Showing papers in "Journal of Toxicology and Environmental Health in 1981"
TL;DR: Observations suggest that the lipid peroxidation associated with Cd and Hg is not necessarily responsible for the loss of cell viability induced by these two metals.
Abstract: Various mechanisms, including increases in lipid peroxidation, have been proposed to account for metal-induced cellular injury. By comparing several metals in the same cell population, it is possible to determine whether a correlation exists between ability to produce cell injury and ability to alter parameters pertaining to a particular mechanism. Of particular interest in this study was the relation between metal-induced cytotoxicity and increases in lipid peroxidation. The effects of Cr, Mn, Zn, Ni, Pb, Se, V, Fe, Cd, Hg, Cu, at final concentrations of 1-1000 microM, on the viability of isolated hepatocytes were therefore examined by assessing the loss of intracellular K+ and aspartate aminotransferase (AST). Simultaneously, the ability of the metals to induce lipid peroxidation, as measured by an increase in thiobarbituric acid (TBA) reactants, was assessed. Hg and Cu required the lowest concentration to produce cellular injury, while Cd produced less dramatic changes in cell viability and Fe at 1000 microM produced only a small decrease in intracellular K+. The largest absolute increases in lipid peroxidation were found in the presence of V, followed by Fe and Hg, with Cd and Se causing the smallest increase in TBA reactants. These observations suggest that the lipid peroxidation associated with Cd and Hg is not necessarily responsible for the loss of cell viability induced by these two metals.
115 citations
TL;DR: Estimates of the critical level by beta 2-microglobulin and urinary protein measurements yielded critical values of 31-42 mg Cd for the whole kidney (300-400 microgram/g for the renal cortex).
Abstract: Cadmium was measured in vivo in the left kidney and liver of 82 industrially exposed workers and 10 control subjects. The range of Cd values for the industrial group was 0.9–57 mg for the whole kidney and 0.8–120 ppm for the liver, compared to 0.4–11.8 mg and 0.6–7.9 ppm for the control group. Below 40 ppm in the liver, the kidney Cd burden tended to increase with increasing liver concentration. Above 40 ppm, the kidney Cd content decreased as the liver concentration increased. This biphasic relation between Cd in the kidney and the liver for all subjects showed a critical level of approximately 31 mg Cd In the kidney. Estimates of the critical level by s2‐microg/obulin and urinary protein measurements yielded critical values of 31–42 mg Cd for the whole kidney (300–400 μg/g for the renal cortex).
99 citations
TL;DR: In determining the carcinogenicity of chemical tested in a National Cancer Institute (NCI) bioassays, the following criteria are considered: the adequacy of the bioassay data, the presence of significantly increased incidences of tumor, the adequency of the number of animals at risk of developing tumors, and other factors that may influence an evaluation.
Abstract: In determining the carcinogenicity of a chemical tested in a National Cancer Institute (NCI) bioassay, the following criteria are considered: (1) the adequacy of the bioassay data, (2) the presence of significantly increased incidences of tumors, (3) the adequacy of the number of animals at risk of developing tumors, (4) the adequacy of the dose of chemical administered, (5) the etiology and pathogenesis of the lesions, and (6) other factors that may influence an evaluation, such as o shortened latency period for tumor formation in dosed animals or the stability of the chemical. A decision tree for evaluating these factors is presented. A summary of the results of 200 NCI carcinogen bioassays is also reported. These procedures are presented in the hope that they may serve as discussion points for future developments In the field.
96 citations
TL;DR: Orchardists from the Okanagan Valley in British Columbia who were involved in mixing, loading, and application with ultra-low volume air blast equipment had quantifiable levels of alkyl phosphates following exposure, and 24-h urine samples provided a more reliable estimate than first morning voids.
Abstract: Exposure to and absorption of Guthion 50 W.P. (azinphos‐methyl) were estimated in orchardists from the Okanagan Valley in British Columbia who were involved in mixing, loading, and application with ultra‐low volume air blast equipment. Air monitoring and patch techniques were used to estimate exposure, and alkyl phosphate excretion and cholinesterase inhibition were measured to estimate absorption. All workers were issued with standardized cotton shirts, trousers, and long‐sleeved coveralls. All wore half‐face respirators, gloves, boots, and hats. Eight wore rubberized protective clothing in addition. The indirect method of measuring urinary metabolites appeared to be the most sensitive. All workers had quantifiable levels of alkyl phosphates following exposure, and the 24‐h urine samples provided a more reliable estimate than first morning voids. A high correlation was observed between 48‐h alkyl phosphate excretion and amount of active ingredient sprayed. A fluorescent tracer was added to the tank along...
