Ethoxyresorufin‐<i>O</i>‐deethylase induction potency of polychlorinated diphenyl ethers in H4IIE rat hepatoma cells

Koistinen, Jaana; Sanderson, J. Thomas; Giesy, John P.; Nevalainen, Tapio; Paasiv́irta, Jaakko

doi:10.1002/etc.5620151121

Cited by 24 publications

(13 citation statements)

References 41 publications

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“…Therefore, enzyme induction may be due to impurities with Ah-receptor binding affinity present in technical PBDE mixtures. It was shown that PCDF impurities at concentrations < 1% could completely account for the observed EROD activity of all except one of 29 tested polychlorinated diphenyl ether (PCDE) congeners (92). This study demonstrated that in studies with halogenated DEs, it is important to control the presence of potent dibenzofuran and dibenzodioxin impurities, which even at low concentrations can account for considerable biologic activity attributed to the relatively high dosages required for DEs.…”

Section: Experimental Animalsmentioning

confidence: 82%

Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.

Darnerud

Eriksen

Johannesson

et al. 2001

Environ Health Perspect

686

263

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Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in plastics (concentration, 5--30%) and in textile coatings. Commercial products consist predominantly of penta-, octa-, and decabromodiphenyl ether mixtures, and global PBDE production is about 40,000 tons per year. PBDEs are bioaccumulated and biomagnified in the environment, and comparatively high levels are often found in aquatic biotopes from different parts of the world. During the mid-1970--1980s there was a substantial increase in the PBDE levels with time in both sediments and aquatic biota, whereas the latest Swedish data (pike and guillemot egg) may indicate that levels are at steady state or are decreasing. However, exponentially increasing PBDE levels have been observed in mother's milk during 1972--1997. Based on levels in food from 1999, the dietary intake of PBDE in Sweden has been estimated to be 0.05 microg per day. Characteristic end points of animal toxicity are hepatotoxicity, embryotoxicity, and thyroid effects as well as maternal toxicity during gestation. Recently, behavioral effects have been observed in mice on administration of PBDEs during a critical period after birth. Based on the critical effects reported in available studies, we consider the lowest-observed-adverse-effect level (LOAEL) value of the PBDE group to be 1 mg/kg/day (primarily based on effects of pentaBDEs). In conclusion, with the scientific knowledge of today and based on Nordic intake data, the possible consumer health risk from PBDEs appears limited, as a factor of over 10(6) separates the estimated present mean dietary intake from the suggested LOAEL value. However, the presence of many and important data gaps, including those in carcinogenicity, reproduction, and developmental toxicity, as well as additional routes of exposure, make this conclusion only preliminary. Moreover, the time trend of PBDEs in human breast milk is alarming for the future.

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Section: Experimental Animalsmentioning

confidence: 82%

Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.

Darnerud

Eriksen

Johannesson

et al. 2001

Environ Health Perspect

686

263

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“…It cannot be ruled out that the variability observed in toxicity studies with PCDEs is due to contamination of test compounds with potent AhR agonists such as PCDDs and PCDFs [22]. For instance, we were unable to use any PCDE compounds purchased from Ultra Scientific other than PCDE congener 77 for our toxicity tests because of PCDF contamination in μg/g quantities.…”

Section: Resultsmentioning

confidence: 99%

“…In a recent study, various chloro‐, nitro‐, and/or trifluoromethyl‐substituted diphenyl ethers did not induce hepatic ethoxyresorufin O ‐deethylase (EROD) activity in rainbow trout [21]. Koistinen et al [22] reported that several PCDE congeners induced EROD activity in in vitro assays with rat hepatoma (H4IIE) cells, but this activity disappeared when PCDEs were cleaned‐up by Florisil column chromatography; presumably because of chromatographic separation of PCDEs from trace amounts of potent monoxygenase‐inducing contaminants. Many of the biological responses of vertebrates to HAHs, including the induction of hepatic monoxygenases, are mediated by binding to the cytosolic aryl hydrocarbon receptor (AhR), and the strength of binding of these compounds to the AhR appears to be correlated with toxic potency [14,23,24].…”

Section: Introductionmentioning

confidence: 99%

Early life‐stage mortalities of Japanese medaka (Oryzias latipes) exposed to polychlorinated diphenyl ethers

