Charles H. Hine

The rates of radical formation from the dipyridylium herbicides paraquat, diquat, and morfamquat in homogenates of rat lung, kidney, and liver: An inhibitory effect of carbon monoxide

Abstract In an attempt to elucidate the mechanism of toxicity in mammals and to explain some organ specificities observed in chronic dipyridylium herbicide intoxication, the specific rates of radical cation appearance for paraquat, diquat, and morfamquat were measured in homogenates of rat lung, kidney, and liver. In each organ homogenate, the order of the rates was morfamquat > diquat > paraquat. For each herbicide the order of the rates was liver > lung > kidney. The results are inconsistent with the hypothesis that selectively enhanced rates of radical production in the target organs are responsible for the specificities observed. Carbon monoxide inhibited the rate of appearance of the diquat radical in all three organ homogenates: in contrast, the rate of radical formation from paraquat and morfamquat were not affected. No inhibition was observed in any combination of organ and herbicide by either potassium cyanide or SKF 525-A. It is concluded that diquat is reduced by a different electron transferring agent than either paraquat or morfamquat.

Mutagenic action of a series of epoxides

The mutagenicity of a series of 13 epoxide compounds was studied using a bacterial plate assay system. The histidine-dependent tester strains TA98 (for frameshift mutagens) and TA100 (for base-pair substitution mutagens) of Salmonella typhimurium were used. Mutagenicity was evaluated both with and without the additon of rat liver microsomal extract. Dieldrin, diglycidyl ether of bis phenol A and 3 of its homologues were not mutagenic. Allyl glycidyl ether, n-butyl glycidyl ether, vinly cyclohexene diepoxide, glycidol, glycidal-dehyde, diglycidyl ether, diepoxybutane and diglycidyl ether of substituted glycerine were mutagenic in the TA100 strain, causing reversion of the bacteria to histidine independence. Dose-reponse curves of the mutagenicity of the latter 4 compounds were obtained. On a molar basis, glycidaldehyde was about 20-50 times more potent in producing mutation that were the other 3 epoxides in the dose-response test. In general, the mutagenicity of the epoxides was not enhanced or diminished by the addition of microsomal extract.

Effects of Various Metals on Behavior of Conditioned Goldfish

A conditional avoidance technique was utilized to assess the deleterious effect of four metal ions in the aquatic environment of fish. All test ions, arsenic, lead, mercury, and selenium impaired performance at concentrations below the lethal concentration for 1% (LC1). Mercury was the most potent, producing measurable effects at 0.Q03 ppm. Behavioral toxicity techniques are suggested as useful in setting water quality standards.

The mutagenic potential of ethylene oxide using the dominant-lethal assay in rats

Abstract The mutagenicity of ethylene oxide in mammalian germinal cell lines was investigated using the dominant-lethal test in rats. Male rats were exposed to 1000 ppm of ethylene oxide for 4 hr and mated each week to groups of two females for 10 weeks. A significant increase in postimplantational fetal deaths was noted in the test group when compared to the negative control group. This significant increase was noted only during the first 5 weeks of the experiment, corresponding to the residence time of germinal cells exposed to ethylene oxide after their meiotic division. Triethylenemelamine served as the positive control. These results indicate that ethylene oxide is capable of inducing mutagenic changes in rat germinal cells.

Mutagenicity of halogenated and oxygenated three-carbon compounds.

Four structurally related three-carbon compounds, known for their antifertility activity in the male, and the brominated derivatives of two of these compounds were tested for mutagenic activity by the Salmonella typhimurium test of Ames et al. In the presence of strain TA-100, a base-pair substituion detector strain, 1,2-dibromo-3-chloropropane (DBCP), was the most active compound tested but required enzymatic conversion by 59 microsomal preparation to an active mutagen. Three of these compounds containing an epoxide group-epichlorohydrin, epibromohydrin, and glycidol-were highly active direct mutagens, not requiring 59 for activation, alpha-Chlorohydrin was the least active compound tested; alpha-bromohydrin was 40 times more active than its chlorinated analog. Epibromohydrin was only slightly more active than epichlorohydrin, but both were highly active. With both of the halogenated epoxides, 59 preparation caused a substantial decrease in mutagenic activity at every concentration tested. All six compounds showed dose-related responsiveness for the base-pair substitution detector strains used. However, they were relatively inactive against the frameshift detector strain of S. typhimurium, TA-98. Glycerol, propylene glycol, and n-propanol, which are also three-carbon compounds containing one or more hydroxy groups, were inactive when trested at high concentrations with strain TA-100.

