Excerpts from dioxin article

[slester@essential.org]

Very useful excerpts from a PEER-REVIEWED article that appeared in the 
September 1995 issue of Environmental Health Perspectives are presented 
below.  These findings fully support the conclusions USEPA presented in 
their September 1994 draft of chapter 9 (the "risk" chapter) of the 
dioxin reassessment that "the weight of the evidence suggests concern for 
the impact of these chemicals on humans at or near current background 
levels."
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DeVito, M.J., Birnbaum, L.S., Farland, W.H., and Gasiewicz, T.A. (1995).  
Comparisons of estimated human body burdens of dioxinlike chemicals and 
TCDD body burdens in experimentally exposed animals.  Environ. Health 
Persp. 103(9): 820-831 (1995).
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*       "One way to determine the strength of an association between 
	dioxin exposure and a toxic effect in humans would be to 
	compare the dose of dioxin that is required to produce an 
	effect in animals to the dose of dioxin in humans that is 
	associated with a similar toxic effect.  While it is clear 
	that for some toxic effects, such as lethality and body weight loss, 
	there are marked species differences to susceptibility to 
	dioxins, many recent studies have also noted that for other 
	endpoints, such as reproductive and developmental effects, most 
	animal species respond at similar doses. Thus, the dose of 
	dioxin that produces a particular effect in experimental 
	animals might be expected to be similar to the dose of dioxin 
	associated with that same effect in humans."
 
*       "Here  we compare the body burdens of dioxins that produce 
	effects in experimental animals to the body burdens associated with 
	effects in humans, based on the clinical findings observed  during 
	epidemiological studies."
 
*       "A comparison of the in-vitro effects of dioxins on human and 
	animal tissues and cell cultures  . . . suggests that some of the 
	effects observed in experimental animals also occur in humans and that
 	the body  burdens of dioxins associated with these effects (adaptive 
	and/or toxic) are  similar between animals and humans."
 
*       "The current average  background' body burden of dioxin, furans 
	and dioxin-like PCBs    [expressed as toxic-equivalents (TEQs)] of the 
	U.S. population is 18-540 times less than        human TEQ body burdens 
	estimated from the studies that associated dioxin exposure with  
	increased cancer incidences."
 
*       "This average'background' body burden is 'only 3.2 times' lower 
	than the body burdens of rhesus monkeys whose offspring showed 
	behavioral effects after perinatal dioxin exposure."
 
*       "Enhanced viral susceptibility, as measured by increased 
	mortality, occurs in mice at body burdens which are equivalent to the 
	body burden seen in unexposed humans.'"
 
*       "Increased incidence of endometriosis in rhesus monkeys and 
	decreased sperm count in offspring of' rats treated with TCDD 
	occur at body burdens approximately five times that of unexposed 
	human populations."
 
*       "Effects in humans for which a causal relationship has been 
	definitively proven include chloracne, downregulation of epidermal 
	growth factor receptor, induction of CYP1A1 (maximal effect), induction 
	of liver CYP1A1 (LOEL), and hepatic sequestration. The range of body 
	burdens that result in chloracne in humans (96-3,000 ng TEQ/kg body 
	weight) and animals (23-13 900 ng TCDD/kg body weight) are similar.  It 
	should be noted that the first of these ranges represents 
	interindividual variation while the second includes interspecies 
	variation.  (Note: This latter sentence is very important in that it 
	emphasizes that people vary greatly in their sensitivity to proven 
 	dioxin effects, e.g., by a factor of 30-fold.)  The lowest observable 
	effect level (LOEL) for enzyme induction in animals is 1 and 23 ng 
	TCDD/kg body weight  in rats and mice, respectively,  which is within 
	the range of background human body burdens of 13 ng TEQ/kg body weight."
 
 
*       "[E]ffects associated with dioxin exposure for which a causal 
	link has not been definitively proven . . . include . . . decreased 
	birth weight, decreased growth, delayed developmental milestones, 
	cancer, decreased testosterone levels, and increased risk of diabetes. 
	These effects are  listed in  Table 3: Responses in Humans 
	Causally Associated with Exposure to Dioxins and Comparable Effects 
	in Experimental Animals, in which two additional responses,  tumor      
	production and object learning, are also listed."
 
*       "[I]n a National Institute of Occupational Safety and Health 
	(NIOSH) cohort . . . [t]here was a decrease in testosterone 
	concentrations in individuals with serum concentrations of TCDD as     
	low as 20 ppt at the time of tissue sampling, which is 3-4 times 
	background TCDD levels and only a 33% increase over total average 
	body burdens . . . [I]f decreased testosterone is due to dioxin 
	toxicity, then some humans may be approximately 280 times more 
	sensitive than are rats for dioxin-induced decreases in testosterone."
 
*       "Increased incidence of diabetes in [human] populations exposed 
	to dioxins has been reported in two studies with body burdens ranging 
	from 99 to 140 ng TEQ/kg."
 
*       "The present study indicates that humans and rats are equally 
	sensitive to TCDD-induced biochemical changes when compared on a 
	total body burden."
 
*       "Many of  the effects of TCDD have been studied following an 
	acute exposure in experimental animals.  In contrast, humans receive 
	low daily doses of these chemicals.  One of the assumptions in 
	extrapolating these effects to humans is that the effects are solely 
	related to  body burdens.   . . .[E]ffects such as cancer are clearly 
	related to both dose and time.  It is possible that in addition 
	to dose and body burden, length of exposure may also have a significant 
	effect on toxicity."
 
*       " . . . the background level used in this evaluation (13 ng 
	TEQ/kg body weight) is an average background.  Body burdens of
	dioxins appear to be log-normally distributed in humans, thus it would 
	not be unusual to see populations with body burdens three to four 
	standard deviations beyond the mean body burden.  Recent studies in the 
	Netherlands indicate that plasma TEQ concentrations in the 95th 
	percentile of the population are twice that of the mean, suggesting  
	that at least 5% of the population has two times the mean body burden.
  	In addition, there are subpopulations such as subsistence fishermen who 
	are likely to have much greater body burdens.  There are also some 
	toxic effects such as endometriosis and increased viral sensitivity, 
	which occur in experimental animals at body burdens less than 10 times 
	the average background exposures to humans.  Finally, human exposures 
	that result in adverse health effects, such as chloracne, decreased 
	birth weights, developmental delays, and cancer are 3-540 times the 
	present average background exposure to these chemicals.  Nevertheless,
        the available data indicate that high-level human exposure to dioxins 
	produce adverse health effects and that humans are a sensitive species 
	to the toxic effects of dioxins. Whether these low-dose effects are 
	occurring in the general population or the more highly exposed 
	subpopulations remains to be determined."
 
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