health Effects

That is not to say that we have complete understanding of even
the best known contaminants. This reality was highlighted by a
study published in 2001 about DDT, in which Longnecker and
others[17] report a highly significant association between DDT in
maternal serum [blood] and the likelihood of preterm [premature]
birth. Their study used birth records and stored serum from the
mid 1950s-60s. They concluded that the U.S. had experienced a
hitherto undetected epidemic of preterm birth during this period
because of DDT use. Longnecker (personal communication) went
further to estimate that because of the close association between
preterm birth and infant mortality, up to 15% of infant mortality
during that period may have been attributable to DDT use.

Chemicals Interfere with Hormones in Unsuspected Ways

Disrupting chemicals have been identified that interfere with
[many hormone systems, such as] estrogen, androgen, progesterone,
thyroid, insulin and glucocorticoid signaling, among others. The
mechanism does not always involve mimicking (or inhibiting)
ligand-receptor binding. [Many hormones work like a key fitting
into a lock and the scientific name for this is ligand-receptor
binding.] For example, as noted above, atrazine appears to
enhance aromatase conversion of testosterone to estrogen.

Chemicals Can Disrupt Hormones in Several Ways

Signal disruption may also intercede in steps leading to gene
activation after ligand-receptor binding. [In other words, after
the hormone key fits into one of the cell's locks, other things
should happen, but some chemicals disrupt normal events at this
stage.] This was established by in vitro [test tube] experiments
showing that arsenic selectively inhibits gene activation by the
glucocorticoid-receptor complex after normal ligand-receptor
binding and subsequent entry into the cell nucleus, at arsenic
concentrations far beneath cytotoxic [toxic to cells] levels.[18]
While human health impacts have yet to be demonstrated via this
mechanism, dysfunctions [interferences] in glucocorticoid action
have been linked to weight gain/loss, protein wasting,
immunosuppression, insulin resistance, osteoporosis, growth
retardation, and hypertension.

Mixtures are Important but Not Often Studied

Another important issue raised by emerging science is the
powerful interactions that can occur within mixtures of
chemicals, even though regulatory toxicology is conducted
virtually exclusively on pure single compounds. Two results
published in 2002 emphasize the importance of considering
mixtures: In the first, Rajapakse and others[19] demonstrated
that a mixture of estrogenic compounds, each present at a level
beneath that capable of producing a statistically detectable
estrogenic response in an in vitro [test tube] system, combined
to more than double the response of the system to 17-estradiol
[the commonest form of female sex hormone]. In the second,
Cavieres and others[14] found that a common off-the-shelf
dandelion herbicide mixture strongly reduced fetal implantation
[successful pregnancy] rates in mice at one-seventh the
concentration considered safe for its principal herbicidal
component, 2,4-D, by the U.S. Environmental Protection Agency.

Chemicals and Germs Together Increase Disease Risks

The issue of mixtures is complicated further by interactions now
known to occur between contaminants and infectious agents
[bacteria and viruses]. Large increases in disease risk can be
associated with simultaneous exposure to contaminants and
infectious agents. For example, Rothman and others[20] reported a
greater than 20-fold increase in relative risk to non-Hodgkins
Lymphoma with combined exposure to elevated (but still
background) PCBs and Epstein-Barr virus. The mechanism underlying
this result is unknown, but is possibly due to well-established
immune system impairment by PCBs. If this mechanism is
widespread, then current estimates of morbidity and mortality due
to contamination are likely to be unrealistically low. Immune
system interference by a variety of contaminants is widely
reported (for example, Baccarelli[21]).

Traditional Regulatory Science May Not Protect Us

Together these conceptual shifts are also challenging the
adequacy of current epidemiology to guide regulatory standards.
The patterns underlying these conceptual shifts -- including (1)
non-monotonic dose response curves; (2) windows of vulnerability
during development; (3) the ubiquity of mixtures; (4) the
likelihood that multiple chemicals can induce similar impacts via
disruption of developmental processes; (5) the same chemical can
cause different impacts depending upon when exposure occurs; (6)
long latencies [delays] between exposure and manifestation of
impact in a mobile population, etc. -- all increase the
likelihood of false negatives [falsely concluding that no harm is
occurring] in epidemiology as it is currently practiced.

