William B. Deichmann

Effects of environmental temperature on the acute toxicity of a number of compounds in rats.

Abstract The acute intraperitoneal toxicity of each of 58 compounds was determined in albino rats exposed to three different environmental temperatures: 8°, 26°, and 36°C. Except for strychnine, chlorpromazine, and promazine, all compounds were most toxic at 36°C. Strychnine was equally toxic at 8° and 36°C, while promazine and chlorpromazine were most toxic at 8°C.

Toxicology and No-Effect levels of aldrin and dieldrin

Some of the critical values have been selected from the various criteria just reviewed and are listed below. Acute oral toxicity. Twenty to 70 mg/kg, aldrin or dieldrin, 12 species. The estimated lethal dose for man is approximately 5 g. Mortality on repeated doses. (a) Short-term: quail, dog, turkey, mouse, <25 ppm; cat and pheasant, <100 ppm; cow, sheep, and rabbit, <165 ppm; rat, <300 ppm. (b) Short-term or chronic: quail, 0.5 ppm of aldrin, 1 ppm of dieldrin; monkey, 5 ppm of dieldrin; mouse, 10 ppm of aldrin and dieldrin; dog, 10 ppm of aldrin, 25 ppm of dieldrin; turkey, 12.5 ppm of aldrin; rabbit, 80 ppm of aldrin, 20 ppm of dieldrin; rat, 100–150 ppm of aldrin or dieldrin. Body weight. No change at 2 ppm or less. Changes: monkey, 2.5 ppm of dieldrin; male turkey, 3 ppm of aldrin; sheep and cow, 7 ppm of aldrin in hay; dog (pup), 10–25 ppm of aldrin; rat, 300 ppm of aldrin or dieldrin. Food consumption, hematology, urine analyses. Not sensitive. Liver weight: body weight increase. Rat, 0.5, 2.5 ppm; dog, 3 ppm of aldrin, 1 ppm of dieldrin. Pathology. Rat, 2 ppm of aldrin, 0.5 ppm of dieldrin; dog, 3 ppm of aldrin, 8 ppm of dieldrin; mouse, 10 ppm of aldrin or dieldrin. Reproduction. Rat, fewer pregnancies, greater mortality of pups, 12.5 ppm of aldrin, 2.5 ppm of dieldrin; dog, greater mortality of pups, 8 ppm of aldrin, 25 ppm of dieldrin; sheep, greater mortality of lambs, 25 ppm of dieldrin; quail, some changes at 1–10 ppm of dieldrin; pheasant, 25 ppm of dieldrin. Human. Typical diets in England and in the United States are estimated to contain 0.001–0.002 ppm of dieldrin. Dieldrin concentrations in human fat probably average about 0.2 ppm. Blood concentrations exceeded 20 μg per 100 ml in exposed patients showing signs of intoxication.

Acute toxicity of combinations of pesticides.

Abstract The acute oral toxicity (LD 50 ) of equitoxic doses of combinations of 15 pesticides was determined in rats and mice. The Expected LD 50 of a “mixture” was compared with the Observed or Actual LD 50 and expressed as a ratio. The compounds studied included the chlorinated hydrocarbons aldrin, Aramite, chlordane, DDT, dieldrin, endrin, methoxychlor, and toxaphene; the organic phosphates Delnav, diazinon, malathion, parathion, trithion, and V-C 13; and a carbamate, carbaryl. Most of the combinations of two or three of these pesticides induced essentially additive effects in both species, with the exception of the combination of aldrin and chlordane. These two compounds induced an additive effect in rats, while in mice there was a potentiation. Less than additive effects (antagonism or protection) were noted with: aldrin plus diazinon, malathion, V-C 13, Delnav, or trithion (rat); DDT plus malathion, V-C 13, or diazinon (rat); toxaphene plus trithion (rat); endrin plus DDT or Delnav (mouse); and aldrin plus parathion (mouse). More than additive effects (possibly some degree of potentiation) were noted with: endrin plus chlordane or aldrin (mouse); Aramite plus Delnav, diazinon, or parathion (mouse); methoxychlor plus chlordane, dieldrin or Delnav (mouse); aldrin plus chlordane (mouse); and chlordane plus parathion plus malathion (mouse). The data in the combinations of three pesticides did not reveal effects of toxicity which could not have been predicted from the combinations of two compounds.

