H. B. Haag

Tissue Distribution and Elimination of DDD and DDT Following Oral Administration to Dogs and Rats.

Conclusions 1. DDD and DDT when administered orally are stored in the tissues of the dog, the greatest storage appearing in the fat. 2. Similarly DDD and DDT are both stored in the fat of the rat. 3. Both DDD and DDT are transported across the placental barrier in the dog. 4. In the dog, a small proportion of orally administered DDD or DDT is excreted in the feces. Of the 2, DDD appears in greater amount. 5. When administered orally to the dog, neither DDD nor DDT are excreted as such in the urine. DDA is a urinary end-product common to both DDD and DDT, appearing in greater amount following DDD administration. We wish to extend our thanks to Dr. E. L. Stanley of the Rohm and Haas Company for performing the analytical procedures connected with this study.

Chronic toxicologic studies on isopropyl N-(3-chlorophenyl) carbamate (CIPC)

Abstract The feeding of isopropyl N -(3-chlorophenyl) carbamate to rats for two years and to dogs for one year at dietary concentrations of 0.2% or below produced no discernible adverse effects. At a dietary concentration of 2.0%, adverse effects occurred in both rats and dogs.

Toxicologic studies on 2,2-bis-(chlorophenyl)-2,2,2-trichloroethanol (kelthane)☆

Abstract 1. 1. Kelthane (2,2-bis-(chlorophenyl)-2,2,2-trichloroethanol), referred to below as K, was studied from the standpoints of its acute, subacute, and chronic toxicity, its storage in body fat when fed in the diet, and its effect on the ability of the adrenals to elaborate 17-hydroxycorticosteroids in response to ACTH administration. 2. 2. Oral LD 50 s (mg/kg) of the technical grade material were: male and female rats, 809 ± 33 and 684 ± 16, respectively; male rabbits, 1810 ± 350; dogs of mixed sex, >4000. 3. 3. Percutaneous LD 50 s in male rabbits were: technical grade K, 30% in dimethyl phthalate, 2.1 ± 0.3 g/kg; K emulsion concentrate (18.5% active ingredient), >10 ml/kg. 4. 4. Subacute percutaneous toxicity (minimal lethal dose) in male rabbits, as indicated by deaths occurring after the inunction of the test materials once daily, 5 days a week for 13 weeks, was found to be: technical grade K, 30% in dimethyl phthalate, 1.0 ml/kg; K emulsion concentrate, 18.5% active ingredient, 0.1 ml/kg; K wettable powder, 18.5% active ingredient, mixed with 2 parts of water, 0.5 g/kg. Technical grade K in dimethyl phthalate and the K emulsion concentrate were both irritating to the skin, the latter being markedly more destructive than the former. The K wettable powder was only mildly irritating. 5. 5. In the dog, K in sufficient dosage depresses the ability of the adrenals to elaborate 17-OH-corticosteroids in response to ACTH stimulation. 6. 6. Dogs fed 300 ppm or less of K in their diets for one year were unaffected. Deaths occurred at a dietary level of 900 ppm, but no signs of toxicity were observed in other animals which survived this feeding level. 7. 7. When rats were fed various concentrations of K in their diets for three months, survival was affected at 1250 ppm in both sexes. Growth was inhibited at the 100 ppm and higher levels in females, but only at 1250 ppm and higher in males. 8. 8. When rats were fed K in their diets for longer periods up to two years, survival was unaffected at levels below 1000 ppm. Females fed 250 ppm and higher levels and males 500 ppm and higher levels suffered a depression of growth. 9. 9. Lesions in the liver constituted the only treatment-related histopathologic changes seen in rats fed K containing diets. These changes varied in frequency and intensity with the dietary levels fed, with only a scattered incidence at levels below 1250 ppm. Increased liver-body weight ratios were observed. No histopathologic changes were seen in the dogs. There were no significant variations in hematological findings in treated animals as compared with controls. 10. 10. K is stored in the body fat of rats, but disappears after cessation of administration.

