O. Garth Fitzhugh

The injection of chemicals into the yolk sac of fertile eggs prior to incubation as a toxicity test

Abstract An evaluation of toxicity by injection of the chemical into the yolk sac of fertile eggs prior to incubation gave the following results: Water, propylene glycol, corn oil, peanut oil, isotonic saline solution, and isotonic glucose solution showed no toxicity or a very low order of toxicity. Mercuric chloride, lead acetate, selenium, triorthocresyl phosphate, p,p′-diamino-diphenylmethane, thiourea, Aroclor 1242, and dibutyl-tin-dilaurate showed a high order of toxicity and/or teratogenic effects at certain levels. Acetone, methanol, ethanol, n-butanol, diethylene glycol, ethylene glycol, isopropanol, di-2-ethylhexyl phthalate, hydrochloric acid, carbon tetrachloride, ethyl acetate, malathion, heptachlor, and styrene showed an intermediate order of toxicity.

Toxic properties of compounds related to safrole

Abstract Dihydrosafrole on chronic feeding produced benign and malignant esophageal tumors. Safrole is a hepatic carcinogen. Liver changes produced by isosafrole, safrole, and dihydrosafrole were of the same general type and included hepatic cell enlargement, which was usually focal and resulted in the formation of nodules; adenomatoid hyperplasia; cystic necrosis; fatty metamorphosis; and bile duct proliferation. The magnitude of liver changes was much greater with safrole than with the other two compounds. Safrole produced liver changes in mice. Similar treatment with the allybenzene and methylenedioxybenzene moieties of safrole produced changes only with methylenedioxybenzene and were less than that observed with the parent compound. This was confirmed in rats by Taylor et al. (1964). All compounds studied produced liver alterations with the exception of allylbenzene and piperonal.

Tumorigenic potential of Aldrin and Dieldrin for mice

Abstract Feeding 10 ppm of Aldrin or Dieldrin to C 3 HeB Fe mice for two years shortened their average life span by two months; significantly increased the incidence of histologically benign liver tumors; decreased the incidence of pneumonia (possibly owing to less cage crowding); and had no discernible effect on the incidence of mesenteric disease, intussusception, and other lesions of less frequent occurrence.

Chronic oral toxicities of four stearic acid emulsifiers

Four emulsifiers were fed in concentrations ranging from 2% to 25% in the diets of rats for two years; two of these were also fed to dogs for 19 to 20 months at 5% of the diet. Deleterious effects, largely limited to the higher levels of feeding, included increased liver weight with all substances at 25% except Myrj 52, plus the following for each substance. Span 60 caused significant increase in mortality of rats at the 10 and 25% levels, growth depression and kidney enlargement at 25%, two instances of enlargement of the common bile duct at the 25% level, and slight fatty changes in some livers. The feeding of 5% had no effect on dogs. Myrj 52 caused growth depression among male rats fed at 25% dietary concentration, diarrhea ranging from marked to slight from the 25% level downward, very slight to moderate enlargement of the cecum at the three higher levels, and very slight focal adenomatoid hyperplasia of the liver at 10% and 25%. Tween 60 produced marked diarrhea at 10% and 25%, enlargement of the cecum which was slight to moderate at the 25% level and less at 10%, and questionable fatty changes of a very slight degree in the livers of rats fed at 25%. Myrj 45 produced bladder stones in about one-third of the 25% male rats (27 of 87) with associated bladder tumors in nearly half of these (13 of 27). One female also had bladder stones. Bladder stones did not occur below the 25% feeding level. The incidence of spontaneous tumors was affected in male rats at the 2% and 5% levels. Livers were significantly heavier at 5% and 10% and slight fatty changes occurred in some livers, the numbers increasing with dosage. Dogs exhibited no distinct effect due to the feeding of 5% Myrj 45. Myverol 18-00 used as a control at 25% (the only level fed) caused a mild degree of renal tubular calcification.

Chronic oral toxicity of Ponceau 3R.

The results of two-year oral toxicity studies with Ponceau 3R using two strains of rats have been presented. Dosage levels were 5.0, 2.0, 1.0, and 0.5% for Osborne-Mendel rats and one dosage level of 2.0% for Bethesda Black rats. Preliminary results of the continuing dog and mouse studies are reported. Ponceau 3R at 5.0, 2.0, 1.0, and 0.5% of the diet produced high mortality, growth inhibition, and increased weight of the liver and kidneys. Malignant liver tumors occurred in both strains of rats at all dietary levels of Ponceau 3R, statistically significant (P < 0.01) in comparison with the controls at the 5.0% level of the Osborne-Mendel rats and the 2.0% level of the Bethesda Black animals. Incidence of benign liver tumors was also significant for all test levels. Marked weight loss and high mortality have been observed in dogs fed Ponceau 3R at dosage levels of 2.0% and 1.0%. After a feeding period of 32 weeks, changes in the liver were the most pronounced tissue changes. Increased mortality of C3HeBFe mice has been observed on 2.0% and 1.0% feeding levels. Hepatic adenomas and carcinomas have been observed on the 2.0% level.

