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#391 - Dioxin Reassessed -- Part 2, 25-May-1994

After three years of study, U.S. Environmental Protection Agency [EPA]
is about to publish a 9-volume draft "scientific reassessment" of
dioxin and other dioxin-like chemicals, including dibenzofurans and
some PCBs [polychlorinated biphenyls]. PCBs are industrial poisons now
banned in the U.S. because of widespread environmental damage. Dioxins
and furans are highly toxic byproducts of certain industrial operations
including incineration, tire burning, combustion of coal and oil,
manufacture of paper and some pesticides, metal smelting, and perhaps
diesel engine exhausts [pgs. 6-9]. There are probably other sources as
well. Dioxins and furans are created when chlorine combines with other
chemicals at high temperatures.

A copy of EPA's summary volume (Chapter 9) was leaked to the press in
mid-May. We obtained a copy and reported some of its findings and
conclusions last week, focusing on the cancer hazard. This week, we
bring you more, stressing non-cancer effects. [Page numbers inside
square brackets refer to EPA's draft of Chapter 9, dated May 2, 1994.]

According to EPA, nature produces only small amounts of dioxin. The
vast majority of dioxin is created by human economic activities. Since
about 1920, industrial emissions, and inattention to the potent toxic
effects of dioxin-like chemicals, have allowed the environment to
become widely contaminated with significant quantities of dioxins,
furans and PCBs. As a result, all Americans eat and breathe small but
important amounts of dioxin every day.

Human exposure to dioxin begins early in life. A human fetus lives in
the womb enclosed inside a fluid-filled sac called the placenta, which
provides a barrier to many poisons that the mother might ingest. Unlike
many other poisons, dioxin crosses the placenta and begins affecting
the fetus [pg. 23]. The human body retains dioxin, so a "body burden"
begins accumulating in each of us during our early months in the womb.
[1]

In humans and other species, it is the growing embryo or fetus that is
most sensitive to the toxic effects of dioxin-like chemicals. EPA: "A
general finding in fish, bird, and mammalian species is that the embryo
or fetus is more sensitive to TCDD-induced mortality than the adult.
[TCDD is a shorthand name for dioxin.] Thus the timing of TCDD exposure
during the life history of an animal can greatly influence its
susceptibility to overt dioxin toxicity." [pg. 36]

Growth occurs in two ways: cells multiply, and cells of one type turn
into cells of another type (a process called differentiation). Thus
some cells become eyes and other cells become fingers by
differentiation. Dioxin-like chemicals can disrupt both cell
multiplication and cell differentiation.

"Of particular interest to the risk assessment process is the fact that
a wide variety of developmental events, crossing three vertebrate
classes and several species within each class, can be perturbed,
suggesting that dioxin has the potential to disrupt a large number of
critical developmental events at specific developmental stages. Not
only can these changes lead to increases in embryo/fetal mortality, but
they can disrupt organ system structure and irreversibly impair organ
function." [pgs. 34-35]. In other words, damage that occurs in the womb
can last a lifetime.

After a baby (or animal) is born, rapid growth continues, so
sensitivity to the toxic effects of dioxin continues as well. Human
infants who breast feed get a particularly high dose of dioxins. EPA's
report calculates that an infant who breast feeds for a year will
receive 4% to 12% of his or her full lifetime dose of dioxin during
that one year [pgs. 15, 21]. (Despite the presence of dioxin-like
chemicals in human milk, breast feeding is still the best way to
nourish an infant; all of the alternatives are worse.[2])

Although dioxin can presumably interfere with every bodily system in
the growing infant, there is evidence that the developing immune system
is one of the most sensitive to disruption by low- level exposure to
dioxin-like chemicals. EPA says, "Furthermore, since TCDD [dioxin]
alters the normal differentiation of immune system cells, the human
embryo may be very susceptible to long-term impairment of immune
function from in utero [in the womb] effects of TCDD on developing
immune tissue." [pg. 39]

EPA points out that, "Impairment of the immune system can be considered
an adverse outcome in its own right, being responsible for induced
pathologies." [pg. 51] And: "Concern over the potential toxic effects
of chemicals on the immune system arises from the critical role that
the immune system plays in maintaining health. It is well recognized
that suppressed immunological function can result in increased
incidence and severity of infectious diseases as well as some types of
cancer. Conversely, the inappropriate enhancement of immune function or
the generation of misdirected immune responses can precipitate or
exacerbate the development of allergic and autoimmune diseases." [pg.
37] In other words, there are two ways your immune system can
malfunction: it can be depressed and fail to protect you against
bacteria, parasites, viruses and cancer. Or it can become too active
and start to attack you; this creates autoimmune diseases like asthma,
diabetes, and lupus.

