A review of the bioavailability of petroleum constituents

Exposure to petroleum constituents at contaminated sites may occur through a variety of pathways, including inhalation of vapors and particulates, ingestion of water and soils, and dermal contact with water and soils. Accurately assessing the human health risks from such exposures requires information on the medium‐ and route‐specific bioavailability of petroleum constituents (e.g., how well these chemicals enter the body via the gastrointestinal tract and skin). For example, when the medium or exposure route in an animal toxicity assay (e.g., ingestion of water) differs from the actual route of human exposure at the petroleum contaminated site (e.g., dermal contact with soil), adjustments should be made that reflect the relative bioavailability of the chemical in the different media. The focus of this article is on (1) the availability of oral and dermal absorption data for one PAH (benzo[a]pyrene, (B[a]P) and three VOCs in soil (benzene, toluene, and xylene); (2) factors affecting the uptake of these PAHs and VOCs from soil; and (3) ways to incorporate bioavailability data into human health risk assessments. Based on our review, we recommend the following default values for the oral and dermal absorption of B[a]P, benzene, toluene, and xylene from soil:

A review of the bioavailability of petroleum constituents

All authors

Jennifer Bramard & Barbara D. Beck

https://doi.org/10.1080/15320389209383417

Published online:

02 December 2008

Display Table

Site‐specific information such as chemical concentrations in soil, soil characteristics, soil loadings on the skin, contact site, and contact time could result in modifications of these numbers. As shown, our default absorption values are generally less than those recommended by the U.S. EPA (1991a,b,c). The implications of these estimates of bioavailability for risk assessment and for the selection of soil cleanup levels at petroleum‐contaminated sites are discussed.     

The steroid antagonist RU38486 is metabolized by the liver microsomal P450 mono-oxygenases

Microsomal preparations from adult male rat liver actively oxidized RU38486 into the 11 beta-monodemethylated, 11 beta-didemethylated and 17 alpha-hydroxylated derivatives, metabolites which are known to be formed in vivo. These oxidative reactions were inhibited at different degrees by P450 chemical inhibitors. Pretreatment of the animals by P450 mono-oxygenase prototype inducers led to drastic changes in RU38486 metabolization. Methylcholanthrene treatment carried out a significant decrease while phenobarbital markedly increased the metabolic activity of the liver microsomes. Moreover, antibodies to methylcholantrene-inducible P450 forms did not affect the metabolic activity while a complete blockade-of RU38486 oxidation was observed in the presence of antibodies to phenobarbital- inducible forms. The present results demonstrate that liver P450 mono-oxygenases are engaged in different oxidative steps of RU38486 metabolism and that phenobarbital-inducible but not methylcholanthrene-inducible P450 forms are active in RU38486 degradation.     

NADPH-cytochrome P-450 oxidoreductase gene organization correlates with structural domains of the protein

cDNA clones to rat liver NADPH-cytochrome P-450 oxidoreductase were used to isolate genomic clones from a Wistar-Furth inbred rat genomic DNA library. Fifteen exons containing the coding region and 3'-nontranslated segment of the P-450 reductase gene were identified, spanning 20 kilobases of DNA contained in 3 lambda-Charon 35 clones. The organization of this single copy gene reveals a general correspondence between exons and structural domains of the protein, with the segment responsible for anchoring the reductase to the microsomal membrane and several segments involved in FMN, FAD, and NADPH binding encoded by discrete exons.     

Decreased nuclear matrix DNA topoisomerase II in human leukemia cells resistant to VM-26 and m-AMSA

CEM leukemia cells selected for resistance to VM-26 (CEM/VM-1) are cross-resistant to various other DNA topoisomerase II inhibitors but not to Vinca alkaloids. Since DNA topoisomerase II is a major protein of the nuclear matrix, we asked if alterations in nuclear matrix topoisomerase II might be important in this form of multidrug resistance. Pretreatment of drug-sensitive CEM cells for 2 h with either 5 microM VM-26 or 3 microM m-AMSA reduced the specific activity of newly replicated DNA on the nuclear matrix by 75 and 50%, respectively, relative to that of the bulk DNA. However, neither VM-26 nor m-AMSA affected the relative specific activity of nascent DNA isolated from the nuclear matrices of drug-resistant CEM/VM-1 cells. The decatenating and unknotting activities of DNA topoisomerase II were 6- and 7-fold lower, respectively, in the nuclear matrix preparations from the CEM/VM-1 cells compared to parental CEM cells. Western blot analysis revealed that the amount of immunoreactive topoisomerase II in the nuclear matrices of the CEM/VM-1 cells was decreased 3.2-fold relative to that in CEM cells, but there was no significant difference in the amount of enzyme present in the nonmatrix (1.5 M salt soluble) fractions of nuclei from these cell lines. Increasing the NaCl concentration used in the matrix isolation procedure from 0.2 to 1.8 M resulted in a progressive decrease in the specific activity of topoisomerase II in matrices of CEM/VM-1 but not CEM cells, which suggested that the association of the enzyme with the matrix is altered in the resistant cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat.