94 citations
TL;DR: Findings suggest that measurements of aflatoxin in whole corn might underestimate aflatoxins levels in corn dust aerosols.
Abstract: Samples of airborne grain dust representing a variety of grains were examined for the presence of aflatoxins. Although aflatoxins could not be detected in most of the samples, one corn sample contained 130 ppb aflatoxin B1. When the components of this sample were separated according to aerodynamic diameter and analyzed for aflatoxins, it was found that particles with diameters 7–11 urn and <7 μm had much higher levels of aflatoxins than the sample as a whole. These findings suggest that measurements of aflatoxin in whole corn might underestimate aflatoxin levels in corn dust aerosols.
86 citations
TL;DR: The presence of polycyclic aromatic hydrocarbons in petroleum, including BaP, chrysene, and DMBA, significantly enhances the overall embryotoxicity in avian species.
Abstract: Studies with different avian species have revealed that surface applications of microiiter amounts of some crude and fuel oils that coat less than 10% of the egg surface result in considerable reduction in hatching with teratogenicity and stunted growth. Other studies have shown that the embryotoxicity is dependent on the aromatic hydrocarbon content, further suggesting that the toxicity is due to causes other than asphyxia. In the present study the effects of three polycyclic aromatic hydrocarbons identified in petroleum were examined on mallard (Anas platyrhynchos) embryo development. Addition of benzo[a]‐pyrene (BaP), chrysene, or 7,12‐dimethylbenz[a]anthracene (DMBA) to a synthetic petroleum hydrocarbon mixture of known composition and relatively low embryotoxicity resulted in embryotoxicity that was enhanced or equal to that of crude oil when 10 μl was applied externally to eggs at 72 h of development. The order of ability to enhance embryotoxicity was DMBA > BaP > chrysene. The temporal pattern of e...
85 citations
TL;DR: Blood methanol concentrations were measured in 30 normal adult subjects administered aspartame, a dipeptide methyl ester, and no changes were noted in any of the blood chemistry profile parameters measured 24 h after aspartam ingestion, compared to values noted before administration.
Abstract: Blood methanol concentrations were measured in 30 normal adult subjects administered aspartame, a dipeptide methyl ester. The doses studied included the 99th percentile of projected daily ingestion (34 mg/kg body weight) and three doses considered to be in the abuse range (100, 150, and 200 mg/kg body weight). Methanol concentrations were below the level of detection (0.4 mg/dl) in the blood of the 12 normal subjects who ingested aspartame at 34 mg/kg. They were significantly elevated (p less than or equal to 0 .001) after ingestion of each abuse dose, with the mean peak blood methanol concentrations and the areas under the blood methanol concentration-time curve increasing in proportion to dose. Mean (+/- SD) peak blood methanol concentrations were 1.27 +/- 0.48 mg/dl at the 100 mg/kg dose, 2.14 +/- 0.35 mg/dl at the 150 mg/kg dose, and 2.58 +/- 0.78 mg/dl at the 200 mg/kg dose. Blood methanol concentrations returned to predosing levels by 8 h after administration of the 100 mg/kg dose. Methanol was still detected in the blood 8 h after the subjects had ingested aspartame at 150 or 200 mg/kg. Blood formate analyses were carried out in the 6 subjects who ingested aspartame at 200 mg/kg, since recent studies indicate that the toxic effects of methanol are due to formate accumulation. No significant increase in blood formate concentrations over predosing concentrations was noted. No changes were noted in any of the blood chemistry profile parameters measured 24 h after aspartame ingestion, compared to values noted before administration. Similarly, no differences were noted in ophthalmologic examinations carried out before and after aspartame loading.
82 citations
TL;DR: When 1,3-dinitrobenzene (1,3−DNB) was given to rats orally as a 1% suspension in corn oil, the LD50 was 83 mg/kg with fiducial limits 56-124 mg/ kg as discussed by the authors.
