III. Edematous Cyst Covering Rump. 21-day Embryo. 0.02 μg (micrograms), 2,3,6,7-Tetrachloro-dibenzo-p-dioxin. Senator HART. The hour being 12:25, I suggest we recess until 2:15. (Whereupon, at 12:25 p.m., the hearing was recessed, to reconvene at 2:15 p.m. this same day.) AFTERNOON SESSION Senator HART. We resume this afternoon to hear first from Dr. Julius Johnson of the Dow Chemical Co. If a corporate entity can have a spirit attached to it, the comparing is a distinguished corporate constituent of mine. STATEMENT OF DR. JULIUS E. JOHNSON, VICE PRESIDENT AND DIRECTOR OF RESEARCH, THE DOW CHEMICAL CO.; ACCOMPANIED BY ETCYL BLAIR, DIRECTOR OF DOW AGRICULTURAL CHEMICAL RESEARCH; V. K. ROWE, DIRECTOR OF THE DOW TOXICOLOGICAL LABORATORY; AND GEORGE LYNN, DIRECTOR OF GOVERNMENT REGULATORY RELATIONS OF THE DOW CHEMICAL CO. Dr. JOHNSON. Thank you, Senator Hart. I have with me Dr. Blair, director of Dow Agricultural Chemical Research, Mr. Rowe, director of our Toxicological Laboratory, and Mr. George Lynn, director of our Government Regulatory Relations. Senator HART. Thank you. You are all welcome. Doctor, you have given us a statement. We will order it printed in full in the record and as you go along, if there is any extension or summation you care to make, the record will contain the full statement in any event. Dr. JOHNSON. Senator Hart, the policy decision has already been made and announced this morning. I will, however, with your permission, read my testimony, all except the last part which deals with some historical matters that already appears in the record. Then, if you would permit, I would like to make some additional comments which may be appropriate to the process of shortening the time interval between the discovery of a suspected toxic phenomena and taking appropriate action. I would also like to refer back to some earlier work done under Senator Ribicoff's guidance in his committee and quote at least one passage from that work published in 1966, which I think is appropriate to the issue, if I may do so. Senator HART. By all means. Dr. JOHNSON. Thank you. Mr. Chairman, I am Julius E. Johnson, vice president and director of Research and Development of the Dow Chemical Co., Midland, Mich. I also served as a member of the Secretary's Commission on Pesticides and Their Relationship to Environmental Health, May 8, 1969, to November 7, 1969, chairman, Emil M. Mrak. I have with me George Lynn, director of Government Regulatory Relations of the Dow Chemical Co. V. K. Rowe, director of the Dow Toxicological Laboratory and Etcyl Blair, director of Dow Agricultural Chemical Research, are also present to assist if necessary. This statement is concerned with the herbicide 2,4,5-trichloroxyacetic acid, which has often been referred to as 2,4,5-T and the chemical intermediate 2,4,5-trichlorophenol used in the manufacture of 2,4,5-T. An announcement was issued October 29, 1969, by Dr. Lee Dubridge of the Office of Science and Technology which referred to birth defects observed in tests by the Bionetics Laboratories using 2,4,5-T in various dosage ranges in mice and rats. This announcement preceded the final report of the Panel on Teratology of the Mrak Commission appointed by Secretary Finch which, since May 8, 1969, had been reviewing the effects of pesticides upon health and the quality of environment. At the time, October 29, 1969, members of the Mrak Commission had not seen the Bionetics report on teratology. Following the announcement by the Office of Science and Technology, I became particularly concerned because Dow is a manufacturer of this herbicide. Consequently, I made a diligent effort to trace the source of samples used and learned that the 2,4,5-T sample came from the Diamond Alkali Co. (which no longer makes 2,4,5-T). Moreover it was learned that 2,4,5-trichlorophenol also tested by the Bionetics Laboratory came from Coleman-Mathison-Bell who had obtained the sample from McKesson-Robbins who in turn had procured it from the Dow Chemical Co. 2,4,5-trichlorophenol is used as an intermediate in the manufacture of 2,4,5-T. Hence, the quality of 2,4,5-T is related to the quality of its intermediate 2,4,5-trichlorophenol. The chemical process used by Dow for manufacture is as follows: 1,2,4,5-tetrachlorobenzene is hydrolyzed in a solution of methanol and sodium hydroxide in water to form sodium 2,4,5-trichlorophenate. This is in turn reacted with sodium monochloroacetate to form sodium 2,4,5-trichlorophenoxyacetate. The solution is acidified to precipitate and recover the 2,4,5-trichlorophenoxyacetic acid. Since 1950 we have been keenly aware of the possibility of a highly toxic impurity being formed in 2,4,5-trichlorophenol as a side reaction under conditions of elevated processing temperatures. The most sensitive toxic reaction observed in humans to this impurity was manifested by a condition known as chloracne, a skin disorder mostly prevalent on the face, neck, and back. It is similar in appearance to severe acne often suffered by teenagers. We also knew that if the impurity was present in the 2,4,5trichlorophenol it could be carried forward to the end product, 2,4,5-T. It is not formed during the manufacture of Dow 2,4,5-T from the 2,4,5-trichlorophenol, nor does it form on storage even at high temperatures. To avoid the impurity in 2,4,5-T it is necessary to keep it