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PubMed1986

Metabolism and disposition of ortho-benzyl-para-chlorophenol in male rats.

The metabolism and disposition of ortho-benzyl-para-chlorophenol (BCP) has been investigated in the male rat following an oral dose of 69 mg/kg or 206 mg/kg. BCP was rapidly eliminated at both dose levels with 45-49% of the dose appearing in the urine and 44-49% in the feces during the 5-d period after dosing. After 5 d only 0.28-0.3% of the dose remained in the body, with almost half this value accounted for in the liver and kidney. The dynamics for the overall elimination of radioactivity from the body was biphasic at both dose levels. The initial rapid alpha phase had a well defined half-life of 8-9 h, and the slower beta phase had an estimated half-life of approximately 52-140 h. Analysis of the 12-24-h urine indicated that a majority of the radioactivity (41-61%) was present as sulfate and/or glucuronide conjugates. Treatment with purified aryl sulfatase suggested that sulfate esters were the predominate conjugate. Gas chromatography-mass spectroscopy (GC/MS) of the products isolated after enzymatic hydrolysis of the conjugates and purification by thin-layer chromatography (TLC) identified BCP, as well as two metabolites in which the benzyl ring was modified. One metabolite contained a hydroxyl substituent on the benzyl ring, and the other contained a hydroxyl and a methoxyl substituent. Preliminary analysis of the 12-24-h feces demonstrated the presence of BCP and two other components with chromatographic properties identical to the metabolites identified in the urine. A metabolic pathway for BCP has been proposed to account for the observed metabolites.

Animals↗
PubMed1986

Disposition of o-benzyl-p-chlorophenol in male rats.

The disposition and metabolism of o-benzyl-p-chlorophenol (BCP) were studied in male Fischer-344 rats. Three days after oral administration of [14C]BCP at 10, 100, or 1000 mg/kg, more than 90% of each dose was excreted in urine and feces. Comparison of disposition after intravenous, dermal, or oral administration indicated that BCP was not completely absorbed from the gastrointestinal tract or skin. Biliary excretion of BCP was dose-dependent, with proportionally less BCP-derived radioactivity being excreted in the bile as the dose was raised. The results also indicated that enterohepatic circulation was involved in BCP disposition. The major in vivo metabolites were glucuronyl conjugates of BCP and hydroxy-BCP. Glutathione conjugates were also present in urine. In vitro metabolism studies support the observation that microsomal oxidation and glutathione and glucuronyl conjugation play major roles in BCP metabolism. Spleen, kidney, and liver contained the highest tissue concentrations of BCP-derived radioactivity. The presence of more nonextractable BCP-derived radioactivity in kidney than in liver is compatible with the hypothesis that covalent binding of BCP to renal tissue may be associated with BCP-induced nephrotoxicity.

Administration, Oral↗
PubMed2005

By-side chlorodibenzo-P-dioxins and chlorodibenzofurans in technical chlorobiphenyl formulations of aroclor 1268, chlorofen, and clophen T 64.

Aroclor 1268, Chlorofen, and Clophen T 64 technical chlorobiphenyl formulations were examined for 75 congeners of chlorodibenzo-p-dioxin (CDD) and 135 congeners of chlorodibenzofuran (CDF) using isotope dilution technique, separation, and enrichment on silica gel impregnated with activated carbon and final high resolution gas chromatography (HRGC)/high resolution mass spectrometry (HRMS) quantification. Three the most highly chlorinated congeners of CDD were found in Aroclor 1268, Chlorofen, and Clophen T 64. In the case of CDF, the number of congeners identified was 108 with 44 coeluting in pairs and 3 in triplicate in Aroclor 1268, 16 with 4 coeluting in pairs in Chlorofen, and 88 with 46 coeluting in pairs and 3 in triplicate in Clophen T 64. The total CDD and CDF concentrations of Aroclor 1268, Chlorofen, and Clophen T 64 were 24, 160, and 8.5 ng/g and 1600,270,000, and 4000 ng/g, respectively. No mono- to hexa-CDDs could be quantified in Aroclor 1268 (<0.03 to <1 ng/g), Chlorofen (<0.07 to <0.3 ng/g), or Clophen T 64 (<0.007 to <2 ng/g), whereas two hepta-CDDs and octa-CDD were found in all three formulations, and Chlorofen was richer in those compounds, followed by Aroclor 1268 and Clophen T 64.

Aroclors↗
PubMed2002

Bayesian methods for a three-state model for rodent carcinogenicity studies.

The objective of a chronic rodent bioassay is to assess the impact of a chemical compound on the development of tumors. However, most tumor types are not observable prior to necropsy, making direct estimation of the tumor incidence rate problematic. In such cases, estimation can proceed only if the study incorporates multiple interim sacrifices or we make use of simplified parametric or nonparametric models. In addition, it is widely accepted that other factors, such as weight, can be related to both dose level and tumor onset, confounding the association of interest. However, there is not typically enough information in the current study to assess such effects. The addition of historical data can help alleviate this problem. In this article, we propose a novel Bayesian semiparametric model for the analysis of data from rodent carcinogenicity studies. We develop informative prior distributions for covariate effects through the use of historical control data and outline a Gibbs sampling scheme. We implement the model by analyzing data from a National Toxicology Program chronic rodent bioassay.

Animals↗
PubMed1993

Adaptation of Pseudomonas aeruginosa to 2,2'-methylenebis (4-chlorophenol).

A culture of Pseudomonas aeruginosa, isolated from a cooling water system, was grown in the presence of sub-inhibitory concentrations of 2,2'-methylenebis(4-chlorophenol) (MBC). It adapted to increasing concentrations from an initial minimum inhibitory concentration of 36 micrograms ml-1 to the highest, 80 micrograms ml-1. Resistant cultures exhibited a higher survival rate when exposed to 320 micrograms ml-1 than did the original strain. Lipopolysaccharide and outer membrane protein profiles were determined by SDS PAGE. No changes were detected in lipopolysaccharide profiles. The quantity of OprP, the phosphate uptake protein in the outer membrane, decreased to a low level correlating with decreased phosphate (P(i)) uptake during growth. It is proposed that OprP is the place of entry for MBC and that the cell can adapt by decreasing the level of OprP in the outer membrane.

Adaptation, Physiological↗
PubMed1979

A comparison of the antibacterial properties of some udder creams and ointments.

The antibacterial activity of three udder creams and two ointments was assayed using three different methods. Seven different bacterial genera were used as test organisms providing a total of 17 strains. Only a single strain of corynebacterium was inhibited by all the preparations. Certain strains of staphylococci and streptococci were inhibited by four of the preparations. The gram-negative organisms showed greatest resistance to the antibacterial agents tested. The in vitro assays showed only one of the five preparations to have even slight bactericidal activity. These preparations when tested on the teats of dry and lactating cows showed similar results to the in vitro experiments.

Animals↗
PubMed1991

Contact hypersensitivity response to o-benzyl-p-chlorophenol in mice.

o-Benzyl-p-chlorophenol was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 1.0, 3.0, and 10.0% o-benzyl-p-chlorophenol and challenged with 20.0% o-benzyl-p-chlorophenol. Doses of o-benzyl-p-chlorophenol were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of Freund's complete adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling test one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity response to o-benzyl-p-chlorophenol with or without adjuvant pretreatment.

Animals↗
PubMed1975

[Committee on anthelmintics. Residual group].

A number of the older and a few recent anthelmintics are enumerated or briefly discussed. Moreover some attention is paid to anthelmintics, used for nematodes and trematodes which have a limited effect on cestodes.

Animals↗