|
-, JPN 16 '99 07~29PM DOWELRNCO 30813E ~,0'?5 ~_
<br />Comparative Toxicology of Various Chlorinated
<br />Dioxins as Related to Chemical Structure
<br />MARGUERITE t. LENG ,
<br />IfraGh and Fnr;ron.•,vnra! Se;rnea, Thr Dow C7umieaf Ce,npany. M;dfand, Michitan. USA I86~t0.
<br />
<br />SLA4IARY
<br />''Eae generic term "dioxin" pertains to a family of compounds which are
<br />structurally similar but vastlq different in toxicity. It is often used
<br />incorrect'ly~ to designate one member of the falai7y, 2,3,7,8-tetrachlorodi-
<br />benzo-p-dioxin (TODD). There are 75 possible polychlorinated dibenzo-p-
<br />dioxine (PCDDs) with a million-fold spread in the dosage level required
<br />to kill laboratory animals. Those with four or five chlorines located at
<br />all four lateral positions (2,3,7 and 8) are extremely toxic. The toxi-
<br />city is progressively decreased by moving one or more chlorines to peri
<br />positioaa (1,4,6 or 9), and/or by having fever or morn positions substi-
<br />tuted. Dnta are reviewed from a number of studies demonstrating this,
<br />relationship. The relative hazard from potential exposure to the highly
<br />tozic 2,3,7,8-TCDD is also discussed.
<br />` FORMATION OF DIOXINS
<br />J Lov levels of polychlorinated dibeazo-p`dioxins (PCDDs) can be formed as
<br />byproducts during the manufacture of chloropheaols under alkaline condi-
<br />_ Lions at elevated temperatures and high pressures. The raa:tion is a
<br />two-step process involving bimolecular condensation of chlorophenates
<br />fo]loved by internal ring closure. The number cad position of the
<br />chlorine subetituents on the dioxins depend on the chlorophenates precept
<br />is the reaction mixture.
<br />For eicample, trace amounts of the highl,Y toxic 2,3,7,8-tetrachlorodibenzo-
<br />p-dioxin (TODD) are formed during the manufacture of 2,4,g-trichlorophenol
<br />by alkaline hydrOxysia of I,2,4,g-tetrachlorobenzene (Figure 1). This
<br />l TCDD can be carried through into products made from 2,4,5-trichlorophenol,
<br />1 such as 2,4,g-trichlorophenoryacetic acid (2,k,5-T) sad hexaehlorophene•
<br />[2,2'-methylene bie (3,4,6-trichloropheaol))• Similarly, condensation of
<br />2,4,6-trichlorophenate during its manufacture under alkaline conditions
<br />produces the expected 1,3,6,8-TCDD, as veil ae the isomeric 1,3,7,9-TODD
<br />by Smiles rearrangement (Figure 2). On the other hand, the expected 2,T-
<br />dichloro iaomar is not likely Eorned by condensation of 2,L-dichlorophepate
<br />under the acid conditions used in its manufacture by chlorination of
<br />phenol (Figure 3)•
<br />_! *Presented at Symposium of Collaborative International Pesticides
<br />Analytical Council (CIPAC), Baltimore, Maryland, June 7, 1979.
<br />Published in CIPAC Proceedings Symposium Series 1, W. R. Bontoyan,
<br />editor, 1979: Available from Heifers Printers Ltd., Kings Hedge's
<br />Road, Cambridge, CB4 2HQ, England.
<br />
|