Abstract: When 1,3‐dinitrobenzene (1,3‐DNB) was given to rats orally as a 1% suspension in corn oil, the LD50 was 83 mg/kg with fiducial limits 56–124 mg/kg. The compound was equally toxic in both sexes. Signs of toxicity included reduction in ambulatory motion, ataxia, weakness, dyspnea, rapid heartbeat, cyanosis, coma, and eventual respiratory failure. When 1,3‐DNB was added to the daily drinking water in concentrations of 50, 100, and 200 mg/l for 8 wk, 3 of 6 male rats receiving the highest concentration died during wk 4 and another died during wk 5. Of a like number of females, one died during wk 6 and another during the wk 7. All other animals survived. Growth rate was reduced in both sexes and at 200 mg/l 1,3‐DNB in the water supply the animals lost weight. There were mild, consistent reductions in hematocrit and hemoglobin values. Enlarged spleens were present in both sexes at all concentrations; fibrosis with deposition of hemosiderin was present in all rats at 200 mg/l 1,3‐DNB. Testicutar atrophy was evid...
79 citations
TL;DR: The cancer morbidity in a large group of male German agricultural workers exposed to pesticides was investigated through a retrospective cohort study, and a positive correlation between the duration of employment and the mortality due to lung cancer suggested a dose-effect relation.
Abstract: The cancer morbidity in a large group of male German agricultural workers exposed to pesticides was investigated through a retrospective cohort study. A total of 169 malignant tumors were diagnosed in 1658 men who began to work with pesticides between 1948 and 1972, and who continued this type of activity for at least 5 yr. The SMR (standardized mortality ratio) of 2.0 for lung cancer morbidity (mortality) in these pesticide-exposed subjects was significantly higher than that for the general male population of the German Democratic Republic. A positive correlation between the duration of employment and the mortality due to lung cancer (mainly undifferentiated and small-cell carcinomas) suggested a dose-effect relation. The smoking habits of the exposed men did not differ from those of the general male population of the German Democratic Republic. Because the subjects had been exposed to many different substances, the study does not permit any conclusions to be drawn in respect to the carcinogenicity of individual pesticides. The increased mortality due to lung cancer is presumably the result of an additive effect of different pesticide ingredients or of by-products whose carcinogenic effect has been definitely or tentatively established through experimental or epidemiologic studies (e.g. arsenic, asbestos, chlorinated dibenzodioxins, DDT). The results of the present investigation emphasize the need for effective measures to protect workers during occupational contact with pesticides.
76 citations
TL;DR: Histological studies showed that when chlordecone was fed to sexually immature quail, the oviducts exhibited accelerated growth, cytodifferentiation, cellular hypertrophy, secretory activity, and maturation, and it stimulated granular endoplasmic reticulum and Golgi development and induced fullsecretory activity in the cytoplasm of estrogen‐sensitive qua...
Abstract: Effects of the insecticide chlordecone (Kepone) on female reproduction in birds and mammals were reviewed. In different avian species, chlordecone inhibited or reduced reproduction and decreased egg hatchability and survival of the newborn. In Japanese quail, chronic chlordecone ingestion decreased total egg production and clutch size and increased egg breakage. Eggs produced by treated quail were significantly weaker and thinner. Chlordecone also decreased follicular development, induced ovarian regression, and inhibited ovulation and egg laying. Histological studies showed that when chlordecone was fed to sexually immature quail, the oviducts exhibited accelerated growth, cytodifferentiation, cellular hypertrophy, secretory activity, and maturation. Ultrastructure of the oviduct surface showed increased growth of microvilli and profuse ciliation. Chlordecone also stimulated granular endoplasmic reticulum and Golgi development and induced full secretory activity in the cytoplasm of estrogen‐sensitive qua...
68 citations
TL;DR: Rat serum carboxylesterase and cholinesterase were inhibited for prolonged periods after a single oral dose of O,O,S-trimethyl phosphorothioate, but the duration of inhibition was significantly less when the toxicant contained 1% O,o,O-trIMethyl isomer.
