- Email: [email protected]
1988. Industrial chemicals—inhalation toxicity data
THE CHEMICALENVIRONMENT
467
1987. Impotence: A new pesticide threat? Espir, M. L. E., Hall, J. W., Shirreffs, J. G. & Stevens, D. L. (1970). Impotence in farm workers using toxic chemicals. Br. reed. J. 1, 423. Peck, A. W. (1970). Impotence in farm workers. Br. reed. J. 1, 690. Espir et al. (cited above) present circumstantial evidence incriminating toxic agricultural chemicals as the cause of impotence in four members of a group of five farmworkers. All of the affected workers had previously achieved normal erection and all responded favourably to androgen therapy with methyltestosterone after contact with the chemicals had been stopped. The insecticides and herbicides used by these men were organophosphorus compounds, substituted phenols, bipyridyls, organochlorines, substituted phenoxy compounds, triazines, carbamates, dithiocarbamates, ureas and uracils. Impotence was the only toxic symptom seen in these workers and the most likely cause was considered to be the pesticide exposure. There was no indication as to which of the pesticides, acting singly or in concert, may have been responsible. The authors, however, cite a report in Medical News-Tribune (19 December 1969, p. 21) linking exposure to Metasystox 55 (an organophosphate), Gesatop (a sym-triazine derivative) and Tecane (a trichloroacetic acid formulation) with the occurrence of impotence, nausea and indigestion in a single agricultural worker. Peck (cited above) attributes this unusual phenomenon to an androgen deficiency resulting from enhanced hydroxylation of testosterone in liver microsomes induced by the organochlorine pesticides, which are known to be potent inducers of microsomal enzymes. He points out, however, that the organophosphorus pesticide, chlorthion, inhibits testosterone hydroxylation, so the net effect of the pesticides on the farmworkers' liver microsomes may be governed by the summation of the individual effects, which may not necessarily work in the same direction. [This is probably the first report of reversible impotence in agricultural workers exposed to pesticides. Although not conclusively proven, the evidence appears strong enough to call for an immediate enquiry into the potential hazard of pesticides to the vital function of reproduction in man and animals. It cannot be argued that the occupational pesticide exposure encountered was excessively high, otherwise other symptoms more characteristic of pesticide toxicity would have been apparent.]
THE CHEMICAL ENVIRONMENT 1988. Industrial chemicals--inhalation toxicity data Gage, J. C. (1970). The subacute inhalation toxicity of 109 industrial chemicals. Br. J. ind. Med. 27, 1. The majority of serious occupational diseases arising from exposure to chemicals are caused by the effect of such chemicals on, or their absorption through, the respiratory tract. The present investigations were carried out to provide a basis for the establishment of safety precautions to minimize the hazards to workers exposed to various industrial chemicals. The inhalation toxicity of 109 substances was studied by exposing rats to known concentrations in air for periods of up to 6 hr on 5 days/wk for up to 4 wk, and brief details of the results obtained are given in this paper. The materials covered are too numerous to
468
THE CHEMICAL ENVIRONMENT
list but include hydrocarbons, alcohols, ethers, aldehydes and ketones, acids, esters, chlorinated hydrocarbons, amines, nitriles, some heterocyclic compounds and peroxy, organophosphorus, silicon and sulphur compounds. The toxic properties of these substances are reviewed in relation to the effects of similar compounds on animals and man. Finally, a provisional maximum acceptable concentration in the working atmosphere is suggested for each compound. 1989. Neurological disorders from manganese Tanaka, S. & Lieben, J. (1969). Manganese poisoning and exposure in Pennsylvania. Archs envir. Hlth 19, 674. Manganism is a rare neurological disease except in areas where manganese ore is mined (Rodier, Br. J. ind. Med. 1955, 12, 21). Involvement of organs other than the nervous system is infrequent although a high incidence of pneumonia has been observed among manganese miners (Von Oettingen, Physiol. Ret,. 