EPA clearly considers these immune system hazards important; the report
spends considerable time discussing them: "Animal host resistance
models that mimic human disease are available and have been used to
assess the effect of TCDD on altered host resistance [to disease].
Results from host resistance studies provide evidence that exposure to
TCDD results in increased susceptibility to bacterial, viral,
parasitic, and neoplastic [cancer] disease. These effects are observed
at relatively low doses and likely result from TCDD-induced suppression
of immunological function." [pg. 38]

The immune system is as complex as the brain and central nervous
system.[3] Scientists speak of two basic parts of the immune system:
those that work via cells (called "cell-mediated") and those that work
in the blood stream without entering cells (called "humoral").

EPA: "Both cell-mediated and humoral immune responses are suppressed
following TCDD exposure, suggesting that there are multiple cellular
targets within the immune system that are altered by TCDD. Evidence
also suggests that the immune system is indirectly targeted by TCDD-
induced changes in nonlymphoid tissues." [pg. 38]

EPA goes on: "One potentially important indirect mechanism is via
effects on the endocrine system. Several endocrine hormones have been
shown to regulate immune responses, including glucocorticoids, sex
steroids, thyroxine, growth hormone, and prolactin. Importantly, TCDD
and other related compounds have been shown to alter the activity of
all of these hormones." [pg. 38]

The EPA's draft report speaks of "a window of sensitivity of biological
processes." [pg. 48] In other words, there are certain times during the
life of an animal (or human) when it is more sensitive to dioxin's
effects than at other times. The perinatal period (shortly before or
shortly after birth) is one such "window of sensitivity." But there are
evidently other such "windows." EPA suggests that any time the immune
system begins to respond to a challenge, disruption by dioxin can have
far-reaching effects: "It is important to consider, however, that if an
acute exposure to TCDD even temporarily raises the TCDD body burden at
the time when an immune response is initiated, there may be a risk of
adverse impacts even though the total body burden may indicate a
relatively low average TCDD level." [pgs. 38-39] Thus even a short-term
exposure to dioxin at the wrong time might cause disease in a person by
suppressing the immune system, even though the person's average
lifetime body burden of dioxin may not be greatly increased.

Dioxin may also cause inheritable genetic changes: "While dioxin and
related compounds are not generally considered to be 'genotoxic' in
traditional terms, both empirical data and the results of modeling
efforts suggest that they may be functioning indirectly to produce
irreversible genetic changes in exposed cells." [pg. 33] EPA's draft
report emphasizes that most people get their daily dose of dioxin from
their food (about 90% from meat, fish and dairy products) [pg. 12].
However, people who live near sources of dioxin emissions (listed in
our first paragraph, above), should consider that inhalation may be an
important hazard for them. EPA says, "The use of incineration as a
means of solid and hazardous waste management results in the emission
of contaminated particles that may contain TCDD and related compounds
into the environment. Thus, exposure to TCDD and related compounds may
result from inhalation of contaminated fly ash, dust and soil. Systemic
effects occur in animals after pulmonary exposure to TCDD, suggesting
that transpulmonary [lung] absorption of 2,3,7,8-TCDD does occur.
Further results suggest that the transpulmonary absorption of 2,3,7,8-
TCDD and 2,3,7,8-TBDD was similar to that observed following oral
exposure.... these data provide support for the inference that
efficient absorption will occur when particles containing dioxin and
related compounds are inhaled by humans." [pgs. 17-18]

How much dioxin is "safe"? EPA: "The USEPA has frequently defined a
reference dose (RfD) for toxic chemicals to represent a scientific
estimate of the dose below which no appreciable risk of non-cancer
effects is likely to occur following chronic exposures. In the case of
dioxin and related compounds, calculation of an RfD based on human and
animal data and including standard uncertainty factors to account for
species differences and sensitive subpopulations would result in a
reference intake levels on the order of 10-100 times below the current
estimates of daily intake in the general population." [pg. 51]

How much dioxin is "safe"? EPA's answers: For cancer hazards? Three
hundred to 600 times less than we all now take in every day. (See RHWN
#390.) For non-cancer hazards? Ten to 100 times less than we all now
take in every day.

EPA's "dioxin reasessment" raises one key public policy question: How
much additional dioxin is acceptable in the environment? To us, the
answer seems clear: zero. To protect public health, no new sources can
be allowed, and present sources must be sharply reduced.

--Peter Montague

=====

[1] The "half-life" of dioxins in humans is somewhere between 5.8 years
and 7 years [pgs. 13, 20]. (The half-life is the time it takes for half
of today's dioxin intake to be excreted.) Therefore, dioxin builds up
in our bodies as we age.

[2] See, for example, Natalie Angier, "Mother's Milk Found to Be Potent
Cocktail of Hormones," N.Y. TIMES May 24, 1994, pgs. C1, C10.

[3] Lydia Woods Schindler, UNDERSTANDING THE IMMUNE SYSTEM [NIH
Publication No. 88-529] (Bethesda, Md.: National Institutes of Health,
July, 1988).

Descriptor terms: epa; dioxin reassessment; studies; pcdfs; pcbs; tire
burning; coal; oil; fossil fuels; paper; pesticides; smelting; diesel;
chlorine; infants; fetuses; immune system; immunotoxicity; asthma;
lupus; diabetes; incineration; msw; hazardous waste; inhalation; air
pollution;