Abstract: O,O,S‐Trimethyl phosphorothioate, an impurity in several technical organophosphorus insecticides, when administered orally to rats at single doses as low as 15 mg/kg caused delayed mortality, with death occurring 4–22 d after treatment. Delayed toxic signs were also observed in mice, but mice were generally less sensitive than rats. O,O,S‐Triethyl phosphorothioate and O,S,S‐trimethyl phosphorodithioate induced the same signs of intoxication at slightly higher doses. Rats treated with O,O,S‐trimethyl phosphorothioate refused food and water within 24 h after treatment and did not eat or drink until the time of death. Neither injection of nutrient solution nor atropine served to reduce or block intoxication. However, the isomeric O,O,O‐trimethyl phosphorothioate was a potent antagonist of the toxicity of O,O,S‐trimethyl phosphorothioate. As little as 1% of the O,O,O‐trimethyl isomer protected rats from the intoxicating effects of the O,O,S‐trimethyl isomer at doses as high as 200 mg/kg. Rat serum carboxylest...
TL;DR: The procedures described are capable of determining blood concentrations down to 50-100 pg/ml, permitting identification of abrin and ricin poisoning and monitoring of the blood concentrations in cancer patients treated with these agents.
Abstract: Radioimmunoassays for abrin and ricin are described. There is little cross-reactivity between the two toxins. The procedures described are capable of determining blood concentrations down to 50-100 pg/ml, permitting identification of abrin and ricin poisoning and monitoring of the blood concentrations in cancer patients treated with these agents.
TL;DR: Exposure was highly correlated with consumption, but their was no correlation between any estimate of exposure and brand yield when level of consumption was held constant, and a comparison of levels of carboxyhemoglobin and plasma thiocyanate revealed little difference between the two groups.
Abstract: Yields of chemical constituents such as tar, nicotine, CO, and HCN defined by smoking machines are commonly assumed to provide a reasonable indication of the relative hazard associated with smoking a given brand of cigarette. Results reported here suggest that this assumption should be carefully reexamined. A total of 240 subjects, representing a wide range of smoking and brand characteristics, were recruited for an investigation of possible relations between brand yields and exposure (levels of carboxyhemoglobin, breath CO, plasma cotinine, plasma thiocyanate, and saliva thiocyanate). Exposure was highly correlated with consumption (number of cigarettes per day), but there was no correlation between any estimate of exposure and brand yield when level of consumption was held constant. In addition, a comparison of levels of carboxyhemoglobin and plasma thiocyanate for 16 smokers of “low‐hazard” and 15 smokers of “high‐hazard” cigarette brands revealed little difference between the two groups, even though a...
TL;DR: Flow-through, acute, and early life stage (28-d after hatch) toxicity tests were performed with eight chemical on a saltwater fish, sheepshead minnows, and chemical effects on survival, growth, and development were determined.
Abstract: Flow-through, acute (96-h), and early life stage (28-d after hatch) toxicity tests were performed with eight chemical on a saltwater fish, sheepshead minnows (Cyprinodon variegatus). Chemical effects on survival, growth, and development were determined. Maximum acceptable toxicant concentrations (MATCs) were greater than 3.2 less than 7.7 mg/l for toluene, greater than 0.52 greater than 0.97 mg/l for acenaphthene, greater than 80 less than 156 mg/l for isophorone, greater than 10 less than 16 mg/l for 4-nitrophenol, greater than 4.8 less than 8.5 mg/l for bromoform, greater than 0.39 less than 0.79 mg/l for 1-chloronaphthalene, greater than 0.09 less than 0.18 mg/l for 1, 2, 4, 5-tetrachlorobenzene, and less than 0.36 mg/l for 2, 4-dichloro-6-methylphenol; application factors were 0.25-0.59, 0.17-0.31, greater than or equal to 0.57, 0.31-0.50, greater than or equal to 0.68, greater than or equal to 0.56, 0.27-0.54, and less than 0.10. respectively. Test results reported here were compared with results of static, acute toxicity tests conducted previously with six species of aquatic organisms and the same chemicals.
TL;DR: Protective properties of some metals seen in vivo can be demonstrated at the cellular level and protective effects of metals in general on Cd-induced cellular toxicity are not due to a decrease in either Cd uptake or lipid peroxidation.