1935, 15, 175). The authors cited above carried out a survey of manganese exposure in 75 Pennsylvanian industrial plants. Of 117 workers from plants with excessive exposure (above the US threshold limit (ceiling) value of 5 mg/m 3 air), seven were found to show definite signs of manganese poisoning and the detailed case histories of three of these are described. Attempts to find a correlation between individual urinary levels of manganese and clinical findings of manganism were not successful. This was probably because urinary manganese concentrations reflected the levels of recent absorption while the observed signs and symptoms were the result of past exposure over months or even years. A reasonable correlation was established, however, when mean urinary levels of manganese for each group were plotted against mean atmospheric manganese concentrations. The administration of calcium disodium edetate in the early stages of manganese poisoning has proved successful in removing manganese from the body and reversing adverse effects (Whitlock et al. Am. ind. Hyg. Ass. J. 1966, 27, 454) but this procedure is ineffective in the treatment of patients with established neurological changes. 1990. Light on the action of acetylsalicylates Ramsay, A. G., Elliott, H. C. & Haynes, A. M. (1969). The effect of methyl acetylsalicylate on renal tubular ionic reabsorption. Proc. Soc. exp. Biol. Med. 132, 307. These authors have studied in anaesthetized dogs the extent to which the ionic clearance rate of the kidneys is affected by the addition of methyl acetylsalicylate (MA) to a mannitol and inulin intravenous infusion in an amount to provide a total of 120 mg MA administered at a rate of I mg/min. This MA significantly decreased the urinary excretion rate of sodium, chloride, bicarbonate, calcium and magnesium ions, although it increased the filtered load of these ions. It was therefore concluded that MA increased the tubular reabsorption of the ions. One mechanism leading to increased reabsorption appeared to be a decrease in renal plasma flow (RPF), but even in the absence of a falling RPF it was possible to observe increased ionic reabsorption. Such observations indicate that MA may exert a direct action upon tubular transport mechanisms in the kidney, for example by attaching to a carrier protein and increasing the number of carrier sites, or by increasing the production of metabolic energy required for active transport. Alternatively, it may increase the permeability of the luminal membrane of the cell. Whatever the mechanism, a chemical specificity is evident, attributable to the position of the oxygen atoms in the substituent group ortho
467
1987. Impotence: A new pesticide threat? Espir, M. L. E., Hall, J. W., Shirreffs, J. G. & Stevens, D. L. (1970). Impotence in farm workers using toxic chemicals. Br. reed. J. 1, 423. Peck, A. W. (1970). Impotence in farm workers. Br. reed. J. 1, 690. Espir et al. (cited above) present circumstantial evidence incriminating toxic agricultural chemicals as the cause of impotence in four members of a group of five farmworkers. All of the affected workers had previously achieved normal erection and all responded favourably to androgen therapy with methyltestosterone after contact with the chemicals had been stopped. The insecticides and herbicides used by these men were organophosphorus compounds, substituted phenols, bipyridyls, organochlorines, substituted phenoxy compounds, triazines, carbamates, dithiocarbamates, ureas and uracils. Impotence was the only toxic symptom seen in these workers and the most likely cause was considered to be the pesticide exposure. There was no indication as to which of the pesticides, acting singly or in concert, may have been responsible. The authors, however, cite a report in Medical News-Tribune (19 December 1969, p. 21) linking exposure to Metasystox 55 (an organophosphate), Gesatop (a sym-triazine derivative) and Tecane (a trichloroacetic acid formulation) with the occurrence of impotence, nausea and indigestion in a single agricultural worker. Peck (cited above) attributes this unusual phenomenon to an androgen deficiency resulting from enhanced hydroxylation of testosterone in liver microsomes induced by the organochlorine pesticides, which are known to be potent inducers of microsomal enzymes. He points out, however, that the organophosphorus pesticide, chlorthion, inhibits testosterone hydroxylation, so the net effect of the pesticides on the farmworkers' liver microsomes may be governed by the summation of the individual effects, which may not necessarily work in the same direction. [This is probably the first report of reversible impotence in agricultural workers exposed to pesticides. Although not conclusively proven, the evidence appears strong enough to call for an immediate enquiry into the potential hazard of pesticides to the vital function of reproduction in man and animals. It cannot be argued that the occupational pesticide exposure encountered was excessively high, otherwise other symptoms more characteristic of pesticide toxicity would have been apparent.]