Toxicity of Fourteen Volatile Chemicals as measured by the Chick Embryo Method.

Abstract The toxicity of each of 14 volatile chemicals was tested by use of a technique of injecting the chemicals into chick embryos. The toxicity data are given and compared with the Threshold Limit Values. There is a correlation of the data in general indicating that the chick embryo test for toxicity may be a useful tool in industrial toxicology.

Chronic rat and dog toxicity studies on tartrazine

Rats. Five groups of 24 Osborne-Mendel weanling rats, evenly divided by sex, were fed 5.0, 2.0, 1.0, 0.5, and 0.0% tartrazinemixed in their Purina laboratory chow diet for 2 years. Growth effect was negligible, and there was no effect on survival, hematology, or organ weights. The rats evidenced diarrhea at the 5% dosage level, slight diarrhea at the 2% level, and no diarrhea at the 1% level. The incidence of tumors and of the common incidental diseases was unaffected. No organ pathology attributable to treatment was noted except at the highest dosage level, where the feeding of tartrazine may have influenced the deposition of small amounts of gritty material in the renal pelvis of some of the surviving male rats. Dogs. Three groups of two male and two female beagles each were fed diets containing 2, 1, and 0% tartrazine for 2 years. No clinical symptoms of toxicity or hematologic abnormalities were noted during the study. No gross lesions were noted at autopsy. Histopathology was limited to the usual incidental lesions which, with the possible exception of pyloric gastritis in one high dose level dog, were not attributable to tartrazine toxicity.

Biochemical and toxicologic studies of Rhodamine B and 3,6-Diaminofluoran

Abstract 3,6-Diaminofluoran, the ultimate metabolite of Rhodamine B (tetraethyl-3,6-diaminofluoran) exerted fewer toxic effects in rats than Rhodamine B. The LD50 (intravenous) for Rhodamine B was 89.5 mg/kg compared to and LD50 of 140.0 mg/kg for 3,6-diaminofluoran by the same route. The growth of rats fed 1% Rhodamine B for 90 days was inhibited to a greater extent than that of rats fed 3,6-diaminofluoran at the same dietary level over the same period of time. Liver enlargement, the most significant abnormality at autopsy, occurred to a greater extent in the rats fed Rhodamine B. In vitro incubation studies showed that the metabolism of Rhodamine B occurred in the microsomes of liver cells and duplicated the stepwise de-ethylation process previously observed in the intact animal. Substantially all the orally ingested 3,6-diaminofluoran could be accounted for in the excreta. This indicates that the rat is unable to degrade this metabolite of Rhodamine B.

The subacute toxicity of four organic phosphates to dogs.

Abstract Dog plasma and red-cell cholinesterase determinations following the feeding of Dipterex, Chlorthion, methyl parathion, and Diazinon at several levels indicate that these materials are potent cholinesterase inhibitors. Dipterex, when fed at 500, 200, and 50 ppm in the diet, induced significant depression at 500 ppm and borderline depression at 200 ppm on both plasma and red-cell cholinesterase and no effect at 50 ppm. Chlorthion, fed at 15, 2, and 0.5 ppm, produced only questionable red-cell inhibition at 15 ppm, while no effect was noted at lower levels. Methyl parathion at 50, 20, and 5 ppm induced significant depression in the erythrocyte at the two higher levels, with significant depression at the 50-ppm level and only questionable depression noted in the plasma at the 20-ppm level. Diazinon at 75 and 0.75 ppm produced significant lowering of plasma cholinesterase, while 0.25 ppm was of no effect. Only the highest level of 75.0 ppm Diazinon produced significant red-cell cholinesterase depression.

Chronic toxicity of cubé

Abstract The effects of feeding cube powder to rats for two years at dietary levels of 50, 100, 250, 500, and 1000 ppm, and to dogs for 28 months at levels of 50, 150, and 400 ppm have been presented. Cube at all levels, except 50 ppm, inhibited growth of rats. No histopathologic change attributable to cube ingestion was noted at any level. The incidence of gross mammary tumors, nephritis, and pituitary lesions at the higher levels was less than in the controls. One dog at the 150 ppm level died after 20 months with hepatic pathology not attributed to cube toxicity. No clinical or hematologic effects were noted in the remaining dogs.