out of the 2,4,5-trichlorophenol. Our early control test was a bioassay. This consists of applying a solution of the material to the inner surface of a rabbit's ear and observing for the typical skin response described in a paper published in 1941 by Dow scientists. I wish to insert in the record at this point the paper entitled "The Response of Rabbit Skin to Compounds Reported to have cause Acneform Dermatitis," by E. M. Adams, D. D. Irish, H. C. Spencer, and V. K. Rowe, published in Industrial Medicine, January 1941. Senator HART. It will be printed. (The information follows:) The Response of Rabbit Skin to Compounds Reported to T Have Caused Acneform Dermatitis E. M. ADAMS, D. D. IRISH, H. C. SPENCER, Biochemical Research Laboratory, HOSE of us acquainted with the industrial field have recognized the need of an experimental method for studying skin irritation. We would profit greatly by knowing the potential skin hazards of a substance before it is put into use; we would be able to take proper precautions in the cheapest and most satisfactory manner and many undesirable incidences could be avoided. In the literature there are many instances of irritation tests upon the skin of animals, but apparently there has not been a comprehensive study. In an attempt to develop an experimental method, we began about six years ago to study the responses of rabbits' skin to various types of substances. We considered the possibility that if enough were known of these responses to different types of compounds, particularly to those with which there has been considerable human experience, then these responses could be organized to form the basis of an experimental method. Acneform dermatitis, characterized by such lesions as folliculitis, comedones, nodules, papules. pustules, and inflammatory changes, has been reported arising from exposure to quite varied substances including petroleum oils and greases, shale oil, paraffin, zinc oxide, chlorine, tars. pitches, chlorinated diphenyls, chlorinated naphthalenes, and crude chlorinated phenols1 21 8 9 10 12 13 14 18 24 27. 18. 28 30 32, 23, 24, 27. 28. 29. 30. 32. 33. 34. The recent occurrence in this country of such an acneform eruption, ** 12 13 sometimes called "chloraene." has attracted particular interest, and we meluded in our animal studies five types of substances known to cause the reaction Today we wish to describe the unusual response of the rabbits' skin to these materials and to consider its possible significance. Experimental Part OUR experiments, materials have been ap I plied to the inner surface of the ear of albind rabbits and to the shaven belly. The undiluted materials have been used as well as solutions of various concentrations in olive oil, paraffin oil US P. propylene glycol, ethanol and water. Liberal applications were made on the ear with 2 covering The applications on the abd men were made in a small cotton pad which Was cetered by a large bandage of filter cloth Jela place by adhes ve tape Applic, tops were Sy days a week t four ion of some hundreds of test substances are easily arranged according to type. Certain of the strongest irritants produce a rapid destruction of the tissue (necrosis), without the skin having an opportunity to show an active response. Irritants with milder and slower actions than this have some effect upon the tissues, as a result of which we see certain responses on the part of the tissue. Most irritants have resulted ir responses in the rabbits' skin which tend to develop rapidly and to subside in a short time. This relatively rapid response, which we have termed a simple irritation or reaction, may include, depending upon the severity, any of the following: hyperemia, congestion, inflammation, exfoliation, edema, blistering, sloughing, exudation, crustation, necrosis, induration, hair loss. Microscopically one may see hyperemia, congestion, hemorrhage, edema, blistering, leucocytic infiltration, sloughing, and various degenerative changes. One type of response has been observed, however, which requires a somewhat longer interval in which to become apparent, and which has a much more prolonged course. This latent reaction is a proliferative response which may possibly occur in any of the structures of the skin, but that about which we are particularly concerned now Is epithelial hyperplasia, with its resultant thickening of the skin, follicle enlargement and sequellae. Naturally responses vary to some extent, and we have observed various combinations of these reactions, depending upon the substances applied to the skin and the intensity of action. For purposes of classification we have arbitarily divided the proliferative response into the following five groups according to intensity: 1. Least detectable. 2. Very slight. 3. Slight 4. Moderate. 5. Severe. While there are naturally no sharp breaks between these and some overlapping occurs, division was rather easy and has been very useful. Least detectable epithelial hyperplasia: This degree of response is manifest as an increased prominence of the hair follicles on the inside of the ear The little dots that one sees on the inside of the car simply become slightly larger. After WORKS AR art a marked reaction res, ted are ended this enlargement regresses osperses céramed following the applica washit time leaving the skin apparently normal |