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811. Chlorinated benzenes and disturbances in porphyrin metabolism
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AGRICULTURALCHEMICALS
It was concluded that although pretreatment with I produces an adaptive response which raises the sheep's tolerance to I it is the level of II in the blood that is the important lethal factor involved in poisoning by I.
AGRICULTURAL CHEMICALS 811. Chlorinated benzenes and disturbances in porphyrin metabolism Rimington, C. & Ziegler, G. (1963). Experimental porphyria in rats induced by chlorinated benzenes. Biochem. Pharmac. 12, 1387. Haeger-Aronsen, Birgitta (1964). Experimental disturbance of porphyrin metabolism and of liver catalase activity in guinea pigs and rabbits. Acta pharmac, tox. 21, 105. A widespread outbreak of cutaneous porphyria in Turkey in 1959 was traced to the ingestion of wheat treated with the fungicide hexachlorobenzene (I) and hepatic porphyria was later produced experimentally in rats and rabbits by feeding I (Cited in F.C.T. 1963, 1, 126). According to Rimington & Ziegler (cited above) continued ingestion of mono-, di-, triand tetrachlorobenzene by rats also resulted in an hepatic type of porphyria characterized by greatly increased concentrations of porphyrins and porphyrin-precursors in the liver and excreta. Pentactdorobenzene was without effect. It is of some interest that the urinary elimination was greater when the chlorobenzenes were administered in liquid paraffin or propylene glycol than as suspensions in cellofas. The first sign of intoxication was a rise in the urinary level of coproporphyrin; increases in urinary porphobilinogen and &aminolaevulinic acid occurred later. The most active chlorobenzenes were those with 2 chlorine atoms in a para position to one another [1,4-dichlorobenzene, 1,2,4-trich]orobenzene (II) and 1,2,3,4-tetrachlor0benzene (III)]. These porphyrin disturbances differed from those induced by I in that uroporphyrin excretion was low. Liver glutathione (GSH) was reduced ordy by II. The effect of II on porphyrin metabolism could be largely prevented by concomitant administration of GSH. III caused hair loss due to follicular hyperkeratosis, similar to the skin lesions produced in man by chlorinated benzenes. There were no signs of photosensitivity. The study of Haeger-Aronsen (cited above) which was prompted by species differences in susceptibility to I, compared the changes in porphyrin metabolism and liver catalase (a haemoprotein enzyme) activities in guinea-pigs and rabbits given intubated doses of 0.4-0.9 g I/kg and 1.4-2.8 g I/kg respectively. Guinea-pigs treated with I for several days developed a coarse tremor of the limbs and excreted a slightly increased amount of laevulinic acid in the urine. Rabbits, on the other hand, excreted increased amounts of porphyrins in both urine and faeces. Liver catalase activity was unaffected in both species. 812. New pyrethrin-type insecticides
Masri, M. S., Jones, F. T., Lundin, R. E., Bailey, G. F. & DeEds, F. (1964). Metabolic fate of two chrysanthemumic acid esters: Barthrin and dimethrin. Toxic. appl. Pharmac. 6, 711. Masri, M. S., Hendrickson, A. P., Cox, A. J., Jr. & DeEds, F. (1964). Subacute toxicity of two chrysanthemumic acid esters: Bart~in and dimethrin. Toxic. appl. Pharmac. 6, 716. Chikamoto, T. (1964). The toxicity of chrysanthemyl-, allethronyl- and piperonyl piperonylutes and the higher homologues. Agric. biol. Chem. 28, 633. Two new insecticides, chrysanthemumic acid esters of 6-chloropiperonyl alcohol (barthrin; I) and 2,4-dimethylbenzyl alcohol (dimethrin; II) are reported to be much less toxic towards mammals than pyrethrin and allettwin. Their use against house-flies resistant to chlorinated hydrocarbons and their addition to animal food to render the faeces free from certain pests are among the many uses claimed for these two compounds.
AGRICULTURALCHEMICALS
It was concluded that although pretreatment with I produces an adaptive response which raises the sheep's tolerance to I it is the level of II in the blood that is the important lethal factor involved in poisoning by I.
AGRICULTURAL CHEMICALS 811. Chlorinated benzenes and disturbances in porphyrin metabolism Rimington, C. & Ziegler, G. (1963). Experimental porphyria in rats induced by chlorinated benzenes. Biochem. Pharmac. 12, 1387. Haeger-Aronsen, Birgitta (1964). Experimental disturbance of porphyrin metabolism and of liver catalase activity in guinea pigs and rabbits. Acta pharmac, tox. 21, 105. A widespread outbreak of cutaneous porphyria in Turkey in 1959 was traced to the ingestion of wheat treated with the fungicide hexachlorobenzene (I) and hepatic porphyria was later produced experimentally in rats and rabbits by feeding I (Cited in F.C.T. 1963, 1, 126). According to Rimington & Ziegler (cited above) continued ingestion of mono-, di-, triand tetrachlorobenzene by rats also resulted in an hepatic type of porphyria characterized by greatly increased concentrations of porphyrins and porphyrin-precursors in the liver and excreta. Pentactdorobenzene was without effect. It is of some interest that the urinary elimination was greater when the chlorobenzenes were administered in liquid paraffin or propylene glycol than as suspensions in cellofas. The first sign of intoxication was a rise in the urinary level of coproporphyrin; increases in urinary porphobilinogen and &aminolaevulinic acid occurred later. The most active chlorobenzenes were those with 2 chlorine atoms in a para position to one another [1,4-dichlorobenzene, 1,2,4-trich]orobenzene (II) and 1,2,3,4-tetrachlor0benzene (III)]. These porphyrin disturbances differed from those induced by I in that uroporphyrin excretion was low. Liver glutathione (GSH) was reduced ordy by II. The effect of II on porphyrin metabolism could be largely prevented by concomitant administration of GSH. III caused hair loss due to follicular hyperkeratosis, similar to the skin lesions produced in man by chlorinated benzenes. There were no signs of photosensitivity. The study of Haeger-Aronsen (cited above) which was prompted by species differences in susceptibility to I, compared the changes in porphyrin metabolism and liver catalase (a haemoprotein enzyme) activities in guinea-pigs and rabbits given intubated doses of 0.4-0.9 g I/kg and 1.4-2.8 g I/kg respectively. Guinea-pigs treated with I for several days developed a coarse tremor of the limbs and excreted a slightly increased amount of laevulinic acid in the urine. Rabbits, on the other hand, excreted increased amounts of porphyrins in both urine and faeces. Liver catalase activity was unaffected in both species. 812. New pyrethrin-type insecticides
Masri, M. S., Jones, F. T., Lundin, R. E., Bailey, G. F. & DeEds, F. (1964). Metabolic fate of two chrysanthemumic acid esters: Barthrin and dimethrin. Toxic. appl. Pharmac. 6, 711. Masri, M. S., Hendrickson, A. P., Cox, A. J., Jr. & DeEds, F. (1964). Subacute toxicity of two chrysanthemumic acid esters: Bart~in and dimethrin. Toxic. appl. Pharmac. 6, 716. Chikamoto, T. (1964). The toxicity of chrysanthemyl-, allethronyl- and piperonyl piperonylutes and the higher homologues. Agric. biol. Chem. 28, 633. Two new insecticides, chrysanthemumic acid esters of 6-chloropiperonyl alcohol (barthrin; I) and 2,4-dimethylbenzyl alcohol (dimethrin; II) are reported to be much less toxic towards mammals than pyrethrin and allettwin. Their use against house-flies resistant to chlorinated hydrocarbons and their addition to animal food to render the faeces free from certain pests are among the many uses claimed for these two compounds.