Document gaowwzG7NgnQjd4OrvgawG0rV

`MJiivlOiC/ifti*Uiii TO nircct^cT j;11:115 nir.uc: iii'.-m .tti s. Lr-.u<ut:. 11: j u t k : I'iitrch 1, 1077 - i-KOM Acting Asscciote Director .Research Resources Program sui-iKcr Studies 0:1 Possible Feiitadilorciphznol/Pibauzodioxin Intoxication (Progross Report) The Rational Institute of rnviron.T.antru Health Sciences (Dr. Moore) was contacted by Mr. George l.t-Munyan in December 197'-. Mr. LeMuny-m owns a dairy faro in Cedar Springs, Migiiiyan. His faro was one which lost all of its cattle during the Michigan PUS incident a couple of years ago. In'addi tic>n,* his faro buildings had burned soon after this incident. He , constructed ns;/ barn facilities and rcpcpulafced his faro with dairy cattle frev.n another statu, for several months after this re-population, his operation from a herd health standpoint was fairly npna?l. After these first few Months, however, he started experiencing various types of problems which included calf loss, illness and death in adult animals, ajid loss of nil':-production. These losses continued through 1975. Late in'1970, several animals from the LeHunyan .herd were transported to the Veterinary Clinic of Michigan State University for surveillance and evaluation. Tissues fro.u one of thesu animals collected at the time of necropsy weru evaluated for the presence of a number of chemical toxicants The iexults of this evaluation revealed the presence of pcntachloropiu-nol (PCP). in the purts-pcr-billion range. Mr. LeMuny;:.: contacted rev v/; see if I could offer any suggestions or assistance. I discussed thi: fanr.Is problem with Pr David Ellis of Michigan State University with a focus not on pentnchlorfiphanol intoxication per se, but an innttoo;xication that could *be a ccosoqi&nce of chemical contaminant associated '.nth PCP; i .c., dibenzodioxins and dibenzofuransf In early January 1977, while in Lansing, Michigan, to attend a TP? meeting, I traveled to the'LeMunyan farm '*ith D::s. Ellis end Davis (Michigan Dept of Ayrculture). It was agreed that one had to rioteruino if the PCP exposure found in the one animal was an isolated i.v.tance or a Generalizod circumsUnce. To this end. v;a bled a number of ill ani:;*tls. HSU had the blood samples evaluated fur the presence or pentachlorophoiiol, which was'found in most every instance. The level or PC!1 d;-:lectc-.! is not of sufficient magnitud:: to be of prime toxicologic concern; if did indicate continual o:ul chronic exposure lo PCP (through treated lumber in th*: now Morn). The chronic exporcr? r.vJerscorns 1!:e potential 'or nccurrmulotior. oi dibeuzndiuxins and dibnnzufurans which could :L* of toxicologic i:icai!r:'i. I agreed to have tissues From animals evaluated for the proson-.:* of diboaxodioxin at iilFJiS. Tissues (liver and fat) Pxep- Cl8543 were 'sen!:'-to u'lriJS as was a- piece of treated lumber from the barn. DibonzodiDzins r.eri only br; detected Un\);jgh"GC/M5 methodologies, tin analytic?: method clearly within our cnpabilitics and experience. We observed Lhe presence oT octa-CDU and hep ta-CIJ;') in the wood sample. Analyses"of liver tissues (after extensive efforts to develop an effective extraction procedure suitable for the higher chlorinated dibonzodioxins) confirmed the presence of dibonzvdioxins in 15 of 15 livers. Ocv.adioxin values are in the pnrts-por-billion range with decreasing incidence and levels of hep tadtoxins and three instances of hexadioxins in the partr.per-1ri 11 ion ranga. These analyses are 'not yet cor.?lets. Jn my opinion, the presence of these dibenzodioxins (and likely equivalent amounts of the toxic dibanxofurans, although'we have not assayed for these) is of prime toxicologic.importance. P^o^ipus work at NIFHS has shown that the hexa-CbD present (i.c., 12,3,irTSTwi) is a most toxic dibenzodioxin isomer with a single oral LD50 in guinea-pigs of less than 100 ug/kg. Although the heptachlorinaled dibonzedioxin present (1>2,3,4,6,7 has not received thorough toxicologic evaluation, its structure is such 'that one would predict it to have significant toxicologic properties. The octachlorinated dibenzodioxins have been reported by many to be of little or diminished toxicologic significance. This is based in large part upon its extremely poor solubility and consequent lad: of absorption. Studies with this compound are all seriously flawed in one way or another, chfonic toxicity of cofca-CDD has not bean properly evaluated. The * "poor" absorption and therefore diminished toxicity cannot be reassuring in-this circumstance since v;e are detecting it in liver. Its possible - toxicity cannot be ignored. Early attempts to analyze fat for these compounds has been unsatisfactory. Most of the "fat samples" failed to yield much extractable lipid indicating that the majority of tissue submitted is of connective tissue origin (this reflects possible cachexia). Where sufficient lipid was extracted, early analyses suggest that dibenzodioxin levels in this tissue nay be orie to tw o magnitudes greater than that, found in liver. One of the high values detected was frOiTi a young calf liver which, I believe, had be:n allowed to-drink iniIk produced cn the farm. Previous work at !IEHS. with `ICDO showed this chemical to be readily secreted in the milk. One must consider the possibility that the excessive calf - mortality experienced at the LeMunyeu farm may be due to the dibenzodioxins received in milk. Summary' This irjrfe-4^-j.Eu*.y-Of4-ii+ou-tfrfr-firstrronftmrd~rn.*rc< This work is in my opinion the first confirmed instance of the presence .of dihenzodic^IiiS in animal tissues as a likely consequence- of chronic exposure to PC? treated wood, it ha:; been mentioned to me by a number of practicing v-: :-;rinarians that this circumstance, although clearly unusual in its severity, may not be a unique situation. The public health imp!icotions are somewhat obvious: C1854 i 1. Possible po; ilation exposure to dibenzodio;;ir! <w:d dibenzofuran contaminants through use of PCf* or treated lumber. 2. Possible presence of these toxic contaminants in conmercial mill:. 3. The presence of these impurities in meat products. Mote The LcMunyan hard is one which has had extensive press exposure. These John A. Moore, D.V.M. -00148V6---- 1HrR- Cl8545 rr