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J de Jongh

Publications and source records attributed to J de Jongh.

6 recordsLinked to original sources
PubMed1996

Biokinetics and biokinetic models in risk assessment.

Risk assessment of xenobiotics using animal data involves extrapolation from high doses to low ones, and from animal species to humans. In some cases it also involves extrapolation from one route of exposure to another. To assess the risk of exposure to xenobiotics, information on both biokinetics and biodynamics are needed. The contribution of biokinetics to risk assessment is the subject of this review. The review includes the general aspects of biokinetics of chemicals, the models available to describe the biokinetic behaviour of a chemical and a discussion of the class of biokinetic models that is considered most suited for application to risk assessment: the physiologically-based biokinetic (PBBK) models. The power of PBBK models is illustrated with a few examples.

Administration, Cutaneous↗
PubMed1993

Toxicokinetic interactions between chlorinated aromatic hydrocarbons in the liver of the C57BL/6J mouse: I. Polychlorinated biphenyls (PCBs).

2,2',4,4',5,5'- (PCB 153), 2,3,3',4,4',5- (PCB 156) and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) were administered orally to three groups of C57BL/6J mice using single doses of 1.5-109.1 mg/kg. Two other groups of mice received binary mixtures of PCB 153 and 156 or PCB 153 and 169. The hepatic deposition, elimination, CYP1a and CYP2b dependent enzyme activities were studied during a 77-day period. Some interactive effects on hepatic deposition and elimination were observed, resulting in increased deposition and faster elimination. These effects were most pronounced for the PCBs 156 and 169. A potentiating effect on hepatic CYP1a dependent 7-ethoxyresorufin-O- deethylation (EROD) activity was observed for the combination of PCB 156 and 153. Based on the results from the present study and earlier studies, it is suggested that the potentiating effect on EROD activity might be caused by a mechanism that is governed by at least two factors. The first is a toxicokinetic modulation of hepatic retention. The second factor is probably an elevation of hepatic Ah receptor levels by PCB 153.

Animals↗
PubMed1989

Disposition and elimination of three polychlorinated dibenzofurans in the liver of the rat.

The disposition and elimination of 1,2,3,6,7,8-HxCDF (HxCDF), 1,2,3,7,8-PnCDF (1-PnCDF), and 2,3,4,7,8-PnCDF (4-PnCDF) were studied in liver of female Sprague-Dawley rats after administration of a single oral dose of 3.5-6.3 micrograms/kg. The disposition of these PCDF congeners was structure and vehicle dependent. Administration in peanut oil caused the highest liver retention, compared with administration through the standard diet. Half-lives in liver for 1-PnCDF, 4-PnCDF, and HxCDF were 3.3, 108, and 73 days, respectively. 4-PnCDF showed very high liver retention: greater than or equal to 70% of the dose in the first days after administration. To study kinetic interaction in the liver, mixtures of 1-PnCDF and 4-PnCDF (Experiment I) and of 4-PnCDF and HxCDF (Experiment II) were administered. The presence of 4-PnCDF in Experiment I did not significantly influence the half-life of 1-PnCDF. In Experiment II the estimated half-life of 4-PnCDF was again 108 days, but for HxCDF an increased half-life was found, 156 days. It is concluded that PCDFs with a chlorine substituent(s) adjacent to the oxygen bridge (4- and 6-positions) are eliminated very slowly with t1/2 much greater than that of TCDD.

Animals↗
PubMedDate not supplied

Toxicokinetics of an environmentally relevant mixture of dioxin-like PHAHs with or without a non-dioxin-like PCB in a semi-chronic exposure study in female Sprague Dawley rats.

Female Sprague Dawley rats were treated subcutaneously for 20 weeks with an environmentally relevant mixture of dioxin-like PHAHs with (PHAH+) or without (PHAH-) 2,2',4,4',5,5'-hexachlorobiphenyl. The hepatic retention (% of given dose) of the various PHAH congeners differed considerably and in the following order: 2,3,4,7,8-pentachlorodibenzofuran (30.5-43.1%), 3,3',4,4',5-pentachlorobiphenyl (12.8-17.6%), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (6.9-10.8%), 2,3,7,8-tetrachlorodibenzo-p-dioxin (3.2-4.5%), 2,3,3',4,4',5-hexachlorobiphenyl (1.0-1.7%), 2,2',4,4',5,5'-hexachlorobiphenyl (0.5-0.8%) and 2,3',4,4',5-pentachlorobiphenyl (0.2-0.4%). A decrease of the hepatic retention of 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF was found at increasing doses of the PHAH+ mixture. 2,2',4,4',5,5'-Hexachlorobiphenyl increased the hepatic retention (1.3-2 times) of all congeners in the PHAH+ group, compared to the TEQ equivalent dosed PHAH- group. No interactions were observed on the ethoxyresorufin-O-deethylase activity.

Animals↗