Pulmonary changes in animals exposed to nitrogen dioxide, effects of acute exposures

Abstract The comparative toxicity of NO 2 was studied in five species: mice, rats, guinea pigs, rabbits, and dogs. Fifty parts per million was a critical concentration; below this value mortality rarely occurred with exposures up to 8 hours. A study was made of the sequential development of pathologic changes in the lung with grading of edema, congestion, interstitial irritation, bronchiolitis, and interstitial fibrosis. Acute deaths were characterized by marked bronchiolitis, desquamated bronchial epithelium, infiltration by polymorphonuclear cells, and edema fluid in the alveoli. Interstitial fibrosis occurred in about one-third of the surviving animals at 30 days and persisted in some for periods up to 6 months. Stress induced by exercise following exposure, by adrenalectomy, or by high levels of CO 2 increased mortalities. Toxic responses were separated into four clinical and pathologic entities: acute asphyxia secondary to laryngeal edema and spasm; acute pulmonary lung edema; bronchiolitis and pneumonia; and permanent, nonincapacitating residua in the lung.

Retention of lead in the rat

This study compares the relative effectiveness of different diets, therapeutic agents, and chelation in reducing the elevated tissue concentrations of lead in rats. Young male rats were given lead by exposure to drinking water containing 350 ppm of lead as lead acetate. After four weeks of exposure, the source of lead was removed, surviving rats randomized among eight groups, and subjected to one of the following: (1) terminated (positive control-1); (2) returned to the previous exposure to lead (positive control-2); (3) given the control diet (positive control-3); (4) increased minerals (diet); (5) increased ascorbic acid (diet) and thiamine (injection); (6) increased cellulose (diet); (7) ethylenediaminetetraacetic acid (EDTA) (injection); and (8) dimercaptosuccinic acid (DMSA) (injection). After six weeks, the experiment was terminated, the following tissues were harvested, and the lead concentrations determined: blood, brain, calvaria (flat bone), femur (long bone), kidney, and liver. Histopathological examinations of kidneys were provided, and the hematocrit and hemoglobin were measured. The highest lead concentrations were found in the femurs of rats following ten weeks exposure. All groups receiving lead had significantly higher lead concentrations than the controls. None of the diets produced a significant reduction in the concentration of lead in the tissues when compared with the positive control-3 (the leaded rats not receiving treatment). A reduction in the lead concentration in the brain and liver was obtained by chelation.

Blood and Urine Concentrations of Subjects Receiving Barbiturates, Meprobamate, Glutethimide, or Diphenylhydantoin

(1970). Blood and Urine Concentrations of Subjects Receiving Barbiturates, Meprobamate, Glutethimide, or Diphenylhydantoin. Clinical Toxicology: Vol. 3, No. 1, pp. 131-145.

Assessment of the mutagenic properties of diquat and paraquat in the murine dominant lethal test

Summary The mutagenic potentials of 1,1′-ethylene-2,2′-bipyridylium (diquat) and 1,1′-dimethyl-4,4′-bipyridylium (paraquat) were assessed in fertile male mice with the dominant lethal test. No mutagenic effects on any maturation stage of spermatogenesis in treated males were detected, i.e. , there was no significant increase in the rates of postimplantational early fetal deaths or preimplantational egg losses in females mated with the treated males. However, both chemicals induced an antifertility effect detected as significantly reduced pregnancy rates. The antifertility effect of paraquat treatment was restricted to postmeiotic late spermatids, while with diquat treatment all postmeiotic maturation stages and also premeiotic early and late spermatocytes were affected.

Blood Codeine Concentrations in Fatalities Associated with Codeine

The toxicologic findings in eight cases of death due primarily to codeine overdosage are presented. Blood codeine concentrations ranged from 1.4 to 5.6 mug/ml as determined by gas-liquid chromatography. Morphine was found in only two of the blood samples, at concentrations of 0.2 and 0.6 mug/ml, and may have resulted from heroin usage rather than codeine metabolism. A case of death of a codeine user by violent means is also presented in which the blood codeine concentration was 2.6 mug/ml.