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1630. Change the route and change the toxicity
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FEED ADDITIVES
present paper reports an extension of this work to a number of materials, whose acute toxicity was in all cases enhanced by administration in combination with PB. Infant mice were given graded subcutaneous doses of Freon 112 (CC12F.CC12F; I), Freon 113 (CC12F.CCIF2; II) or griseofulvin (GF) on days 1, 7, 14 and 21 after birth or a single dose of benzo[a]pyrene (BP). Each material was given alone and combined with PB, and the toxicity was expressed in terms of mortality at 7, 14 or 21 days. Apart from mice given high initial doses (0.5 or 5 mg) of GF, the 21-day mortality from the test materials or solvent alone ranged from 2 to 13 %. When combined with PB, mortality from BP rose to "35 ~o, from II to 46 %, from I to 55 ~ and from GF (0.25 mg) to 81 ~o. PB raised the mortality from GF (0.5 mg) from 42 to 100%. The increased mortality following combination with PB was associated with an anomalous weight-gain (not attributable to any preferential survival of male animals), which was usually pronounced by 21 days. The design of this experiment does not permit any firm conclusion to be drawn on whether this enhanced toxicity is a synergistic or a simple additive effect, but it does indicate a potential hazard from exposure to PB. 1630. Change the route and change the toxicity Natoff, I. L. (1967). Influence of the route of administration on the toxicity of some cholinesterase inhibitors. J. Pharm. Pharmac. 19, 612. The route by which organophosphorus and carbamate cholinesterase inhibitors reach the liver may influence the toxicity of these compounds. The present author makes a distinction between the intravenous and subcutaneous ('peripheral') routes--whereby the compound enters the peripheral venous circulation directly and only about a quarter of the dose is transported to the liver on its first passage through the body--and the oral and intraperitoneal ('hepatic') routes, whereby entry into the peripheral venous circulation is gained primarily through the hepatic portal system. In other words, more material is likely to be detoxified before it is re-circulated if it has been given by a 'hepatic' than by a 'peripheral' route. The acute LDsos of several organophosphorus pesticides were determined by these four routes in mice. Ciodrin, phosdrin, paraoxon and the carbamates physostigmine and neostigrnine were more toxic by the 'peripheral' than by the 'hepatic' routes, indicating the importance of the liver in their detoxication. With some other compounds, however, namely azodrin, bidrin (which is N-demethylated in vivo to yield azodrin) and chlorfenvinphos, toxicity was not influenced by the availability of the compound for metabolism by the liver. Other findings indicated that, in general, absorption of these compounds from the intestine or subcutaneous site was poor.
FEED ADDITIVES 1631. Qacs, turkeys and the FDA Mayeda, B. (1968). The toxic effects in turkey poults of a quaternary ammonium compound in drinking water at 150 and 200 ppm. Avian Dis. 12, 67. This paper describes tests on a quaternary ammonium (QA) formulation sold for use as a disinfectant at levels of I00 ppm in drinking water for poultry. The formulation contained four QA salts based on dimethyl 3,4-dichlorobenzylammonium chloride, namely the lauryl
FEED ADDITIVES
present paper reports an extension of this work to a number of materials, whose acute toxicity was in all cases enhanced by administration in combination with PB. Infant mice were given graded subcutaneous doses of Freon 112 (CC12F.CC12F; I), Freon 113 (CC12F.CCIF2; II) or griseofulvin (GF) on days 1, 7, 14 and 21 after birth or a single dose of benzo[a]pyrene (BP). Each material was given alone and combined with PB, and the toxicity was expressed in terms of mortality at 7, 14 or 21 days. Apart from mice given high initial doses (0.5 or 5 mg) of GF, the 21-day mortality from the test materials or solvent alone ranged from 2 to 13 %. When combined with PB, mortality from BP rose to "35 ~o, from II to 46 %, from I to 55 ~ and from GF (0.25 mg) to 81 ~o. PB raised the mortality from GF (0.5 mg) from 42 to 100%. The increased mortality following combination with PB was associated with an anomalous weight-gain (not attributable to any preferential survival of male animals), which was usually pronounced by 21 days. The design of this experiment does not permit any firm conclusion to be drawn on whether this enhanced toxicity is a synergistic or a simple additive effect, but it does indicate a potential hazard from exposure to PB. 1630. Change the route and change the toxicity Natoff, I. L. (1967). Influence of the route of administration on the toxicity of some cholinesterase inhibitors. J. Pharm. Pharmac. 19, 612. The route by which organophosphorus and carbamate cholinesterase inhibitors reach the liver may influence the toxicity of these compounds. The present author makes a distinction between the intravenous and subcutaneous ('peripheral') routes--whereby the compound enters the peripheral venous circulation directly and only about a quarter of the dose is transported to the liver on its first passage through the body--and the oral and intraperitoneal ('hepatic') routes, whereby entry into the peripheral venous circulation is gained primarily through the hepatic portal system. In other words, more material is likely to be detoxified before it is re-circulated if it has been given by a 'hepatic' than by a 'peripheral' route. The acute LDsos of several organophosphorus pesticides were determined by these four routes in mice. Ciodrin, phosdrin, paraoxon and the carbamates physostigmine and neostigrnine were more toxic by the 'peripheral' than by the 'hepatic' routes, indicating the importance of the liver in their detoxication. With some other compounds, however, namely azodrin, bidrin (which is N-demethylated in vivo to yield azodrin) and chlorfenvinphos, toxicity was not influenced by the availability of the compound for metabolism by the liver. Other findings indicated that, in general, absorption of these compounds from the intestine or subcutaneous site was poor.
FEED ADDITIVES 1631. Qacs, turkeys and the FDA Mayeda, B. (1968). The toxic effects in turkey poults of a quaternary ammonium compound in drinking water at 150 and 200 ppm. Avian Dis. 12, 67. This paper describes tests on a quaternary ammonium (QA) formulation sold for use as a disinfectant at levels of I00 ppm in drinking water for poultry. The formulation contained four QA salts based on dimethyl 3,4-dichlorobenzylammonium chloride, namely the lauryl