(Fwd) Great Dioxin Info.

[Pawel Gluszynski <uugluszy@cyf-kr.edu.pl>]

Very useful excerpts from a PEERREVIEWED article by DeVito,
Birnbaum, et al. (1995) 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."  
 
*  "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 "8-540 times less than human TEQ 
   body burdens estimated from the studies that associated dioxin 
   exposure with increased cancer incidence."  
 
*  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 fro 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.  ... Effects 
   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.
 
(DeVito et al. 1995) 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(3): 
820-831.

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