Abstract: Interactions between Cd and other metal ions are important from both nutritional and toxicological aspects. As Cd is toxic to isolated hepatocytes, these cells can be used to investigate the effects of other metals on Cd‐induced cellular injury. Isolated hepatocytes were incubated at 37°C with vehicle (saline); Cd (200 or 400 μM); or Cd plus Cr, Mn, Zn, Ni, Pb, Se, or Fe (200–1000 μM). Evidence of cellular injury was assessed by loss of Intracellular K+ and aspartate aminotransferase from the hepatocytes. Effects on lipid peroxidation, as measured by concentration of thiobarbituric acid reactants, were assessed. Uptake of 109Cd and interaction of the other metal ions with this accumulation were also quantitated. Cell injury due to Cd was consistently reduced by Cr, Mn, Zn, Pb, and Fe. Lipid peroxidation due to Cd was inhibited by Cr, Mn, and Zn. All the metals except Ni produced an increase in the amount of Cd accumulated by hepatocytes. There was no consistent relation between reduction of cellular toxic...
TL;DR: The effects of body and tissue weights, gross metabolic performance, O2 consumption, systolic blood pressure, various blood parameters, and intestinal transit time associated with 3-mo exposures of young adult male rats to chemically verified concentrations of methyl mercaptan vapor are summarized in this report.
Abstract: Acute inhalation experiments were conducted to determine 24-h LC50 values for adult Sprague-Dawley rats of both sexes exposed to vapors of methyl mercaptan and other reduced-S compounds for 4 h periods. Using calculated gas concentrations, the following LC50 value for each gas and combination was determined: metyhl mercaptan, 675 ppm; dimethyl sulfide, 40,250 ppm; dimethyl disulfide, 805 ppm; hydrogen sulfide, 444 ppm; and an equimolar mixture of methyl mercaptan, dimethyl sulfide, and dimethyl disulfide, 550 ppm. The effects of body and tissue weights, gross metabolic performance, O2 consumption, systolic blood pressure, various blood parameters, and intestinal transit time associated with 3-mo exposures of young adult male rats to chemically verified concentrations of 2, 17, and 57 ppm methyl mercaptan vapor are summarized in this report. No mortality was experienced by any group. Histopathological findings were essentially nil except for microscopic suggestions of liver damage. The most readily apparent phenomenon was the decrease in body weight. Average values of terminal body weights for all exposed groups were lower than that for the sham control group. This difference was significant in the 57 ppm group and followed a statistically significant dose-related trend.
TL;DR: At approximately equimolar doses, DMBA appeared to be more potent than BaP in enhancing the development of lesions in the chickens, and blood cholesterol was not significantly altered after treatment of chickens with DMBA, BaP, or TPA.
Abstract: Treatment of chickens for up to 20 wk with varying doses (0.1–10 mg/kg) of benzo[a]pyrene (BaP) or 7,12‐dimethylbenz[a]anthracene (DMBA) resulted in significant increases in incidence and size of atherosclerotic lesions at the two higher doses utilized (1 and 10 mg/kg). Maximal lesion formation for birds treated chronically with BaP occurred at 1 mg/kg, while development of lesions in birds treated with DMBA was roughly linear over the dose, range tested. The largest doses of BaP or DMBA (10 mg/kg for 20 wk) produced the highest percentage of chickens with detectable lesions (75 and 89%, respectively). Lower doses of BaP or DMBA resulted in a smaller percentage of birds (per group) with lesions, and the lowest dose (0.1 mg/kg) produced no statistical increase in lesion incidence. At approximately equimolar doses, DMBA appeared to be more potent than BaP in enhancing the development of lesions in the chickens. Administration of a single dose of BaP or DMBA followed by weekly doses of the tumor promoter 12‐...
TL;DR: In the 4-MPH-treated females and some AMPH-treated male mice, a few soft-tissue tumors were observed; however, their appearance could not be related to treatment.
Abstract: 4-Methylphenylhydrazine hydrochloride (4-MPH) was administered to randomly bred Swiss mice as 26 weekly sc injections of 140 microgram per gram of body weight and N'-acetyl-4-(hydroxymethyl)phenylhydrazine (AMPH) as 26 weekly sc injections of 500 microgram/g As a solvent control, physiological saline was also given as 26 weekly sc injections of 001 ml/g The 4-MPH treatment induced a significant incidence (24%) of fibrosarcomas in males In the 4-MPH-treated females and some AMPH-treated male mice, a few soft-tissue tumors were observed; however, their appearance could not be related to treatment 4-MPH is formed under special experimental conditions from 4-hydroxymethylphenyl-hydrazine, which is an in vitro breakdown product of agaritine, an ingredient of the cultivated mushroom Agaricus bisporus The implications of the findings are discussed
TL;DR: The tumorigenicity of the organochlorine pesticides appears to reflect an epigenetic mechanism, probably involving a promotional effect resulting from a disruption in intercellular communication.