The debate on DDT

The paper reviews the early toxicologic and pharmacologic studies carried out by the author and his associates from 1943 to 1947, which were largely responsible for launching DDT as an agent for the control of typhus, malaria, yellow fever, and related vector-borne diseases. After reviewing recent studies conducted at the University of Miami, which dealt with organochlorine pesticides in human tissues, the tumorigenicity of aldrin, dieldrin and endrin (rat), six-generation mouse and three-generation dog reproduction studies, synergism of DDT and aldrin (dog), and the fate of DDT and aldrin during a period of severe starvation (rat), it is pointed out that it is primarily the overuse and misuse of DDT in pest control that have caused the pollution in our ecology. It is emphasized that the requirements for pest control differ the world over and that it must therefore be left to the national regulatory agencies to legislate the safe use of DDT and related pesticides. It is recommended that future human and animal studies with DDT and its derivatives give consideration to: (a) the balance and metabolism of the various hormones, (b) reproduction (estrus, libido, mammary development, milk production, (c) hepatic microsomal enzyme activities, (d) cancer prevention and cancer production, (e) excessive body weight changes induced by disease, unbalanced diet or starvation, and (f) the effects of DDT and its derivatives when absorbed in combination with other related and even unrelated compounds.ZusammenfassungDie Arbeit gibt einen Überblick über die frühen toxikologischen und pharmakologischen Untersuchungen, die der Autor und seine Mitarbeiter von 1943 bis 1947 ausführten, und die zum großen Teil verantwortlich waren für den Einsatz von DDT zur Bekämpfung von Typhus, Malaria, Gelbfieber und ähnlichen Insekten-übertragenen Erkrankungen. Nach Schilderung neuerer Untersuchungen, ausgeführt an der University of Miami, die Bestimmungen OrganochlorPestiziden in menschlichen Geweben, die Tumorhemmung durch Aldrin, Dieldrin und Endrin (Ratte), Generationsversuche über 6 Generationen an der Maus und 3 Generationen am Hund, den Synergismus von DDT und Aldrin (Hund) und das Verhalten von DDT und Aldrin im schweren Hungerzustand (Ratte) behandeln, wird ausgeführt, daß in erster Linie übertriebene Anwendung und Mißbrauch von DDT bei der Schädlingsbekämpfung die Verunreinigung in unserer Umwelt bewirkt haben. Es wird hervorgehoben, daß die Anforderungen an die Schädlingsbekämpfung an verschiedenen Stellen der Welt sich unterscheiden, und daß es daher den nationalen Kontrollbehörden überlassen bleiben müsse, den gesundheitlich unbedenklichen Gebrauch von DDT und verwandten Schädlingsbekämpfungsmitteln auf dem Verordnungswege zu regeln. Für künftige Untersuchungen an Mensch und Tieren mit DDT und seinen Abkömmlingen wird folgendes zur Beachtung empfohlen: a) Regulation und Stoffwechsel der verschiedenen Hormone, b) die Fortpflanzung (Oestrus, Libido, Mammaentwicklung, Milchbildung), c) die Aktivität mikrosomaler Leberenzyme, d) Krebshemmung und Krebserzeugung, e) durch Krankheit, Fehlernährung oder Hunger hervorgerufene exzessive Körpergewichtsänderungen und f) die Wirkungen von DDT und seiner Abkömmlinge nach Resorption in Verbindung mit verwandten und auch nicht-verwandten Verbindungen.

Organochlorine pesticides and liver cancer deaths in the United States, 1930–1972☆

Abstract Animal studies have shown the liver to be the primary target organ following prolonged periods of absorption of toxic doses of organochlorine pesticides. Therefore, the core of our presentation is aimed at the liver. Since studies in our laboratory have been concerned primarily with DDT, aldrin, and dieldrin, these compounds are being given primary consideration.

