Biomedical subjects

F B Daniel

Publications and source records attributed to F B Daniel.

78 records · Page 5Linked to original sources

PubMedDate not supplied

The effects of subacute and subchronic oral exposure to cis-1,2-dichloroethylene in Sprague-Dawley rats.

Cis-1,2-dichloroethylene was administered daily by corn oil gavage to male and female Sprague-Dawley rats at the following dose levels: 1.0, 3.0, 10.0 and 22.0 mmol/kg/day for 14 days. Doses gavaged during the 90-day subchronic study were 0.33, 1.00, 3.00 and 9.00 mmol/kg/day. There were no compound-related deaths or histopathological changes demonstrated. Significant increases in relative liver weights were seen after 14- and 90-days of treatment in both sexes. This study demonstrates some indication of toxicity at subacute and subchronic exposure levels as low as 0.33 mmol/kg/day. Implications of liver abnormalities were demonstrated at an exposure level of 1 mmol/kg/day while kidney abnormalities (relative weights) were demonstrated at an exposure level of 0.33 mmol/kg/day.

Administration, Oral↗

PubMedDate not supplied

The effects of subchronic chlorate exposure in Sprague-Dawley rats.

Male and female Sprague-Dawley rats were exposed to drinking water containing 3.0, 12.0 or 48.0 mM sodium chlorate. The mean drinking water consumption varied between exposure groups from 100-200 ml/kg/day. Female exposure groups consistently drank more water (23-42%) than male exposure groups thereby receiving more chlorate/kg/day at every exposure level. There were no compound related deaths; however, both males and females in the high exposure groups had significant weight loss during the 90-day exposure period. Also, in these same groups females had mild but significant decreases in the following relative organ weights; adrenals, thymus and spleen, while the relative brain weight was increased. In males, the heart, kidneys and liver were mildly decreased while the brain and testes were mildly increased. Red blood cell counts and percent hematocrit were decreased in both sexes in the high dose group. Pituitary gland (pars distalis) vacuolization and thyroid gland colloid depletion were prominent in both sexes in mid and/or high dose animals. A NOAEL of 0.36 mM chlorate/kg b.w./day in males and 0.50 mM chlorate/kg b.w./day in females were established.

Animals↗

PubMedDate not supplied

Toxicity studies of 1,3-dichlorobenzene in Sprague-Dawley rats.

Male and female Sprague-Dawley rats received 1,3-dichlorobenzene daily by corn oil gavage for 10 or 90 consecutive days. The 10-day study doses were 0, 37, 147, 368 and 735 mg/kg; the 90-day study doses were 0, 9, 37, 147 and 588 mg/kg. In the 10-day study, there was a significant depression of body weight in both sexes at 735 mg/kg. Liver weights were significantly increased in both sexes at 368 and 735 mg/kg. Serum cholesterol levels were significantly elevated in both sexes at 368 and 735 mg/kg. Histopathological evaluation revealed centrolobular hepatocellular degeneration at 368 mg/kg in males and 735 mg/kg in females. In the 90-day study, body weights were significantly depressed in both sexes at 588 mg/kg. Normalization of food and water consumption by final body weight indicated that at 588 mg/kg both sexes had increased food and water consumption relative to controls. Absolute and relative liver weights were significantly increased in both sexes at 147 and 588 mg/kg. Relative kidney weights were significantly higher in both sexes at 588 mg/kg and in males at 147 mg/kg. Serum cholesterol and calcium levels were significantly elevated over controls in females at 37, 147, and 588 mg/kg, and in males at all dose levels. Histopathological evaluation at 147 and/or 588 mg/kg demonstrated liver and thyroid lesions in both sexes, and pituitary and kidney lesions in males. A NOAEL was not firmly established.

Administration, Oral↗

PubMedDate not supplied

Site-specific modulation of carcinogen-induced gastrointestinal tract nuclear anomalies in B6C3F1 mice by chloroform.

