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2253. Phthalate plasticizers and PVC blood packs
910
PROCESSING AND PACKAGING CONTAMINANTS
chez le rat au cours de l'intoxication exp6rimentale par les herbicides d6riv6s du dinitroph6nol: DNBP (dinos~be) et DNPP (dinoprope). Eur. J. ToxicoL 4, 9. The above study was carried out to investigate the hepatotoxicity of the herbicides, 2-isobutyl- and 2-isopropyl-4,6-dinitrophenol (DNBP and DNPP, respectively). Each compound was given to rats by intubation in a single dose of 60 mg/kg, in a daily dose of 20 or 25 mg/kg until death and in a dose of 10 mg/kg/day for 32 days. The doses of 25 mg/kg proved fatal after a single intubation, while 20 mg DNPP/kg/day killed all the rats within 2 days and 20 mg DNBP/kg/day killed 60% of those treated within 3 days and the rest within 10 days. Both DNBP and DNPP produced a mild methaemoglobinaemia following single or repeated doses. This effect was most pronounced in the 32-day study with DNPP, with a maximum methaemoglobin level in the blood of 12-13% of the total haemoglobin. The methaemoglobinaemia was accompanied by an increased excretion of coproporphyrins in the urine. With either herbicide, a dose of 10 mg/kg/day caused a significant increase in the haemoglobin and erythrocyte levels in the blood. In the 32-day study, DNBP and DNPP had an effect on liver function, as evidenced by a significant increase in urinary urobilinogen. Histological examination of the rat livers subsequently revealed some characteristic signs of liver damage (fatty liver, a reduction in glycogen content, congestion and changes suggesting stimulation of the reticulo-endothelial system), but no specific lesions were found. The author concludes that the jaun.dice resulting from the repeated administration of DNBP or DNPP results from the action of these compounds on the haemoglobin rather than from a direct hepatotoxic effect.
PROCESSING AND P A C K A G I N G C O N T A M I N A N T S
2253. Phthalate plasticizers and PVC blood packs Marcel, Y. L. & Noel, S. P. (1970). Contamination of blood stored in plastic packs. Lancet i, 35. Jaeger, R. J. & Rubin, R. J. (1970). Plasticizers from plastic devices: Extraction, metabolism, and accumulation by biological systems. Science, N.Y. 170, 460. During the past year it has become apparent that significant quantities of di-(2-ethylhexyl) phthalate (DEHP) can be detected in blood that has been stored in PVC packs. Early in 1970, it was reported (first paper cited above) that a phthalate plasticizer in concentrations of 0, 4, 7, 11-5 and 11.5 mg/100 ml plasma was demonstrated by thin-layer chromatography in blood stored for 0, 4, 8, 15 and 21 days, respectively, in plastics transfusion packs at 4°C. At this stage the plasticizer was thought to be dihexyl phthalate (DHP) but it was rapidly pointed out by the manufacturers (Geslar & Kartinos, Lancet 1970, i, 1227) that it was, in fact, DEHP, which is difficult to distinguish from DHP by the infrared spectrophotometric and gas-liquid chromatographic methods used in this case for its identification. Marcel & Noel (Chem. Phys. Lipids 1970, 4, 418) subsequently agreed with this identification. The reported LD5o values for DEHP in rodents range from 14 to 128 g/kg and, on the basis of the lower figure, Geslar & Kartinos (loc. cit.) calculated that in a complete exchange transfusion using blood contaminated at a level of 11.5 mg/100 ml, a 70-kg adult would receive a quantity of D E H P some 2500 times less than the LDso.
PROCESSING AND PACKAGING CONTAMINANTS
chez le rat au cours de l'intoxication exp6rimentale par les herbicides d6riv6s du dinitroph6nol: DNBP (dinos~be) et DNPP (dinoprope). Eur. J. ToxicoL 4, 9. The above study was carried out to investigate the hepatotoxicity of the herbicides, 2-isobutyl- and 2-isopropyl-4,6-dinitrophenol (DNBP and DNPP, respectively). Each compound was given to rats by intubation in a single dose of 60 mg/kg, in a daily dose of 20 or 25 mg/kg until death and in a dose of 10 mg/kg/day for 32 days. The doses of 25 mg/kg proved fatal after a single intubation, while 20 mg DNPP/kg/day killed all the rats within 2 days and 20 mg DNBP/kg/day killed 60% of those treated within 3 days and the rest within 10 days. Both DNBP and DNPP produced a mild methaemoglobinaemia following single or repeated doses. This effect was most pronounced in the 32-day study with DNPP, with a maximum methaemoglobin level in the blood of 12-13% of the total haemoglobin. The methaemoglobinaemia was accompanied by an increased excretion of coproporphyrins in the urine. With either herbicide, a dose of 10 mg/kg/day caused a significant increase in the haemoglobin and erythrocyte levels in the blood. In the 32-day study, DNBP and DNPP had an effect on liver function, as evidenced by a significant increase in urinary urobilinogen. Histological examination of the rat livers subsequently revealed some characteristic signs of liver damage (fatty liver, a reduction in glycogen content, congestion and changes suggesting stimulation of the reticulo-endothelial system), but no specific lesions were found. The author concludes that the jaun.dice resulting from the repeated administration of DNBP or DNPP results from the action of these compounds on the haemoglobin rather than from a direct hepatotoxic effect.
PROCESSING AND P A C K A G I N G C O N T A M I N A N T S
2253. Phthalate plasticizers and PVC blood packs Marcel, Y. L. & Noel, S. P. (1970). Contamination of blood stored in plastic packs. Lancet i, 35. Jaeger, R. J. & Rubin, R. J. (1970). Plasticizers from plastic devices: Extraction, metabolism, and accumulation by biological systems. Science, N.Y. 170, 460. During the past year it has become apparent that significant quantities of di-(2-ethylhexyl) phthalate (DEHP) can be detected in blood that has been stored in PVC packs. Early in 1970, it was reported (first paper cited above) that a phthalate plasticizer in concentrations of 0, 4, 7, 11-5 and 11.5 mg/100 ml plasma was demonstrated by thin-layer chromatography in blood stored for 0, 4, 8, 15 and 21 days, respectively, in plastics transfusion packs at 4°C. At this stage the plasticizer was thought to be dihexyl phthalate (DHP) but it was rapidly pointed out by the manufacturers (Geslar & Kartinos, Lancet 1970, i, 1227) that it was, in fact, DEHP, which is difficult to distinguish from DHP by the infrared spectrophotometric and gas-liquid chromatographic methods used in this case for its identification. Marcel & Noel (Chem. Phys. Lipids 1970, 4, 418) subsequently agreed with this identification. The reported LD5o values for DEHP in rodents range from 14 to 128 g/kg and, on the basis of the lower figure, Geslar & Kartinos (loc. cit.) calculated that in a complete exchange transfusion using blood contaminated at a level of 11.5 mg/100 ml, a 70-kg adult would receive a quantity of D E H P some 2500 times less than the LDso.