Metcalfe

Cormier

et al. 1997

Enviro Toxic and Chemistry

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Abstract-Polychlorinated diphenyl ethers (PCDEs) are a group of compounds that resemble polychlorinated dibenzofurans in structure that have been detected at ppb concentrations in fish from the Great Lakes. The objective of this project was to determine the toxicological significance of PCDE residues in fish. PCDE congener 77 (3,3Ј,4,4Ј-tetrachlorodiphenyl ether), congener 71 (2,3Ј,4Ј,6-tetrachlorodiphenyl ether), congener 118 (2,3Ј,4,4Ј,5-pentachlorodiphenyl ether), and congener 105 (2,3,3Ј,4,4Ј-pentachlorodiphenyl) were tested for toxicity with early life stages (ELS) of Japanese medaka, Oryzias latipes. These embryotoxicity data showed that the mono-ortho congeners 105 and 118 and the non-ortho congener 77 were embryotoxic to medaka. However, the toxic equivalency factors (TEFs) estimated for congeners 105, 77, and 118 relative to 2,3,7, 8-TCDD were relatively low at 0.00056, 0.00003, and 0.00001, respectively. PCDE compounds were isolated in a fraction prepared from a bulk extract of Lake Ontario lake trout.

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“…Another possibility is that the TCDD‐like porphyrin accumulation response observed in some reports may be due to small quantities of TCDD‐like impurities in the HCB preparations, which generally elicit their responses at micromolar concentrations [43,44]. The importance of verifying purity was recently exemplified by the observation that the ability of polychlorinated diphenyl ether preparations to induce EROD activity in H4IIE rat hepatoma cells was due to low concentrations of PCDF impurities, which were well below 1% [45]. Aryl hydrocarbon‐active impurities, such as PCDDs, PCDFs, and non‐ ortho ‐PCBs were not detected by GC‐MS and GC‐ECD in the HCB preparation used in the present study.…”

Section: Discussionmentioning

confidence: 99%

In vitro induction of ethoxyresorufin‐O‐deethylase and porphyrins by halogenated aromatic hydrocarbons in avian primary hepatocytes

Sanderson

Kennedy

Giesy

1998

Enviro Toxic and Chemistry

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Ethoxyresorufin‐O‐deethylase (EROD) and porphyrin induction responses of primary hepatocytes to halogenated aromatic hydrocarbons (HAHs) were examined in newly hatched domestic chickens, herring gulls, ring‐billed gulls, double‐crested cormorants, and Forster's terns. Concentration–response relationships were determined for both biochemical responses in hepatocyte preparations derived from individual avian livers (except for the tern). The choice of vehicle used to dose chicken hepatocytes greatly affected the potencies and efficacies of HAHs. Dimethyl sulfoxide resulted in median effective concentration (EC50) values for EROD induction that were between 10 and 15 times less than isooctane (isooctane was used throughout the study). Neither vehicle induced EROD activity by itself. Concentration‐dependent increases in EROD activity were observed with several HAHs, and their potencies (EC50 values) were compared to that of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) within each hepatocyte preparation to determine relative potency factors (RPFs). Differences in sensitivity to these responses were observed among individuals within each of the species and among species. Median EC50 values (nM) for EROD induction by TCDD were 0.72, 13, 20, 25, and 150 for the chicken, cormorant, ring‐billed gull, herring gull, and tern hatchling, respectively. Relative potency factors for several HAHs were different, in both ranking and potency, from those generally derived in mammalian hepatocytes. Porphyrin accumulation was observed occasionally with the most potent aryl hydrocarbon receptor agonists, but most HAHs were not tested at concentrations sufficiently high to observe a consistent response. This study provides information on interindividual and interspecies differences in responsiveness to TCDD‐like compounds and provides species‐specific RPFs that may prove useful for the purpose of hazard and risk assessment for fish‐eating birds.

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Ethoxyresorufin‐O‐deethylase induction potency of polychlorinated diphenyl ethers in H4IIE rat hepatoma cells

Cited by 24 publications

References 41 publications

Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.

Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.

Early life‐stage mortalities of Japanese medaka (Oryzias latipes) exposed to polychlorinated diphenyl ethers

In vitro induction of ethoxyresorufin‐O‐deethylase and porphyrins by halogenated aromatic hydrocarbons in avian primary hepatocytes

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