The contribution of cystathionine gamma-lyase, cystathionine beta-synthase and cysteine aminotransferase coupled to 3-mercaptopyruvate sulphurtransferase to cysteine desulphhydration in rat liver and kidney was assessed with four different assay systems. Cystathionine gamma-lyase and cystathionine beta-synthase were active when homogenates were incubated with 280 mM-L-cysteine and 3 mM-pyridoxal 5'-phosphate at pH 7.8. Cysteine aminotransferase in combination with 3-mercaptopyruvate sulphurtransferase catalysed essentially all of the H2S production from cysteine at pH 9.7 with 160 mM-L-cysteine, 2 mM-pyridoxal 5'-phosphate, 3 mM-2-oxoglutarate and 3 mM-dithiothreitol. At more-physiological concentrations of cysteine (2 mM) cystathionine gamma-lyase and cystathionine beta-synthase both appeared to be active in cysteine desulphhydration, whereas the aminotransferase pathway did not. The effect of inhibition of cystathionine gamma-lyase by a suicide inactivator, propargylglycine, in the intact rat was also investigated; there was no significant effect of propargylglycine administration on the urinary excretion of total 35S, 35SO4(2-) or [35S]taurine formed from labelled dietary cysteine.     

Use of the tyrosine aminotransferase induction system for the demonstration of the signal effect of glucocorticoid hormones

The induction of tyrosine aminotransferase (TAT) in the HTC hepatoma cell line is observed after a single administration of an active steroid. A few minutes of contact between the cells and dexamethasone or corticosterone is sufficient to induce TAT synthesis to its maximal level. When radiolabeled hormones are used, no radioactivity is found in the cell one hour after removal of the hormone from the culture medium, whereas TAT activity remains optimal. Thus, the hormone behaves like a start signal for the optimal synthesis of the enzyme and its continuous presence in the medium is not necessary during the whole induction cycle.     

Endocrine response of postpartum anestrous beef cows to GnRH or PMSG

Forty-one postpartum anestrous Hereford cows, maintained under range conditions, were used to determine the influence of gonadotropin releasing hormone (GnRH) or pregnant mare serum gonadotropin (PMSG) on ovarian function. Anestrous cows were identified by estrous detection with sterile bulls and concentrations of progesterone in plasma obtained weekly. At 45 +/- 2 days postpartum, cows were allotted to the following treatments: (1) control (saline), (2) 100 mug GnRH, (3) 200 mug GnRH, (4) 200 mug GnRH in carboxymethyl cellulose (CMC), (5) 500 IU PMSG, (6) 1,000 IU PMSG or (7) 2,000 IU PMSG. Cows were bled frequently the first day after treatment and then every other day until 85 days postpartum. The LH responses after 100 and 200 mug of GnRH were not significantly different and mixing 200 mug GnRH with CMC before injection did not significantly alter the LH response. During the first 20 days after treatment, neither GnRH nor 500 IU PMSG altered estradiol concentrations in plasma, but treatment of cows with 1,000 or 2,000 IU PMSG resulted in increased (P<0.01) concentrations of estradiol. The time postpartum required for concentrations of progesterone in plasma to exceed 1 ng/ml was reduced (P<0.05) by all treatments except 100 mug GnRH. These data indicate that GnRH causes LH release in anestrous range cows and that treatment with 1,000 or 2,000 IU PMSG initiates ovarian activity as evidenced by increased concentrations of estradiol in plasma.     

Functional similarities of AeEα Ia molecules as determined by analysis with T-cell clones

Recognition of A_eE Ia antigens at the functional level was investigated using T-cell clones. The reactivities of an alloreactive and an antigen-reactive clone, both of which recognized A_eE Ia molecules, were compared on a panel of stimulator/antigen-presenting cells of various genotypes. The two clones recognized all tested A _e ^b E ^x Ia molecules, where x is a haplotype capable of expressing an Ia.7-bearing E polypeptide. Ia antigen recognition by either clone could be inhibited by the monoclonal antibody Y-17, which recognizes a combinatorial serologic determinant on certain A_eE molecules. There were no differences in the recognition of Ia by the alloreactive versus the antigen-reactive clone, suggesting that Ia antigens are recognized by the two clones in a fundamentally similar way. The recognition of these various Ia molecules by the two cloned T-cell lines provides evidence that the E polypeptides from H-2 haplotypes k, d, r, and u are functionally indistinguishable.Abreviations MHC major histocompatibility complex - Mb myoglobin - MLR mixed leukocyte reaction - PBS phosphate buffered saline - APC antigen presenting cell - KLH keyhole limpet hemocyanin - GAT poly (glut⁶⁰ alai³⁰ tyr¹⁰)n - (TG)-A—L poly (L-tyr, L-glu)-poly (D, L-ala)—poly L-lys - GLPhe poly (glu⁵⁵ lys³⁶ phe⁹)n