Abstract: Genotoxicity was not elicited by any of a variety of organochlorine pesticides tested in the hepatocyte primary culture (HPC)/DNA repair assay utilizing hepatocytes from the rat, mouse, and hamster. DNA repair was observed in response to the positive control in all three systems. Thus the tumorigenicity of the organochlorine pesticides appears to reflect an epigenetic mechanism, probably involving a promotional effect resulting from a disruption in intercellular communication.
TL;DR: This study verifies that the unscheduled DNA synthesis seen in the hepatocyte primary culture/DNA repair test after carcinogen exposure in DNA repair and confirms the induction of DNA repair by pyrilamine maleate and tripelennamine HCl but not by methapyrilene.
Abstract: The autoradiographic unscheduled DNA synthesis measured in the hepatocyte primary culture/DNA repair test after exposure to chemical carcinogens was characterized. In order to document that this synthesis was occurring in nonreplicated DNA, density labeled, replicated DNA was separated from nonreplicated DNA by cesium chloride gradient centrifugation. Incorporation of [3H] thymidine into nonreplicated DNA was detected after exposure of hepatocytes to methyl methanesulfonate, an activation independent carcinogen, or N-2-acetylaminofluorene, an activation-dependent carcinogen, but not with fluorene, a noncarcinogen. N-4-Acetylaminofluorene, a mutagenic compound of uncertain carcinogenicity, also caused DNA repair. Both the autoradiographic assay and density gradient centrifugation detected incorporation of [3H] thymidine into DNA from the same hepatocyte preparation. By using density gradient centrifugation, DNA repair was detected in hepatocytes following exposure to the antihistamines pyrilamine maleate and tripelennamine HCl. Methapyrilene failed to elicit repair. Thus this study (1) verifies that the unscheduled DNA synthesis seen in the hepatocyte primary culture/DNA repair test after carcinogen exposure in DNA repair And (2) confirms the induction of DNA repair by pyrilamine maleate and tripelennamine HCl but not by methapyrilene.
TL;DR: The parameters measured in the chronic study are highly dependent on the age of the rat when Se-supplemented drinking water is initiated, including alkaline and acid phosphatase, SGOT, protein, glucose, and sialic acid.
Abstract: Acute and chronic effects of Se as sodium selenite given as a supplement in the drinking water of Sprague‐Dawley rats for 35 d, 1 yr, and 2 yr are compared. For the 35‐d study the experimental groups were untreated controls and rats supplemented with 1, 4, 8, 16, and 64 ppm Se. Survival was 100% in the control and 1 and 4 ppm groups, decreased in the 8 and 16 ppm groups, and was zero in the 64 ppm group. Body weights increased and were equivalent in the control and 1 and 4 ppm groups and substantially decreased in the 16 and 64 ppm groups. Serum alkaline phosphatase and glutamic‐oxaloacetic transaminase (SGOT) increased with 16 ppm Se and higher supplements. Se toxicity was apparent in microscopic pathology showing liver congestion, fatty degeneration of parenchymal cells, and necrosis. In the chronic studies untreated controls are compared with rats receiving 4 ppm Se in the drinking water. In general, the weight gains throughout were equivalent for both groups. The 1‐yr survival in each was above 90% an...
TL;DR: Thin-layer chromatography revealed both unmetabolized BaP and polar metabolites in the ovary, wolffian ducts, oocytes, and semen of English sole 24 h after ip injection with 200 microCi [3H]BaP.
Abstract: Accumulation of benzo[a]pyrene (BaP) by sexually mature flatfish gonad, its transfer to developing gametes, and its subsequent effects on developing embryos were studied. Thin-layer chromatography revealed both unmetabolized BaP and polar metabolites in the ovary, wolffian ducts, oocytes, and semen of English sole 24 h after ip injection with 200 microCi [3H]BaP. Concentrations of BaP and its metabolites were 3-11 times higher in oocytes and semen than in gonadal tissue. Fertilized eggs from flathead sole that had been fed 4.0 mg BaP 5 h before spawning demonstrated a significantly lower (p less than 0.001) hatching success (11.9%) than eggs from control fish (56.6%). Morphological abnormalities were found in only 1.6% of control embryos but in 5.6% of embryos from treated females.