On the Relative Toxicity of Nicotine and Nornicotine

Summary Whereas, the mouse and the rabbit as regards acute toxicity are about equally sensitive to nornicotine, they differ markedly in their sensitivity to nicotine as well as in their ability to detoxify the two substances. In view of such species variation it would seem impractical to evaluate the relative toxicity of nicotine and nornicotine for man on the basis of animal data. Since nicotine and nornicotine are quite closely related structurally, these results again emphasize the hazard of transferring to man toxicity data on related compounds obtained on one species of animal.

Study of death due to combined action of alcohol and paraldehyde in man

The present study indicates that there is a combined action of alcohol and paraldehyde that may lead to death in some cases. Caution against overdosage should be exercised in their combined use. During the past several years, we have had the occasion to study nine cases in which the individual died suddenly and unexpectedly following paraldehyde therapy for acute alcoholism. Apparently these patients were in good health, other than for symptoms of alcolholism. Death occurred from 12 hour to 4 hours after administration of paraldehyde (30–60ml), and autopsy revealed no morphologic cause of death. Paraldehyde alone may produce death when the dose exceeds 120 ml, but the developing depression (coma) usually precedes death by at least 12 hours. Experiments with mice appear to confirm this combined action of alcohol and paraldehyde.

Further observations on effect on plasma 17-OH-corticosteroids in the dog of derivatives of 2,2-bis-(p-chlorophenyl)-1,1-dichloroethane (DDD, TDE).

Summary 1) The effect of 8 derivatives of 2.2-bis-(p-chlorophenyl) − 1,1-dichloroethane (DDD, TDE) on responsiveness of the adrenal cortex to ACTH, as determined by changes in plasma 17-hydroxycorticoids, has been studied in dogs. The following derivatives decreased the corticoid response: those with para-phenyl modifications; bromine substitution of the aliphatic chlorines; hydroxylation on the 2-position of the ethane moiety. No change in response was noted with a derivative in which hydrogen replaced chlorine in the 1-position of the ethane moiety, and with benzophenone, a possible DDD metabolite. Somewhat equivocal results were obtained with an ethylene analogue. 2) The relationship between these biochemical findings and the histopathologic effects recorded for this series of compounds is discussed.

Studies on Cigarette Smoke Irritation. II. The Role of Nicotine

Conclusions Neither nicotine nor its products of combustion contribute significantly per se to the edema-producing properties of cigarette smoke, although it may definitely increase the subjective sensations of irritation.

Studies on Cigarette Smoke Irritation. I. Determination of Edema-Producing Properties of Certain Types of Cigarette Tobaccos

Conclusions 1. Smoke from different types of cigarette tobaccos may differ significantly in edema-producing irritants. 2. Constituents are present in cigarette smoke, from at least certain types of tobaccos, which produce a degree of subjective irritation disproportionately greater than that which might be expected on the basis of their edema-producing properties.

Studies on the acute toxicity and irritating properties of the congeners in whisky

Abstract The acute oral toxicity of a series of congeneric fractions prepared from whisky, their synthetic prototypes, furfural, and purified ethyl alcohol has been determined in rats. Of these materials furfural, an found to be the most toxic (LD50 = 0.135 ± 0.015 g/kg) and purified ethyl alcohol the least toxic (LD50 = 10.4 ± 0.75 g/kg). With the exception of the acid fraction, the effects of the other congeners came on more quickly and in surviving animals disappeared more quickly than was the case with ethyl alcohol. The acutely irritating effects of these same materials were studied on the rabbit eye. The acid fractions were found to be by far the most irritating, the other congeners fell in a middle range between this fraction and purified ethyl alcohol, which was the least irritating. The role which the congeners might play in the over-all pharmacologic action of whisky remains largely to be determined. The present state of knowledge would seem to suggest that their concentrations in whisky be kept in general at a minimal level compatible with their satisfactory contribution to its flavor, bouquet, and color.

Response of the Exteriorized Spleen to Ephedrine, Acetyl Choline, Pilocarpine and Pituitrin

Conclusions Injection of acetyl choline, pilocarpine, ephedrine, and pituitrin (S) into the saphenous vein causes significant contraction of the exteriorized spleen in conscious dogs. In 2 single observations, chloroform inhalation caused contraction and sodium amytal (intravenously) caused relaxation of the exteriorized spleen.