RE: "other" dioxins

[Michael Hagen <HAGENM@epvan.dots.doe.ca>]

> Be careful.  The term dioxin can have two separate meanings. 1) It
> can refer to only 2,3,7,8-tetrachloro-dibenzo-p-dioxin, or 2) It can 
> be used to refer to all of the different chemical congeners within 
> the dioxins that have the same or similar toxicity levels as 
> 2,3,7,8-TCDD (also known as toxic equivalency factors/quotients
> -TEFs or TEQs).  This use of the term dioxin includes the
> dibenzofurans and PCBs--some of which are nearly as toxic as
> 2,3,7,8-TCDD.

Let's clarify a few things here.

"dioxin" refers to all or one of the 75 compounds consisting of two 
benzene rings joined by two oxygens and having at least one chlorine 
atom attached.  The congener 2,3,7,8-tetrachlorodibenzo-p-dioxin 
(T4CDD) is the most studied, best known, and most toxic.  "furans" are 
the 135 polychlorodibenzofurans consisting of two benzene rings joined 
by one oxygen.  "PCBs" are the 209 chlorinated compounds consisting of 
two benzene rings joined directly (i.e., no oxygens).

"TEQ" is the toxic equivalence of a mix of dioxin-like compounds 
(including the furans and PCBs) as T4CDD.  That is, the amount of 
T4CDD that would give the same toxicity as the mix.

"TEF" is the toxic equivalence factor used to convert the other toxic 
compounds to the equivalent amount of T4CDD.  For dioxins and furans, 
the conventional reference is:

NATO.  1988.  International Toxicity Equivalence Factor (I-TEF) method 
of risk assessment for complex mixtures of dioxins and related 
compounds.  Committee on the Challenge of Modern Society, #186.

Under this scheme, only the 17 dioxin and furan congeners with 
chlorine atoms at the 2, 3, 7, and 8 positions are considered toxic.  
The remaining 118 congeners are assigned a TEF of 0 (zero).  The TEFs 
for the toxic dioxin and furans are:

Dioxins		     TEF	       Furans		    TEF
2,3,7,8-T4CDD	     1.0	       2,3,7,8-T4CDF	    0.1
1,2,3,7,8-P5CDD	     0.5	       1,2,3,7,8-P5CDF	    0.05
1,2,3,4,7,8-H6CDD    0.1	       2,3,4,7,8-P5CDF	    0.5
1,2,3,6,7,8-H6CDD    0.1	       1,2,3,4,7,8-H6CDF    0.1
1,2,3,7,8,9-H6CDD    0.1	       1,2,3,6,7,8-H6CDF    0.1
1,2,3,4,7,8,9-H7CDD  0.01	       2,3,4,6,7,8-H6CDF    0.1	      
08CDD		     0.001	       1,2,3,7,8,9-H6CDF    0.1
		     		       1,2,3,4,6,7,8-H7CDF  0.01
		     		       1,2,3,4,7,8,9-H7CDF  0.01
		     		       O8CDF		    0.001

So, for example, if you had a sample which contained 5 pg/g T4CDD, 10 
pg/g P5CDD, 100 pg/g of the three H6CDDs, 200 pg/g O8CDD, and 50 pg/g 
T4CDF, you would have a TEQ of 5 + 5 + 10 + 0.2 + 5 = 25.2 pg/g.  
Which means that if you also had a sample with nothing but 25.2 pg/g 
T4CDD, the two samples have the same toxicity.

The TEFs for the PCBs are more controversial.  Three references are:

Ahlborg, et al.  1994.  Toxic equivlency factors for dioxin-like PCBs.  
Chemosphere 28, 1049-1067.

Safe, S.H.  1990.  Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins 
(PCDDs), dibenzofurans (PCDFs), and related compounds: environmental 
and mechanistic considerations which support the development of toxic 
equivalency factors.  CRC Crit. Rev. Toxicol., 21, 51-88.

Safe, S.H.  1994.  Polychlorinated biphenyls (PCBs): environmental 
impact, biochemical and toxic responses and implications for risk 
assessment.  CRC Crit. Rev. Toxicol., 24, 1-63.

Some TEFs are:

IUPAC	      Ahlborg et al.	  Safe (1990)	      Safe (1994)
77	      0.0005		  0.01		      0.01
126	      0.1		  0.1		      0.1
169	      0.01		  0.05		      0.05
105	      0.0001		  0.001		      0.001
114	      0.0005		  0.001		      0.002
118	      0.0001		  0.001		      0.001
123	      0.0001		  0.001		      0.00005
156	      0.0005		  0.001		      0.0004
157	      0.0005		  0.001		      0.0003
167	      0.00001		  0.001		        --
189	      0.0001		  0.001		        --
170	      0.0001		  0.00002	        --
180	      0.00001		  0.00002	        --


Okay.  Now for something REALLY scary:

In addition to the PCDDs, PCDFs, and PCBs, there are additional 
dioxin-like compounds for which little is known.  These are the 
polyhalogenated analogues of the above mentioned--i.e., with bromide 
or fluorine, or some combination of brominde, chlorine, and fluorine.  
These are rarer than the polychlorinated compounds, but may be equally 
as toxic.  Indications are that 2,3,7,8-polybromodibenzo-p-dioxin has 
a TEF of 1 or greater, for example.  The possible configuration of F, 
Cl, and Br in the 2, 3, 7, and 8 positions on dibenzo compounds 
numbers in the thousands.

There's more:

There also exist sulphur analogues of the dioxins and furans.  These 
are compounds with a sulphur bridge rather than an oxygen.  These 
thianthrenes and thiophenes may be equally as toxic as the oxygen 
equivalents.

After the bad news, maybe some good?

There are non-chlorinated dioxin-like compounds (known as 
endo-dioxins) which act in the same manner as dioxins in the body.  
That is, the toxic effect seems to be initiated by engaging the aryl 
hydrocarbon receptor (ArH).  These include heterocyclic aromatic 
amines (HAAs) and indole-3-carbinol (I3C).  I3C may have a TEF of 
0.0001.  HAAs are found in meat cooked at high temperatures (your 
char-broiled steak) and I3Cs are formed in the gastric tract from raw 
materials in Brassica vegetables (broccoli, cabbage, Brussels sprouts, 
cauliflower).  I3C, though acting in the same way as dioxins (I3C may 
alter male reproductive development in pregnant rats the same way as 
dioxins do (Wilker, et al., paper presented at Dioxin '95 in Edmonton, 
August, 1995)) are cancer-*inhibitors*.  The body burden of HAAs and 
I3C is millions of times higher than for dioxins and furans.

One intriguing thought:  our species has been subjected to a unique 
evolutionary pressure ever since homo erectus started eating charred 
meat in smokey caves 1 1/2 million years ago.  There are indications, 
for example, that chronic reactions to dioxin exposure such as 
chloracne or deformed fingernails are initiated in humans at doses 
hundreds of times higher than for some species of monkey.  So I 
wouldn't worry too much when it's reported that Big Macs have a TEQ 
that's 50 times higher than the EPA-proposed daily maximum dose . . .

Mike Hagen
hagenm@epvan.dots.doe.ca