TL;DR: Experimental findings indicate that any potential danger to the consumer is relative to the severity of the overall treatment of the fat, and a concerted effort should be made to minimize substantial accumulation of these in the authors' dietary fats.
Abstract: Heating of fats brings about measurable changes in their chemical and physical characteristics Heat is applied in processing for food manufacture, such as during hydrogenation of oils with a catalyst, and in frying for meal preparation Partially hydrogenated products generally contain substantial quantities of geometric and positional isomers of the original unsaturated fatty acids During deep‐fat frying, when the fat is used repeatedly, oxidative and thermal effects result in the formation of many volatile and nonvolatile products, some of which are potentially toxic, depending on the level of intake Because of concern about the types of changes that take place in fats during oxidative and thermal deterioration and the effects the derivatives could have on the consumer, many chemical and biological studies have been carried out Experimental findings indicate that any potential danger to the consumer is relative to the severity of the overall treatment of the fat In some studies we evaluated biologi
TL;DR: Exposure to vinyl halides at dose levels lower than those that elicit a significant increase in cancer incidence during the lifetime of the animal may, nonetheless, increase the risk of early death or moribundity from toxic pre- or subcarcinogenic effects.
Abstract: Carcinogenic and other toxic effects in rats and mice were examined during a 12‐mo period following exposure to vinyl chloride (VC) or vinylidene chloride (VDC). Exposure of male and female mice to 50, 250, or 1000 ppm VC for 6 h/d, 5 d/wk, for 1, 3, or 6 mo resulted in increased numbers of deaths and increased moribundity at all dose levels during the exposure and postexposure periods, as compared with air‐exposed controls. Similar observations were made with rats after 1, 3, 6, or 10 mo exposure to VC. Cumulative tumor incidence at various organ sites also increased in both species during the postexposure period in proportion to dose or duration of exposure at higher dose levels. However, except for mammary gland tumors in female mice, no significant increase in cumulative tumor incidence occurred in either species at 50 ppm VC or 55 ppm VDC, regardless of duration of exposure. These results suggest that exposure to vinyl halides at dose levels lower than those that elicit a significant increase in canc...
TL;DR: Results suggest that SCE induction is a common property of organophosphate insecticides, compared to two known genotoxicants, doxorubicin and ethyl methanesulfonate, which is much weaker.
Abstract: Induction of sister chromatid exchanges (SCEsj in cultures of Chinese hamster ovary cells by 10 anticholinesterase organophosphate insecticides was investigated. The insecticides were two phosphates (dichlorvos and dicrotophos), four sulfur‐containing organophosphates (malathion, parathion, leptophos, and diazinon), and four oxygen analogs of the latter (malaoxon, paraoxon, leptophosoxon, and diazoxonj. All of the compounds except diazinon induced statistically significant increases in SCE frequencies at concentrations between 0.03 and 1.0 mM. These results suggest that SCE induction is a common property of organophosphate insecticides. Compared to the sulfur‐containing organophosphates, the oxygen analogs consistently produced higher SCE frequencies and had stronger antiproliferative activity. Compared to two known genotoxicants, doxorubicin and ethyl methanesulfonate, the ability of organophosphates to produce SCEs is much weaker.
TL;DR: The results seemed to indicate the usefulness of the Salmonella/microsome test for detection of mutagens in human urine and suggest that people exposed to potentially carcinogenic chemicals may show high enough traces of those chemicals and their metabolites in their body fluids to be detected with current mutagenesis techniques.
Abstract: Urine samples from a control population and from a population of chemical workers from two chemical plants near Florence, Italy, were analyzed for the presence of mutagenic chemicals by the Salmonella/microsome test. When tested with strain TA 1538, the urine of nonsmoking chemical workers showed higher mutagenic activity than that of controls in the presence of in vitro metabolic activation, but no difference was found between controls and chemical workers who both smoked. Increased mutagenic activity was observed in the group of control smokers compared to control nonsmokers, but the same effect was not observed for chemical workers. When TA 100 was used as the tester strain, the chemical workers, both smoking and nonsmoking, had significantly higher mutagenic activity than controls. The mutagenic activity fell to control levels in some workers’ urine after 20 d leave. Although some perturbing effects of smoking habits were observed, the results seemed to indicate the usefulness of the Salmonella/ micro...