Chloroform (CHCl3) is an established rodent carcinogen and a prevalent contaminant of chlorine-disinfected drinking water. Thus in the United States CHCl3, along with other trihalomethanes, is regulated not to exceed 100 ppb in potable water. Recently, several studies have shown that CHCl3 also has anti-cancer properties as it inhibits tumor growth in mouse liver and in the gastrointestinal tract of the rat. In this paper we show that CHCl3 also inhibits the propensity for three gastrointestinal tract carcinogens, benzo(a)pyrene (BAP), 1,2-dimethylhydrazine (DMH) and methylnitrosourea (MNU), to induce nuclear anomalies in the proximal colon of the B6C3F1 mouse. For example, in mice pre-adapted to 1800 ppm CHCl3 for 30 days prior to the carcinogen administration the level of nuclear anomalies induced in the proximal colon by BAP was reduced by four-fold (0.9 +/- 0.7 v. 3.6 +/- 1.0 anomalies/10 crypts; p less than 0.001) and two-fold for MNU (2.4 +/- 1.0 v. 4.6 +/- 1.6; p less than 0.001) and DMH (0.9 +/- 0.9 v. 1.7 +/- 0.8; p = 0.03). In the duodenum CHCl3 was effective at inhibiting unclear anomalies only for MNU (45.3 +/- 4.6 v. 30.4 +/- 3.5; p = 0.02). The inhibitory effect of CHCl3 does not extend to nuclear anomalies of the forestomach. The anti-cancer properties of CHCl3 are discussed in light of its cancer causing potential and possible application to human risk assessment.

1,2-Dimethylhydrazine↗

PubMedDate not supplied

Oxidative metabolites of 7,12-dimethylbenz[a]anthracene. Further investigation of the K-region epoxide.

Metabolism of 7,12-dimethylbenz[a]anthracene in rat liver 10,000 g supernatant fraction has been examined by combined gas chromatography-mass spectrometry subsequent to high-pressure liquid-chromatographic separation of the incubation mixture. In addition to the mono-, di-, and trihydroxylated oxidative metabolites usually associated with the biotransformation of polycyclic aromatic hydrocarbons, we observed the formation of a methanolysis product from the K-region epoxide intermediate during the workup procedure. The identification of this compound provides a direct evidence for the presence of the K-region epoxide in the metabolism mixture, and it serves as a convenient means to assay for this metabolite. Moreover, we detected the methanolysis derivative only from the K-region epoxide but none from the non-K-region counterparts. This finding suggests that the non-K-region epoxides undergo facile enzymatic and nonenzymatic hydrolysis and/or rearrangement reactions as soon as they are produced. On the other hand, the K-region epoxide possesses greater stability. It can remain longer in a metabolism mixture and react with methanol subsequently.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Metabolism of 7,12-dimethylbenz(a)anthracene. Correlation of dihydrodiol and phenol metabolites with organ susceptibility to carcinogenesis in Sprague-Dawley and long-Evans rats.

The biotransformation of DMBA in uninduced and induced 10,000g organ supernatants derived from female Sprague-Dawley and Long-Evans rats, which are respectively sensitive and resistant to DMBA-induced carcinogenesis, was studied. Qualitative and quantitative differences in the metabolism of DMBA are summarized as a function of organ (liver, lung, kidney, and mammary) and strain and oxidative enzyme induction protocol utilized and are attributed to the differential induction of various cytochrome P-450s. The percent production of 7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol (DMBA-3,4-DHD) and phenol metabolites in 10,000g organ supernatants from beta-napthoflavone induced animals correlated with organ susceptibility to DMBA-induced carcinogenesis in both SD and LE rat strains. A negative correlation was observed between 8,9-DHD production and reported sensitivity to specific organ tumorigenesis, but no other relationship was observed with other metabolites (7- and 12-hydroxymethyl, K-region DHD, and 10,11-DHDs). Similar DMBA metabolite hplc profiles were observed in the same organ S-10 fractions isolated from either SD or LE rats. Thus, the organotropic, but not the strain, selectivity of DMBA-induced carcinogenicity appears to be attributed in part to metabolic activation.

9,10-Dimethyl-1,2-benzanthracene↗