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1756. Appraisal of isocyanate workers
272
THE CHEMICAL ENVIRONMENT
Cr vx with 5 ~o K2Cr207 in 1 Yo sodium lauryl sulphate. One group treated concurrently with an oral suspension of G 35905 S showed a higher incidence of sensitization than the control group. It is suggested in explanation that the drug may promote the reduction of hexavalent to trivalent Cr and thereby encourage protein-binding of the sensitizer. [To underline the importance of such studies of the complexities of chromium sensitization, we may perhaps refer to a report (H. Ebner, Dermatologica 1967, 135, 355) that of 8541 patients treated at a skin clinic during a period of 12 yr, over 9 ~ were found to be sensitized to Cr. The contact eczema of five of these patients was attributed to chromates present in clothing materials.] 1755. Lingering doubts over toluene and xylene Speck, B. & Moeschlin, S. (1968). Die Wirkung von Toluol, Xylol, Chloramphenicol und Thiouracil auf das Knochenmark. Experimentelle autoradiographische Studien mit aHThymidin. Schweiz. med. Wschr. 98, 1684. No depression of bone-marrow function, as measured by the uptake of tritium-labelled thymidine, and no decrease in the numbers of peripheral blood cells or variation in the differential leucocyte picture could be detected in rabbits after daily subcutaneous injections of toluene (I) or xylene (II), in doses of 300 mg/kg for 6 wk or 700 mg/kg for up to 9 wk. Neither I nor II increased the myelotoxic effect of concurrently administered busulphan (10 mg/kg/day for 2 wk), although one would anticipate that when busulphan is given with individual compounds in this way, any potentiation of its myelotoxicity would be readily detectable. The conclusion drawn from these findings is that the aplastic anaemia sometimes observed after long exposure to I or II is attributable to their contamination with benzene rather than to the methylated derivatives themselves. However, in parallel experiments, the authors failed to demonstrate the expected interference with DNA synthesis in the bone marrow by prolonged daily administration of chloramphenicol (500--750 mg/kg/day) or thiouracil (250-400 mg/kg/day), two recognized inducers of human agranulocytosis. It must also be remembered that a wide variation is found in the sensitivity of haemopoietic systems in different species, but it is significant that the same group obtained very different results with benzene in the same species and using the same test procedure, aplastic anaemia being induced by this solvent within 1-9 wk by daily subcutaneous doses of 300 mg/kg/day. In these animals, autoradiography revealed severe inhibition of DNA synthesis in the bone marrow (Cited in F.C.T. 1967, 5, 728). [In view of the ready absorption of toluene through the skin (Cited in F.C.T. 1968, 6, 546), it is encouraging to learn that, at least in the pure form, it may present less of a hazard than is sometimes supposed, but restraint must obviously be exercised in interpreting these findings in terms of the probable effects in man.] 1756. Appraisal of isocyanate workers Bruckner, H. C., Avery, S. B., Stetson, D. M., Dodson, V. N. & Ronayne, J. J. (1968). Clinical and immunologic appraisal of workers exposed to diisocyanates. Archs envir. Hlth 16, 619. It still remains to be established whether the pulmonary response to isocyanates is allergic in nature. Evidence so far has suggested that such a mechanism may operate in some cases (Cited in F.C.T. 1966, 4, 542). To throw further light on this, 44 employees of a company involved with isocyanates
THE CHEMICAL ENVIRONMENT
273
were examined clinically and immunologically and their working environment was assessed. Of these workers, 26 had experienced multiple exposure to isocyanates over periods of up to 11 yr. The remaining 18, who had never worked with isocyanates, served as the control group. The exposed workers were divided into three groups based on isocyanate exposure and the type of response experienced, namely 'minimal' reactors, 'overdose' responders and 'sensitized' reactors. Minimal responders were those who developed some symptoms of mucous-membrane irritation in the eye, mouth and throat, but experienced no bronchial disturbance and had no previous history of allergy. Overdose responders were exposed to higher concentrations and, in addition to mucous-membrane irritation, developed bronchial symptoms and headaches, but they rarely possessed any previous history of allergic disorders. Four of the five members of the exposed sensitized group had a history of allergy. Eye, nose and bronchial reactions, including audible wheezing, rapidly followed test exposure to minute airborne concentrations of isocyanates. No headaches were reported, but repetitive overdose responses were experienced prior to the development of an asthmatic reaction. When signs of sensitization initially developed, after periods of repetitive exposure ranging from 2 months to 5 yr, there was a latent period of up to I-6 hr between exposure and the appearance of asthmatic symptoms, but as the number of exposures increased the exposure-response interval shortened and marked bronchospastic symptoms appeared within seconds of exposure. It is concluded that the asthmatic syndrome occurring in some isocyanate workers is secondary either to a pharmacological overdose or to a hypersensitivity mechanism, with both mechanisms sometimes operating, especially if exposure to high concentrations occurs. 1757. Another matrimonial hazard?
