A Comparison of the Acute Toxicity, Neuropathology, and Electrophysiology of N,N-Diethyl-m-toluamide and N,N-Dimethyl-2,2-diphenylacetamide in Rats

The insect repellent DEET and the structurally related herbicidediphenamid both cause ataxia associated with a spongiform myelinopathylargely confined to the cerebellar roof nuclei. This local myelinopathywas accompanied by the formation of neuronal cytoplasmic cleftsand was produced by a single dose of 1 to 3 g/kg N,N-diethyl-m-toluamide(DEET). These dose levels also produced a severe and often fatalprostration and clear electrophysiological signs of prolongedsuppressed seizure activity. Diphenamid produced an identicalmyelinopathy after doses of 0.8 to 1.5 g/kg but without thesevere prostration, suppressed seizures, or neuronal clefts.The effects of diphenamid were shown to be reversible over 3to 7 days by neuropathological, motor, and auditory evoked responseindices. Both compounds caused characteristic changes in auditoryevoked response which may be useful in clinical diagnosis. Sixother alkyl amides, two of which produce signs of CNS excitation,failed to produce myelinopathy at the maximum tolerated doses.Our findings show close parallels with a number of human casesof DEET poisoning and indicate that other amides, like diphenamid,also pose a potential hazard.     

Developmental Toxicity of CI-921, an Anilinoacridine Antitumor Agent

CI-921, an anilinoacridine compound active against leukemicand solid tumors, was evaluated for potential developmentaltoxicity. Intravenous injections of CI-921 in dextrose weregiven to female Sprague-Dawley rats (0.1, 0.5, and 1.0 mg/kg)on Gestation Days (GD) 6–15 and to female New ZealandWhite rabbits (0.1, 1.0 and 2.0 mg/kg) on GD 6–18. Appropriatevehicle and untreated controls were included. Maternal and fetalparameters, including external, visceral, and skeletal malformationsand variations, were assessed. Treatment of rats with 1.0 mg/kgresulted in maternal toxicity, manifested as reduced body weightgain and food consumption during and after treatment. Reducedfetal body weight, an increased incidence of stunted fetuses,malformations of the axial and appendicular skeleton, microphthalmia,and an increased number of anatomical variations (includinganomalies of the axial skeleton and apparent hydronephrosis)also occurred in rats at 1.0 mg/kg. Treatment of rabbits resultedin no apparent maternal toxicity. However, reduced fetal bodyweight, agenesis of the azygous lobe of the lung, and an increasedincidence of variations of the axial skeleton occurred at 2.0mg/kg in rabbits. These results indicate that CI-921, at thehighest dose tested in each species, produced developmentaltoxicity in the presence of maternal toxicity in rats, but inthe absence of maternal toxicity in rabbits.     

Cholesterol screening: observed cholesterol reduction in a prospective study in Norway

The general public of the City of Bergen, Norway was Invitedto participate in a cholesterol screening programme in October1988. Participants received the results of the cholesterol screeningand nutritional information from trained health personnel. Ashort questionnaire was mailed to all 354 participants 1–2weeks after the initial cholesterol screening. In March 1990,all participants were invited to have their cholesterol levelsre-examined. Psychosocial factors believed to be predictiveof future serum cholesterol changes were assessed at baselinealong with demographic variables. The majority of participants(61%) reduced their cholesterol level from October 1988 to March1990, and the average reduction in cholesterol level for thetotal population was 4.0%. Baseline cholesterol levels, beingconfident of one's own ability to change one's diet (self-efficacy),seeing heart disease risk reduction as very important, and maritalstatus were factors that significantly predicted successfulcholesterol reduction 18 months later.