Thus the revolution in science that Rachel Carson stimulated
raises today a series of troubling questions about whether
current health standards truly protect public health. Effects of
low level, background exposures are likely to be far more
widespread than acknowledged, and involve many more health
endpoints [health effects] than traditionally considered, yet
these new mechanisms of toxicity thwart the epidemiological tools
now available to establish human harm.

Important Role for Health Professionals

We are confronting an enormous gap between what science now tells
us about the links between contamination and health, and the
antiquated approaches still used to safeguard public health.
Health professionals will be important contributors to narrowing
that gap, first by informing themselves about the underlying
science, and then by helping to advance public understanding of
the emerging evidence. Carson's scientific revolution can drive a
transformation in public health that reinvigorates investments in
prevention through exposure reduction.

===========

* John Peterson Myers, Ph.D., is co-author of OUR STOLEN FUTURE
(paperback: Plume, 1997; ISBN 0452274141), Senior Advisor to the
United Nations Foundation and Senior Fellow, Commonweal, Bolinas,
California. See http://www.OurStolenFuture.org and
http://www.ProtectingOurHealth.org.

[12] vom Saal, F, BG Timms, MM Montano, P Palanza, KA Thayer, SC
Nagel, MD Dhar, VK Ganjam, S Parmigiani and WV Welshons. 1997.
Prostate enlargement in mice due to fetal exposure to low doses
of estradiol or diethylstilbestrol and opposite effects at high
doses. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES USA 94:
pgs. 2056-61.

[13] National Toxicology Program. 2001. Report of the Endocrine
Disruptors Low-dose Peer Review. http://ntpserver.niehs.-
nih.gov/htdocs/liason/LowDosePeerFinalRpt.pdf (omit the
hyphen).

[14] Cavieres, MF, J Jaeger and W Porter. 2002. Developmental
Toxicity of a Commercial Herbicide Mixture in Mice: I. Effects on
Embryo Implantation and Litter Size. ENVIRONMENTAL HEALTH PER-
SPECTIVES 110: pgs. 1081-1085

[15] Gray, LE, J Ostby, J Furr, M Price, DNR Veeramachaneni and L
Parks. 2000. Perinatal Exposure to the Phthalates DEHP, BBP, and
DINP, but Not DEP, DMP, or DOTP, Alters Sexual Differentiation of
the Male Rat. TOXICOLOGICAL SCIENCES 58: pgs. 350-365

[16] Masuno, H, T Kidani, K Sekiya, K Sakayama, T Shiosaka, H
Yamamoto and K Honda. 2002. Bisphenol A in combination with
insulin can accelerate the conversion of 3T3-L1 fibroblasts to
adipocytes. JOURNAL OF LIPID RESEARCH 3: pgs. 676-684.

[17] Longnecker, MP, MA Klebanoff, H Zhou, JW Brock. 2001.
Association between maternal serum concentration of the DDT
metabolite DDE and preterm and small-for-gestational-age babies
at birth. THE LANCET 358: pgs. 110-114.

[18] Kaltreider, RC, AM. Davis, JP Lariviere, and JW Hamilton
2001. Arsenic Alters the Function of the Glucocorticoid Receptor
as a Transcription Factor. ENVIRONMENTAL HEALTH PERSPECTIVES 109:
pgs. 245-251.

[19] Rajapakse, N, E Silva and A Kortenkamp. 2002. Combining
Xenoestrogens at Levels below Individual No-Observed-Effect
Concentrations Dramatically Enhances Steroid Hormone Action.
ENVIRONMENTAL HEALTH PERSPECTIVES 110: pgs. 917-921.

[20] Rothman, N., K. P. Cantor, A Blair, D Bush, JW Brock, K
Helzlsouer, SH Zahm, LL Needham, GR Pearson, RN Hoover, GW
Comstock, PT Strickland. 1997. A nested case-control study of
non-Hodgkin lymphoma and serum organochlorine residues. THE
LANCET 350 (July 26): pgs. 240-244.

[21] Baccarelli, A, P Mocarelli, DG Patterson Jr., M Bonzini, AC
Pesatori, N Caporaso and MT Landi1. 2002. Immunologic Effects of
Dioxin: New Results from Seveso and Comparison with Other
Studies. ENVIRONMENTAL HEALTH PERSPECTIVES 110: pgs. 1169-1173.