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TOXICOLOGY 879 The toxicity to the chick embryo of the pesticides methyl parathion, guthion, lindane, demeton, heptachlor epoxide, endrin, dieldrin, DDT, disyston, parathion, malathion and EPN correlated well with the corresponding acute oral toxicities in the rat (Marliac et aL cited above). The ratios of chick to rat toxicity varied from 0-5 to 2.0. In some instances, however, the chick embryo was much more sensitive than the rat; for example carbaryl and diazinon were found to be 30 and 300 times more toxic, respectively, to the chick embryo than to the rat. Another paper delivered at this Meeting, described the toxic effects induced by inocula- tion of EPN or systox into duck eggs* (Khera et al. cited above; Fd. Cosmet. Toxicol. 1965, 3, 581). Ducklings which hatched from eggs inoculated on day 13 of incubation with 10 ~g/egg of either pesticide exhibited partial to complete loss of voluntary control of one or both hind legs. Although this toxic effect disappeared 5 days post-hatching, growth retardation continued. Inhibition of the acetylcholinesterase activity of motor end-plates was detected from 20 days of age until the day of hatching. Degenerative changes in skeletal muscles alternating with areas of marked regenerative activity were seen on histological examination. [Obviously, much remains to be done before we can fully appreciate the extent to which the chick embryo technique is going to contribute to the established methods of assessing toxicity. The above results clearly show that the toxic response in the chick embryo and various mammalian species for a variety of compounds is much closer than some people would care to think.] TOXICOLOGY 919. Pharmacological effects of dimethylsulphoxide Auclair, M. & Thevenot, R. (1964). Toxicologic et pharmacologic d'un solvant organique le dim6thylsulfoxyde. C.r. S~anc. Soc. Biol. 158, 1857. Hardly an issue of the Journal appears nowadays without some mention of dimethyl- sulphoxide (I) whose low order of toxicity has been repeatedly demonstrated by many workers. The present authors have found that the activity of isolated rat duodenum and guinea-pig ileum was only affected to any extent at relatively high concentrations of I (0.5-5 parts per 100). In addition, the effectiveness of papaverine and promethazine is stated to be unaffected by administering them in I (concentration not stated), corroborating previous work with other drugs (Cited in F.C.T. 1965, 3, 670). In contrast to these results, I induced intense pharmacological reactions when injected intravenously into cats. Precipitous hypotension followed by irreversible cardiac arrest was produced by 0.5 ml/kg. Half this dose only caused slight temporary hypotension, although the heart was arrested, and 0.1 ml/kg was almost ineffective in this respect. Kidney volume was decreased due to vasoconstriction, the amplitude of respiration increased and the tone and amplitude of duodenal contractions also increased. The severity of these reactions in cats together with the possibility that I may be hepato- toxic in dogs (Cited in F.C.T. 1965, 3, 540) suggest that caution should be exercised in the use of I as a vehicle in animal experiments. 920. Therapeutic value of dimethylsulphoxide Journal of the American Medical Association--Editorial (1965). The story of DMSO. ibid 192, 320. Rosenbaum, E. E., Herschler, R. J. & Jacob, S. W. (1965). Dimethyl sulfoxide in musculo- skeletal disorders. J. Am. reed. Ass. 192, 309. *The full paper on this work was published in this Journal (1965, 3, 581).

919. Pharmacological effects of dimethylsulphoxide: Auclair, M. & Thevenot, R. (1964). Toxicologie et pharmacologie d'un solvant organique le diméthylsulfoxyde. C.r. Séanc. Soc

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TOXICOLOGY 879

The toxicity to the chick embryo of the pesticides methyl parathion, guthion, lindane, demeton, heptachlor epoxide, endrin, dieldrin, DDT, disyston, parathion, malathion and EPN correlated well with the corresponding acute oral toxicities in the rat (Marliac et aL cited above). The ratios of chick to rat toxicity varied from 0-5 to 2.0. In some instances, however, the chick embryo was much more sensitive than the rat; for example carbaryl and diazinon were found to be 30 and 300 times more toxic, respectively, to the chick embryo than to the rat.

Another paper delivered at this Meeting, described the toxic effects induced by inocula- tion of EPN or systox into duck eggs* (Khera et al. cited above; Fd. Cosmet. Toxicol. 1965, 3, 581). Ducklings which hatched from eggs inoculated on day 13 of incubation with 10 ~g/egg of either pesticide exhibited partial to complete loss of voluntary control of one or both hind legs. Although this toxic effect disappeared 5 days post-hatching, growth retardation continued. Inhibition of the acetylcholinesterase activity of motor end-plates was detected from 20 days of age until the day of hatching. Degenerative changes in skeletal muscles alternating with areas of marked regenerative activity were seen on histological examination.

[Obviously, much remains to be done before we can fully appreciate the extent to which the chick embryo technique is going to contribute to the established methods of assessing toxicity. The above results clearly show that the toxic response in the chick embryo and various mammalian species for a variety of compounds is much closer than some people would care to think.]

TOXICOLOGY

919. Pharmacological effects of dimethylsulphoxide Auclair, M. & Thevenot, R. (1964). Toxicologic et pharmacologic d'un solvant organique le dim6thylsulfoxyde. C.r. S~anc. Soc. Biol. 158, 1857.

Hardly an issue of the Journal appears nowadays without some mention of dimethyl- sulphoxide (I) whose low order of toxicity has been repeatedly demonstrated by many workers. The present authors have found that the activity of isolated rat duodenum and guinea-pig ileum was only affected to any extent at relatively high concentrations of I (0.5-5 parts per 100). In addition, the effectiveness of papaverine and promethazine is stated to be unaffected by administering them in I (concentration not stated), corroborating previous work with other drugs (Cited in F.C.T. 1965, 3, 670).

In contrast to these results, I induced intense pharmacological reactions when injected intravenously into cats. Precipitous hypotension followed by irreversible cardiac arrest was produced by 0.5 ml/kg. Half this dose only caused slight temporary hypotension, although the heart was arrested, and 0.1 ml/kg was almost ineffective in this respect. Kidney volume was decreased due to vasoconstriction, the amplitude of respiration increased and the tone and amplitude of duodenal contractions also increased.

The severity of these reactions in cats together with the possibility that I may be hepato- toxic in dogs (Cited in F.C.T. 1965, 3, 540) suggest that caution should be exercised in the use of I as a vehicle in animal experiments.

920. Therapeutic value of dimethylsulphoxide Journal of the American Medical Association--Editorial (1965). The story of DMSO. ibid 192, 320. Rosenbaum, E. E., Herschler, R. J. & Jacob, S. W. (1965). Dimethyl sulfoxide in musculo- skeletal disorders. J. Am. reed. Ass. 192, 309. *The full paper on this work was published in this Journal (1965, 3, 581).