A publication of Work On Waste USA, Inc., 82 Judson, Canton, NY 13617 315-379-9200 October 17, 1991

Report on “Dioxin levels in blood of municipal incinerator workers”, by A.J. Schecter, et al, Med. Sci. Res., 1991, pgs. 331-332. Reprints of this article are available from: Dr. Paul W. Brandt-Rauf, Div. of Environmental Sciences, Columbia University, 60 Haven Ave., B-1, NY, NY 10032.

“...Municipal incinerator workers, in the course of their work, have considerable exposure to incinerator ash, and this raises the possibility that some of these workers might absorb significant quantities of these PCDDs and PCDFs. As a first attempt to try to assess this possibility, we have determined the levels of PCDDs and PCDFs in pooled blood samples from 56 municipal incinerator workers and 14 unexposed controls. Selected employees of three municipal solid waste incinerators had been previously enrolled in a study to investigate potential worker exposure to lead from ash. The greatest potential for exposure to the toxic components of ash occurs during ash cleaning operations...A contribution from work-place exposure can be suspected, however, since the pattern of congeners in the blood in this case was more similar to the typical pattern of congeners found in incinerator ash than to the patterns seen from other exposures such as phenoxy-herbicides (where 245-T and 2378-TCDD levels are raised) or in paper and pulp bleaching (where 2378-TCDD and 2378-TCDF levels are raised)...these findings, if substantiated, suggest that significant alterations may be called for in work practices and the design of municipal incinerators and the handling of their effluents (in particular the ash) to protect incinerator workers and the general populace near incinerators and ash land fills. For example, the Dutch government has had to ban general consumption of some milk and meat products from cattle grazing near municipal incinera- tors, following documentation of elevated dioxin levels in such products. Clearly, further investigation of this issue is indicated.”

Comments on the 11th International Symposium on Chlorinated Dioxins and Related Compounds. By Tom Webster of the Center for the Biology of Natural Systems. Despite the front page news stories of the last year proclaiming that dioxin was much less of a problem than previously thought, much of the evidence for this position was largely absent or even contradicted at this year’s international scientific meeting held September 23-27 in Research Triangle Park, North Carolina.

Vernon Houk doesn’t defend his views

Dr. Vernon Houk of the Centers for Disease Control, widely quoted for his views that the risk of dioxin to humans is overstated, failed to make his scheduled presentation at the conference. Stand-in Dr. Pirkle presented no evidence to back-up Houk’s claim and offered to deliver any “potentially lethal questions” to Houk himself. Department of Veteran’s Affairs scientist Dr. Kang’s analysis of past studies on soft tissue sarcoma was taken apart on the spot. The lead critique came from Dr. Marilyn Fingerhut, prime author of the NIOSH study which found statistically significant increases in cancer in U.S. chemical workers exposed to dioxin containing compounds. German epidemiologist A. Manz reported statistically significant increases in cancer in the chemical workers exposed at the Boehringer plant [see Waste Not 170]. The qualitative evidence for dioxin as a human carcinogen is clearly growing. Furthermore, according to separate analyses of the NIOSH data by T. Webster and the California Department of Health Sciences, dioxin's potency -- a quantitative measure of carcinogenicity-- may not be too different in humans from that derived from animal studies.

Simple receptor threshold model refuted

Both human epidemiology and animal cancer bioassays necessarily describe relatively high dose regimes. Risk assessors rely on mathematical models to predict effects at the lower doses more commonly found in the environment. The EPA’s current “acceptable” dose of dioxin is computed from experiments on rats extrapolated to low doses using a model which is linear at low doses with no threshold. There has been pressure on EPA to abandon this position for some time. A potential alternative was discussed at the October 1990 Banbury conference (infamous for the claim by an industry co-sponsor that “consensus” was reached that the risks of dioxin were overstated). Most and possibly all of the biological effects on dioxin-like compounds are mediated by the Ah receptor. Binding of dioxin-like compounds to this molecule changes the expression of various genes, the most well known being induction of the enzymes PA501A1 and P4501A2. This might form the basis for devising a new model for the risks from dioxin. In particular, some Banbury attendees claimed that this receptor mechanism meant that dioxin-like compounds had a threshold, i.e., that exposure below a certain dose had no biological effect.

The idea of building a new risk model on the interaction of dioxin-like compounds with the receptor caught on. The USEPA announced in April 1991 that it would re-evaluate their 1985 estimate of the cancer risk of dioxin. Later that month, the Washington State Health Department weakened its recommendations on consumption of fish from a lake contaminated by pulp mill effluents. Based on the unreferenced notion that 5% of the receptor must be bound to dioxin for any biological response -- including enyme induction-- to occur, they concluded that a dose over 3,000 times larger than EPA’s “acceptable” level would cause no biological effects and that levels 13,000 times higher might not cause any adverse effects.

Data presented at the International Symposium should lay such simple models to rest. Indeed, when the Washington State model was presented at this meeting, the author stated that it was no longer viable. (This has not, however, led to a change of the fish advisory in Washington State). Work at the National Institute of Environmental Health Sciences (NIEHS) by Lucier et al. on the dose response relationship for enzyme induction in the rat liver found no indication of a threshold for these effects. Indeed, P4501A1 induction appeared to match theoretical models indicating a linear response at low doses. The effect of dioxin on epidermal growth factor (EGF), an important peptide hormone, was similarly simple.

In a more sophisticated approach at a “biologically-based model,” NIEHS mathematician Portier used these data as indicators of the shape of the cancer dose-response curve for dioxin. He calculated “acceptable” doses of dioxin ranging from much less than the EPA’s current value to much greater. Since the mechanism by which dioxin causes cancer is not known, the relevance of these surrogates is unclear. Since dioxin is often presumed to be a tumor “promoter,” data on the dose response curves for cell proliferation and volume of pre-neoplastic foci (tumor precursors) in the rat liver were developed by NIEHS as well. However, these relationships are complicated and show great interindividual variation among laboratory animals. Other factors may further limit their application: 1) these data were generated using a dose of a known cancer initiator followed by dioxin; 2) liver cancer is not typically associated with dioxin exposure in humans.

Non-cancer effects capture increased attention

Transgenerational developmental effects and immune system alterations appear to be some of the most sensitive indicators of dioxin toxicity. Drs. Moore and Peterson of the University of Wisconsin described experiments in which a single low dose of dioxin given to pregnant rats caused permanent alterations in the sexual behavior and development of their male offspring. Dioxin inhibits production of the male sex hormone testosterone in the rat fetus during a crucial period of development. Behavioral and developmental effects of various kinds are widely noted in wildlife, with fetuses and young being more sensitive than adults.

TEFs and PCBs

Many compounds display dioxin-like activity. Their activity relative to 2,3,7,8-TCDD is rated using TCDD equivalents (TEFs) commonly extended to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans, TEFs are now being developed for certain polychlorinated biphenyls (PCBs) as well. Several co-planar PCBs were rated at 0.01 to 0.1, mon-ortho PCBs at about 0.001 and lower values for di-ortho PCBs. Studies of wildlife indicate that PCBs dominate the body burden of TCDD equivalents. Similar results were reported by Schecter et al. for humans, raising the total body burden of dioxin-like compounds significantly. Total level of dioxin-like compounds needs to be taken into account, especially if there is a threshold. Some of the neurological effects of PCBs do no correlate with TCDD equivalence, implying a different mechanism