TL;DR: The reported values are representative of the levels of persistent organochlorine pesticides and pesticide metabolites found in 1978 in white female residents of Dade County, Florida.
Abstract: Previously published analytical procedures by which drinking water, human blood serum, and adipose tissue may be analyzed for trace amounts of organochlorine pesticides have been modified to permit use of smaller samples. Data on percent recovery, detector sensitivity, and limit of detectability have been collected for each of the three reported procedures. The methodology has been applied to 59 blood samples, 20 drinking water samples, and 10 necropsy adipose tissue samples. Only hexachlorobenzene and dieldrin were detected in water. Hexachlorobenzene, beta-hexachlorocyclohexane, dieldrin, p,p'DDE, and p,p'DDT were present in blood. No heptachlor, heptachlor epoxide, oxychlordane, trans-nonachlor, or o,p'-DDT was found. In.fat, the compounds present in blood plus oxychlordane, heptachlor epoxide, and trans-nonachlor were detected. No heptachlor, aldrin, o,p'-DDT, or alpha- or gamma-chlordane was present. The reported values are representative of the levels of persistent organochlorine pesticides and pesticide metabolites found in 1978 in white female residents of Dade County, Florida.
TL;DR: Data indicate little risk to normal subjects from excessive aspartate or phenylalanine levels after ingestion of single abuse loads of aspartame, which are considerably above the normal postprandial range and below values associated with toxic findings.
Abstract: Plasma and erythrocyte concentrations of amino acids were measured in 18 fasting adult subjects (9 male, 9 female) administered abuse doses of aspartame (100, 150, and 200 mg/kg body weight) dissolved in 500 ml orange juice. Six subjects were studied at each dose. Plasma aspartate concentrations increased significantly (p less than or equal to 0.05) over baseline values after ingestion of each dose. However, the increase was small in each case, and maximal levels observed were below those noted postprandially in formula-fed infants. No significant changes (p greater than 0.05) were noted in erythrocyte glutamate, or erythrocyte aspartate concentrations after any dose. Plasma phenylalanine concentrations increased significantly over fasting concentrations (p less than 0.01) from 15 min to 6 h after each dose, and the increase was proportional to dose. Mean (+/- SD) peak plasma phenylalanine concentrations were 20.3 +/- 2.03, 35.1 +/- 11.3, and 48.7 +/- 15.5 mumol/dl, respectively, after aspartame doses of 100, 150, and 200 mg/kg. Erythrocyte phenylalanine concentrations showed similar changes. Although these phenylalanine concentrations are considerably above the normal postprandial range (12 +/- 3 mumol/dl), they are below values associated with toxic findings. These data indicate little risk to normal subjects from excessive aspartate or phenylalanine levels after ingestion of single abuse loads of aspartame.
TL;DR: Measurement of neurotoxic esterase correctly predicted the lack of potential of the two flame retardants to induce delayed neurotoxicity in hens.
Abstract: Delayed neurotoxicity in hens was reported after the administration of several chlorinated alkyl phosphates. Neurotoxicity increased in a homologous series with the size and/ or hydrophobic nature of substituents. In the present study the neurotoxicities of two commercial flame retardants, Fyrol PCF [tri(2‐chloropropyl) phosphate] and Fyrol CEF [tri(s‐chloroethyl) phosphate], were compared in adult White Leghorn hens. When Fyrol PCF (10 ml/kg neat) was administered orally to four hens, no inhibition of plasma cholinesterase or brain neurotoxic esterase was evident 24 h later. Fyrol CEF (10 ml/kg neat) produced significantly greater inhibition of plasma cholinesterase (87.1%) and brain neurotoxic esterase (30.0%). Since neither compound produced >75% neurotoxic esterase inhibition, they were not expected to produce delayed neurotoxicity in hens. This was verified in hens treated twice with Fyrol PCF (10 ml/Mg neat) or Fyrol CEF (10 ml/kg neat) and observed for 6 wk. Neither group showed behavioral or histo...