Gerwig, T. & Winer, M. N. (1968). Radioactive jewelry as cause of cutaneous tumour. J. Am. med. Ass. 205, 595.
Radiodermatitis caused by the wearing of a radioactive gold wedding ring has already been reported (Simon & Harley, J. Am. reed. Ass. 1967, 200, 254). The authors cited above have now described a case of skin cancer due to the same cause. A 50-yr-old man complained of a lesion on his left ring finger. He had worn a particular ring on this finger for 10 yr, following its enlargement by a local jeweller in 1946, but then pruritis and discomfort led him to transfer it to his right hand. After a further 8 yr, similar symptoms developed in his right ring finger and in 1964 he stopped wearing the ring altogether. Biopsy of a nodule on the left ring finger showed ulceration of the epidermis with an infiltrating squamous-cell carcinoma, and invasive anaplastic tumour masses in the dermis. The right ring finger was inflamed, its condition being compatible with mild chronic radiodermatitis, but it showed no cancerous changes. Amputation of the left ring finger was performed. The radioactivity in the ring was confined to the piece inserted in 1946 and measured 700 mrad/hr. Gold seeds containing radon-222 had probably been mixed with gold from other sources and not refined before processing. Another ring worn by the same man and enlarged at the same time showed only 2 mrad-hr. In a second case examined by the authors, Bowen's disease developed in the affected finger and radioactivity of 900 mrad/hr was found in the ring involved. Closer surveillance of industrial gold refining is urged, to prevent further cases of this kind.
THE CHEMICAL ENVIRONMENT
Cr vx with 5 ~o K2Cr207 in 1 Yo sodium lauryl sulphate. One group treated concurrently with an oral suspension of G 35905 S showed a higher incidence of sensitization than the control group. It is suggested in explanation that the drug may promote the reduction of hexavalent to trivalent Cr and thereby encourage protein-binding of the sensitizer. [To underline the importance of such studies of the complexities of chromium sensitization, we may perhaps refer to a report (H. Ebner, Dermatologica 1967, 135, 355) that of 8541 patients treated at a skin clinic during a period of 12 yr, over 9 ~ were found to be sensitized to Cr. The contact eczema of five of these patients was attributed to chromates present in clothing materials.] 1755. Lingering doubts over toluene and xylene Speck, B. & Moeschlin, S. (1968). Die Wirkung von Toluol, Xylol, Chloramphenicol und Thiouracil auf das Knochenmark. Experimentelle autoradiographische Studien mit aHThymidin. Schweiz. med. Wschr. 98, 1684. No depression of bone-marrow function, as measured by the uptake of tritium-labelled thymidine, and no decrease in the numbers of peripheral blood cells or variation in the differential leucocyte picture could be detected in rabbits after daily subcutaneous injections of toluene (I) or xylene (II), in doses of 300 mg/kg for 6 wk or 700 mg/kg for up to 9 wk. Neither I nor II increased the myelotoxic effect of concurrently administered busulphan (10 mg/kg/day for 2 wk), although one would anticipate that when busulphan is given with individual compounds in this way, any potentiation of its myelotoxicity would be readily detectable. The conclusion drawn from these findings is that the aplastic anaemia sometimes observed after long exposure to I or II is attributable to their contamination with benzene rather than to the methylated derivatives themselves. However, in parallel experiments, the authors failed to demonstrate the expected interference with DNA synthesis in the bone marrow by prolonged daily administration of chloramphenicol (500--750 mg/kg/day) or thiouracil (250-400 mg/kg/day), two recognized inducers of human agranulocytosis. It must also be remembered that a wide variation is found in the sensitivity of haemopoietic systems in different species, but it is significant that the same group obtained very different results with benzene in the same species and using the same test procedure, aplastic anaemia being induced by this solvent within 1-9 wk by daily subcutaneous doses of 300 mg/kg/day. In these animals, autoradiography revealed severe inhibition of DNA synthesis in the bone marrow (Cited in F.C.T. 1967, 5, 728). [In view of the ready absorption of toluene through the skin (Cited in F.C.T. 1968, 6, 546), it is encouraging to learn that, at least in the pure form, it may present less of a hazard than is sometimes supposed, but restraint must obviously be exercised in interpreting these findings in terms of the probable effects in man.] 1756. Appraisal of isocyanate workers Bruckner, H. C., Avery, S. B., Stetson, D. M., Dodson, V. N. & Ronayne, J. J. (1968). Clinical and immunologic appraisal of workers exposed to diisocyanates. Archs envir. Hlth 16, 619. It still remains to be established whether the pulmonary response to isocyanates is allergic in nature. Evidence so far has suggested that such a mechanism may operate in some cases (Cited in F.C.T. 1966, 4, 542). To throw further light on this, 44 employees of a company involved with isocyanates
THE CHEMICAL ENVIRONMENT
273
were examined clinically and immunologically and their working environment was assessed. Of these workers, 26 had experienced multiple exposure to isocyanates over periods of up to 11 yr. The remaining 18, who had never worked with isocyanates, served as the control group. The exposed workers were divided into three groups based on isocyanate exposure and the type of response experienced, namely 'minimal' reactors, 'overdose' responders and 'sensitized' reactors. Minimal responders were those who developed some symptoms of mucous-membrane irritation in the eye, mouth and throat, but experienced no bronchial disturbance and had no previous history of allergy. Overdose responders were exposed to higher concentrations and, in addition to mucous-membrane irritation, developed bronchial symptoms and headaches, but they rarely possessed any previous history of allergic disorders. Four of the five members of the exposed sensitized group had a history of allergy. Eye, nose and bronchial reactions, including audible wheezing, rapidly followed test exposure to minute airborne concentrations of isocyanates. No headaches were reported, but repetitive overdose responses were experienced prior to the development of an asthmatic reaction. When signs of sensitization initially developed, after periods of repetitive exposure ranging from 2 months to 5 yr, there was a latent period of up to I-6 hr between exposure and the appearance of asthmatic symptoms, but as the number of exposures increased the exposure-response interval shortened and marked bronchospastic symptoms appeared within seconds of exposure. It is concluded that the asthmatic syndrome occurring in some isocyanate workers is secondary either to a pharmacological overdose or to a hypersensitivity mechanism, with both mechanisms sometimes operating, especially if exposure to high concentrations occurs. 1757. Another matrimonial hazard?
Gerwig, T. & Winer, M. N. (1968). Radioactive jewelry as cause of cutaneous tumour. J. Am. med. Ass. 205, 595.
Radiodermatitis caused by the wearing of a radioactive gold wedding ring has already been reported (Simon & Harley, J. Am. reed. Ass. 1967, 200, 254). The authors cited above have now described a case of skin cancer due to the same cause. A 50-yr-old man complained of a lesion on his left ring finger. He had worn a particular ring on this finger for 10 yr, following its enlargement by a local jeweller in 1946, but then pruritis and discomfort led him to transfer it to his right hand. After a further 8 yr, similar symptoms developed in his right ring finger and in 1964 he stopped wearing the ring altogether. Biopsy of a nodule on the left ring finger showed ulceration of the epidermis with an infiltrating squamous-cell carcinoma, and invasive anaplastic tumour masses in the dermis. The right ring finger was inflamed, its condition being compatible with mild chronic radiodermatitis, but it showed no cancerous changes. Amputation of the left ring finger was performed. The radioactivity in the ring was confined to the piece inserted in 1946 and measured 700 mrad/hr. Gold seeds containing radon-222 had probably been mixed with gold from other sources and not refined before processing. Another ring worn by the same man and enlarged at the same time showed only 2 mrad-hr. In a second case examined by the authors, Bowen's disease developed in the affected finger and radioactivity of 900 mrad/hr was found in the ring involved. Closer surveillance of industrial gold refining is urged, to prevent further cases of this kind.