> Dioxins, a persistent organic pollutant ...
A critical comparison of murine pathology and epidemiological data
of ...dioxin and dioxin-like compounds (DLCs) induce numerous
toxicities, including developmental, endocrine, immunological, and
multi-organ carcinogenic, in animals and/or humans ... humans are
exposed daily to a combination of DLCs, primarily via ingestion of
food ... clear consistency in the target organs affected (liver, oral
cavity, cardiovascular system, immune system, thyroid, pancreas, and
lung) could be seen in both human studies and rodent toxicity and
carcinogenicity investigations. PMID: 18098033
Dioxin: a review of its environmental effects and its aryl hydrocarbon
receptor biology.
A highly persistent trace environmental contaminant and one of the
most potent toxicants known is TCDD. TCDD induces a broad spectrum of
biological responses, including induction of cytochrome P-450 1A1
(CYP1A1), disruption of normal hormone signaling pathways,
reproductive and developmental defects, immunotoxicity, liver damage,
wasting syndrome, and cancer. Its classification was upgraded from
"possible human carcinogen" (group 2B) to "human carcinogen" (group 1)
by the International Agency for Research on Cancer (IARC) in 1997.
Exposure to TCDD may also cause changes in *** ratio, and tumor
promotion in other animals. Because of the growing public and
scientific concern, toxicological studies have been initiated to
analyze the short- and long-term effects of dioxin. TCDD brings about
a wide variety of toxic and biochemical effects via aryl hydrocarbon
receptor (AhR)-mediated signaling pathways ... PMID: 15900503
On the significance of the role of cellular stress response reactions
in the toxic actions of dioxin.
Dioxin is known to cause many toxic effects that vary greatly in
different tissues, ages, genders, and species. In this review, an
attempt has been made to sort out major signaling pathways involved in
the expression of the toxicities of dioxin. The major strategy adopted
in analyzing its major signaling pathways is to view the toxic actions
of dioxin as the result of the Ah receptor-mediated expression of a
major cellular emergency stress response signal. Evidence pointing to
the similarities between the symptoms of poisoning by dioxin and those
produced by chronic administration of typical stressors, particularly
lipopolysaccharides (LPS), bacterial endotoxins, has been assembled
and analyzed. The common symptoms are wasting syndrome,
atherosclerosis, fatty liver, and thymic atrophy. On the other hand,
oxidative stress caused by cytochrome P450 induction is one of the
typical stresses of dioxin poisoning, but not LPS poisoning ...These
observations as well as additional experimental data sup****t the idea
that one of the major functions of the Ah receptor could be the
elicitation of cellular stress response reactions. Another key point
in understanding the toxic action of dioxin is that, unlike other
cases of stressors, dioxin signaling becomes chronically sustained
because of its extreme persistence in the human body, its half-life of
7-10 years, and its selective ac***ulation in fatty target tissues.
PMID: 12906918
Human health effects after exposure to TCDD.
In 1949, the first descriptions of human exposure to TCDD-contaminated
chemicals were re****ted after a trichlorophenol reactor explosion in
Nitro, West Virginia, USA. Re****ted non-cancer health effects included
a range of conditions affecting most systems. Additional re****ts of
the health consequences of exposure continued through the remainder of
the century. The majority of effects have been re****ted among highly
exposed groups including occupational populations, such as chemical
production workers, pesticide applicators, and individuals who handled
or were exposed to materials treated with TCDD-contaminated
pesticides, and among residents of communities contaminated with
tainted waste oil (Missouri, USA) and industrial effluent (Seveso,
Italy). For only six exposed populations were biological measurements
of TCDD-contaminated collected and used to examine the relation****p
between non-cancer health effects and exposure. Of the many non-cancer
health effects thought to be associated with TCDD exposure, only
chloracne, elevations in GGT and triglyceride levels, and alterations
in FSH and LH were related to serum TCDD levels. Mortality from
cardiovascular diseases also appeared to be elevated among cohorts of
exposed chemical workers and Seveso residents. Continued surveillance
of the health of exposed populations will be useful in identifying the
long-term effects of both high and low TCDD exposure. PMID: 10912244
Non-carcinogenic effects of TCDD in animals.
Exposure to TCDD and related chemicals leads to a plethora of effects
in multiple species, tissues, and stages of development. Responses
range from relatively simple biochemical alterations through overtly
toxic responses, including lethality. The spectrum of effects shows
some species variability, but many effects are seen in multiple
wildlife, domestic, and laboratory species, ranging from fish through
birds and mammals. The same responses can be generated regardless of
the route of exposure, although the administered dose may vary. The
body burden appears to be the most appropriate dosimetric. Many of the
effects often attributed to TCDD are associated with relatively high
doses: lethality, wasting, lymphoid and gonadal atrophy, chloracne,
hepatotoxicity, adult neurotoxicity, and cardiotoxicity. Changes in
multiple endocrine and growth factor systems have been re****ted in a
manner which is tissue, ***, and age-dependent. The most sensitive
adverse effects observed in multiple species appear to be
developmental, including effects on the developing immune, nervous,
and reproductive systems. Such effects have been observed at maternal
body burdens in the range of 30-80 ng/kg in both non-human primates
and rodents. Biochemical effects on cytokine expression and
metabolizing enzymes occur at body burdens which are within a factor
of ten of the clearly adverse developmental responses. Thus, effects
on the immune system, learning, and the developing reproductive system
of multiple animals occur at body burdens which are close to those
present in the background human population. PMID: 10912242
Ah receptor ligands and tumor promotion: survival of neoplastic cells.
A number of agonists of the aryl hydrocarbon or dioxin receptor (AhR)
are potent tumor promoters in rodent liver. The prototype compound is
TCDD. Tumor promotion by TCDD is likely to be AhR-mediated. Tumor
promoters may affect the rate of division, terminal differentiation or
death (apoptosis) of tumor precursor cells ... PMID: 10720714
Risk *****sment of dioxins and the effect as the endocrine disrupters
In 1990, WHO recommended the TDI (Tolerable Daily Intake) of 10 pg/kg
bw/day for dioxin. Since then, industrialized countries have set TDIs
or exposure limits based on their own evaluation of the exposure
levels and the toxicity of dioxin. In Japan, the MHW announced 10 pico
grams TCDD/kg bw/day as the tem****ary TDI in 1996. WHO reevaluated the
TDI in May 1998 and announced the TDI in the range of 1-4 pg TEQ/kg bw/
day including coplanar PCBs, which will definitely have a big impact
all over the world. Moreover, dioxins, as endocrine disrupting
chemicals, are reviewed on their hazards on health and the mechanism
of actions. PMID: 10097509
Note: a pico is 1/1,000,000,000,000 th
It is very likely that the average intake of dioxins is above TDI.
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