Document BRoE62qZ89oXX8zy5M4QOD1jE

O t.% * --- *From M onsanto Ch em ica l Com pany At- S t . L o u i s , Mo. Date June 12# 1956 GfW Mr. H.K. Nason-M.O. 31 Mr. R.E. Soden-Nitro Mr. L.C. Weger-Nitro^J To Dr. R. Emmet Kelly to Medical' Dept. Reference Subject AT BADISCHEN ANILIN ICHLORPHENOL Persons Present: Dr. H. Oettel Dr. H. T . Hofmann `r A. Palm (Ph.D.) W. Soenksen (Plant Supt., part-time) On the 17th of November, 1953> Badische was producing a batch of trichlorphenol from tetrachlorbenzene when the process exceeded control pressure and temperatures similar to our Incident at Nitro. No one Was injured at the time. Within one week, as clean-up was being carried out, the first cases of chloracne developed. Fifteen or sixteen cases (6 serious)- developed within the next 1-2 months and additional cases showed up during the next 10-12 months until there -was a total of 50-60 cases. I did not see our most severe Nitro cases nor have I seen photographs of these cases. The photographs of the worst Badische cases show * horrible skin eruptions with nearly blister-like welts and some ulcera tion where infection ensued. Areas involved included the face, neck, arms, and upper half of the body. It is my impression that their severe cases were much worse than ours. In addition to the skin mani festations, their men reported all the additional symptoms as exper iences in our workers, i.e, fatigue, vertigo, loss of libido, painful Joints, etc. About ten days following the incident, and after initial clean-up-, Dr. Oettel was asked to expose animals to the workroom atmosphere. Rab bits (in open wire cages) were placed In the operating area for 24-^8 hours. There were.no obvious symptoms which developed in the animals until one week after exposure - when they died. Autopsy showed liver necrosis. Oettel thought there might be virus Infection or some other cause for death until he exposed additional animals In the department, others in cages suspended inside the "decontaminated" autoclave, and some In the adjacent department. All died within 1-2 weeks following 'exposure. Subsequently, animals placed in the cages v;hich had pre viously been in the department died of liver necrosis. A thorough systematic investigation has isolated Impurities in the trichlorphenol process (or residues) which will cause tne same effects in rabbits. Liver necrosis will develop In rabbits at the following doses of the indicated materials: 15-20 mg. of pentachlor naphthalene 1 mg. of chlorinated diphenyl oxide 0 .1 mg. of' residue from trichlorphenol distillation 0.01 mg. of residue fraction from trichlorphenol (above 230C) I `X---# - . 1 *T ~ --T'f~ >7 iXE C15579 2- - Dr. Oettel believes that the most potent chloracnogen is a compound* somewhat similar to chlorinated diphenyl oxide, /---- - j----. / but probably with additional oxygen atoms in the molecules. He has cor responded with Don-.Irish at- Dow who either reached the same conclusion independently or, m mentioning the potential of chlorinateddiphenyl oxide, influenced Oettel*s reasoning. .Oettel believes, further, that this impurity can show up In the production of any chlorinated phenols and is probably responsible for any chloracne which has been, due allegedly to chlornapthalenes, pentachlorphenol, chlorinated biphenyls, etc. Dr. Oettel has no faith in any animal skin tests for Isolating chloracnogens. He was- very interested In Kettering's work and was not aware of the publication referred to in Dr. Suskind's first report and which describes the cyclic skin development in new-born rats. (Refer- . ence: Parnell, J.P.: Postnatal Development and Functional Histology of the Sebaceous Glands in the Rat, Am. J. Anat., 85*^1/ 19^9.) He is convinced that the Bromsulphaleln test reported in the attached reprint Is significant. In this regard, Badlsche routinely uses this test on each batch of trichlorphenol which they now purchase from-Bayer, and refuses to accept material which fails to pass the animal tests. (I also learned at Bayer that they have experienced chloracne during the production of trichlorphenol but "have now licked the problem" according to Dr. Hansen (chemist - Research Director At ElberfeldJrT Badlsche ha3 been able to reproduce In the laboratory the conditions, which lead to the incident such as theirs and ours at Nitro and was quite surprised that v;e had not been able to do so. I was not given the Nitro process information, I.e., temperatures and pressures, but if I had had this information I am sure that I could have obtained Badlsche*s. One of their chemists, a Dr. Palm, sat in bn our dis cussions and was prepared to go into details. He did mention that "with 3 mols of trichlorphenol, methyl alcohol, and alkali, and a tem perature of l80CM the process gets out of control. His remarks are in quotes because he does not speak English and I*m not certain of his remarks. Dr. Oettel would be very happy to receive samples of any of our materials for investigation. He would like particularly: (1) Samples of any of the materials Involved in our 19^9 incident including tetrachlorbenzene, trichlorphenol, or Na salt and any residues from the autoclave or material cleaned from the equipment and structural members. (2) -Trichlorphenol (or Na salt) from regular production. (3) Any samples from raw materials, Intermediates, and final product which may have been involved in our cases which developed during our normal 2,4,5-T production in the years following the Initial incident. GNFTOE^ C1.5580 . 3- - He would be happy to exchange freely any and all Information with Us and Kettering. It was my suggestion that this be direct with Dr. Suskind to eliminate "third parties." He would routinely send carbons of any correspondence to us and we could request Dr. Suskind to do likewise. It is my opinion that this might save unnecessary duplication of effort and expense. In addition, Kettering might obtain* valuable information to further their Investigation involving human volunteers. I left with Dr. Oettel copies of the following: -r (1) The five (5) reports from the Industrial Hygiene Foundation which discuss their rabbit ear tests. (2) Kettering's report - ''Clinical and Environmental Survey at Nitro, 1953." (3) Kettering's report - "Environmental Survey Carried Out In Building 30, Monsanto Chemical Company at Nitro, February 2, 1956." We reviewed thoroughly Mr. Weger's excellent "Hiatory of Chloracne" which he sent to me with covering memo dated Mayw 15, 1956, and which included descriptions of Kettering's reports on their human and animal research. I did not give Dr. Oettel a copy of this account because I did not have permission to do so. As a result of my visit, It may be desirable to edit this report somewhat and add further process information before forwarding this to Badische. Any specific recommendations are implied In the above narrative account of my visit to Badische and must be based on an agreement that full and complete exchange of information with Badische is desirable and possible. EPWrdh Attachment Elmer P. Wheeler C15581