We found that the distribution of the lipophilic chemotherapeutic agent o,p'-DDD (mitotane) among serum (lipo)proteins was altered in hypertriglyceridemia, with relatively more o,p'-DDD accumulating in the chylomicron and very-low-density lipoprotein (VLDL) fraction. Intralipid, an artificial chylomicron emulsion, or isolated VLDL could extract o,p'-DDD from the other serum (lipo)proteins. There was an inverse relationship between the relative amount of o,p'-DDD found in the fraction exhibiting a density of less than 1.006 g/ml (chylomicrons plus VLDL) and the relative amount observed in the LDL or HDL fractions of serum. Our results indicate that hypertriglyceridemia may impede the entry of o,p'-DDD into the brain or the adrenals. For therapeutic monitoring of o,p'-DDD levels in severe hypertriglyceridemia, we recommend that the chylomicron and VLDL fraction first be removed from the serum by ultracentrifugation.

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The Chick Embryo Test As Used in the Study of the Toxicity of Certain Dithiocarbamates. GEBHARDT, D. 0. E., and VAN LOGTEN, M. J. (1968). Toxicol. Appl. Pharmacol. 13, 316-324. The toxicities of six dithiocarbamates: bis(dimethy1 thiocarbamoyl) disulfide (thiram), zinc dimethyldithiocarbamate (ziram), ferric dimethyldithiocarbamate (ferbam), bis(dimethyl thiocarbamoyl) ethylene bis(dithiocarbamate) (triaram), sodium diethyl dithiocarbamate (NaDEDC), and sodium ethylene bis(dithiocarbamate) (nabam) were determined in the chick embryo. The substances were dissolved in propylene glycol and injected in the air chamber prior to incubation. Injection in the yolk sac on any day of development or in the air chamber after the first day was unsuitable for the assessment of an LD50. With the exception of nabam, the dithiocarbamates were extremely toxic for the early chick embryo. Cysteine injected simultaneously in the air chamber protected the embryos from the toxic effect of thiram or ziram but not from the action of triaram. It is suggested that the former two dithiocarbamates are reduced by cysteine to less toxic compounds.In recent years more attention has been paid to the methodology of testing the toxicity of chemical substances in the developing chick. Ridgway and Karnofsky (1952) studied the effect of various metals on the chick embryo. They injected these substances in the yolk on the day 4 or 8 or on the chorioallantois on day 8 and discovered that the place and time of injection were important factors in determining the responsiveness of the embryo. A difference in sensitivity depending on the site of injection was also found by Verrett et al. (1964), who showed that the toxicity of aflatoxin when injected into the air chamber was twice as high as when injected into the yolk.Other comprehensive studies on the injection of chemicals into eggs were performed by McLaughlin and co-workers (McLaughlin et al

Pregnant mice were injected once with 10 or 20 mg/kg cyclophosphamide. A large embryolethal effect was induced by treatment on the 3rd and on the 8th and 9th days of pregnancy. Mortality was probably due to a direct effect of cyclophosphamide on the embryos. Limb malformations were induced at a later stage; therefore it appears that embryolethality and teratogenicity are separable processes. The anomalies consisted of synostoses, retardation of ossification, and poly‐ and oligodactyly. Polydactyly was induced at an earlier stage than oligodactyly.

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