The hemopoietic tissue toxicity of benzene vapors.

Abstract Groups of 40 rats (50 rats in experiment no. 8 and 20 rats in the control experiment) were exposed to benzene vapor concentrations of 831, 65, 61, 47, 44, 31, 29, and 15 parts per million parts of air respectively, for 5 hours per day, on 4 days of the week (experiment no. 8, 7 hours of exposure on 5 days of the week), for periods ranging from 5 weeks to 7 months. A significant leucopenia resulted after 2–4 weeks of exposure to 831, 65, and 61 ppm, respectively. Exposure to 47 and 44 ppm induced a moderate but definite leucopenia after 5–8 weeks of exposure. The number of red blood cells and the concentration of hemoglobin in the circulating blood were not affected by these exposures. Exposure to 31 ppm of benzene (4 months), 29 ppm (3 months) and 15 ppm (7 months) did not induce changes in hemopoietic tissue. The hemopoietic tissue toxicity of a mixture of benzene and hexane was due to the benzene fraction of the mixture. The most significant and constant pathologic changes noted were found in the lungs (chronic bronchopneumonia) and spleen (excess of hemosiderin). The lung changes found were similar in extent and degree in the control and in experimental animals. The degree of hemosiderosis in the control rats was rated as “slight”; it was “more marked” in the experimental animals. The data presented here indicate that benzene vapors have greater hemopoietic tissue toxicity than is commonly recognized. Because one of a number of factors may render a persons hemopoietic tissues more than ordinarily susceptible to benzene, it seems advisable to consider reevaluation of the Maximum Allowable Concentration of 25 ppm. The margin of safety presently accepted for benzene is small compared with the margins employed in other fields of public health.

The chronic toxicity of octadecylamine in the rat--a supplemental report.

Abstract Rats fed diets containing octadecylamine at levels of 200 and 500 ppm, respectively, for a two-year period exhibited no signs of toxicity and no pathologic changes attributable to the feeding of this compound. Food consumption, increase in body weight, and rate of survival of the rats were normal. These results confirm the conclusions of our previous report.

Hematologic effects of Crotalus adamanteus (rattlesnake) venom

Summary1.Crotalus adamanteus venom produces a striking neutrophilic leukocytosis in dogs whether administered intramuscularly or intravenously.2.Intramuscular administration of a lethal dose (1.28 mg/kg) of crystallineCrotalus adamanteus venom to dogs also produced: a terminal increase in serum nonprotein nitrogen, a hypoproteinemia, a reduction in plasma fibrinogen, and a terminal shortening of coagulation time.3.It is noteworthy that no effects of this venom were noted on the serum bilirubin concentration. It follows, therefore, that contrary to existing impressions this venom does not produce any significant degree of hemolysis in vivo.4.In addition, the intramuscular administration ofCrotalus adamanteus venom was found not to significantly affect the: blood glucose concentration, the platelet count, the plasma prothrombin time, the prothrombin time withRussells viper venom, the prothrombin consumption, the thromboplastin generation, or the fibrinolysin activity. Two of five dogs showed a transient rise in erythrocyte count and hematocrit.5.By contrast,Naja flava venom did not produce neutrophilic leukocytosis when administered in a subacutely toxic dose (0.2 mg/kg/day).6.Intravenously administeredCrotalus adamanteus venom did not counteract the neutropenic effects of orally administered Myleran in dogs.

F.D.A. requirements for food additives in the U.S.A.

ConclusionsThe methods required to demonstrate that a particular food additive is safe for human consumption depend on the compound involved and on the specific use of the material. In other words, each additive presents a specific and a different problem. Therefore, the toxicological investigation required may range anywhere from a few simple tests to a most comprehensive and time consuming investigation. A most important factor in each of these studies is the investigator himself. There is no simple formula, and certainly no substitute for the mature and considered judgement of the man who by experience and training is qualified to interpret the experimental data.