THE CHEMICAL ENVIRONMENT 1988. Industrial chemicals--inhalation toxicity data Gage, J. C. (1970). The subacute inhalation toxicity of 109 industrial chemicals. Br. J. ind. Med. 27, 1. The majority of serious occupational diseases arising from exposure to chemicals are caused by the effect of such chemicals on, or their absorption through, the respiratory tract. The present investigations were carried out to provide a basis for the establishment of safety precautions to minimize the hazards to workers exposed to various industrial chemicals. The inhalation toxicity of 109 substances was studied by exposing rats to known concentrations in air for periods of up to 6 hr on 5 days/wk for up to 4 wk, and brief details of the results obtained are given in this paper. The materials covered are too numerous to
468
THE CHEMICAL ENVIRONMENT
list but include hydrocarbons, alcohols, ethers, aldehydes and ketones, acids, esters, chlorinated hydrocarbons, amines, nitriles, some heterocyclic compounds and peroxy, organophosphorus, silicon and sulphur compounds. The toxic properties of these substances are reviewed in relation to the effects of similar compounds on animals and man. Finally, a provisional maximum acceptable concentration in the working atmosphere is suggested for each compound. 1989. Neurological disorders from manganese Tanaka, S. & Lieben, J. (1969). Manganese poisoning and exposure in Pennsylvania. Archs envir. Hlth 19, 674. Manganism is a rare neurological disease except in areas where manganese ore is mined (Rodier, Br. J. ind. Med. 1955, 12, 21). Involvement of organs other than the nervous system is infrequent although a high incidence of pneumonia has been observed among manganese miners (Von Oettingen, Physiol. Ret,. 1935, 15, 175). The authors cited above carried out a survey of manganese exposure in 75 Pennsylvanian industrial plants. Of 117 workers from plants with excessive exposure (above the US threshold limit (ceiling) value of 5 mg/m 3 air), seven were found to show definite signs of manganese poisoning and the detailed case histories of three of these are described. Attempts to find a correlation between individual urinary levels of manganese and clinical findings of manganism were not successful. This was probably because urinary manganese concentrations reflected the levels of recent absorption while the observed signs and symptoms were the result of past exposure over months or even years. A reasonable correlation was established, however, when mean urinary levels of manganese for each group were plotted against mean atmospheric manganese concentrations. The administration of calcium disodium edetate in the early stages of manganese poisoning has proved successful in removing manganese from the body and reversing adverse effects (Whitlock et al. Am. ind. Hyg. Ass. J. 1966, 27, 454) but this procedure is ineffective in the treatment of patients with established neurological changes. 1990. Light on the action of acetylsalicylates Ramsay, A. G., Elliott, H. C. & Haynes, A. M. (1969). The effect of methyl acetylsalicylate on renal tubular ionic reabsorption. Proc. Soc. exp. Biol. Med. 132, 307. These authors have studied in anaesthetized dogs the extent to which the ionic clearance rate of the kidneys is affected by the addition of methyl acetylsalicylate (MA) to a mannitol and inulin intravenous infusion in an amount to provide a total of 120 mg MA administered at a rate of I mg/min. This MA significantly decreased the urinary excretion rate of sodium, chloride, bicarbonate, calcium and magnesium ions, although it increased the filtered load of these ions. It was therefore concluded that MA increased the tubular reabsorption of the ions. One mechanism leading to increased reabsorption appeared to be a decrease in renal plasma flow (RPF), but even in the absence of a falling RPF it was possible to observe increased ionic reabsorption. Such observations indicate that MA may exert a direct action upon tubular transport mechanisms in the kidney, for example by attaching to a carrier protein and increasing the number of carrier sites, or by increasing the production of metabolic energy required for active transport. Alternatively, it may increase the permeability of the luminal membrane of the cell. Whatever the mechanism, a chemical specificity is evident, attributable to the position of the oxygen atoms in the substituent group ortho