Biomedical subjects

Jörg Oehlmann

Publications and source records attributed to Jörg Oehlmann.

14 recordsLinked to original sources

PubMed2007

Prosobranch snails as test organisms for the assessment of endocrine active chemicals--an overview and a guideline proposal for a reproduction test with the freshwater mudsnail Potamopyrgus antipodarum.

Recently, prosobranch snails have been recommended as promising candidates for test organisms for the assessment of endocrine active chemicals. Three prosobranch snail species, the freshwater mudsnail Potamopyrgus antipodarum, the freshwater ramshorn snail Marisa cornuarietis, and the marine netted whelk Nassarius reticulatus are portrayed and their respective biotests are presented together with results of laboratory experiments and biological effect monitoring surveys in the field. All characterized species are highly sensitive toward xeno-androgens [triphenyltin (TPT), tributyltin (TBT), methyltestosterone (MT) and fenarimol (FEN)], and xeno-estrogens [bisphenol A (BPA), octylphenol (OP), ethinylestradiol], and show effects at environmentally relevant, rather low concentrations in laboratory experiments. For exposure to the xeno-androgen TPT, EC(10) values range between 15.9 and 29.0 ng as Sn/L (sediment 0.03 mug as Sn/kg), for TBT, EC(10) values are found between 3.42 and 37.8 ng as Sn/L (sediment 2.98 microg as Sn/kg) and effect concentrations for FEN are calculated as 18.6 ng/L (EC(10)) and 0.19 microg/kg (EC(50) sediment; EC(10) not calculable). Exposure to xeno-estrogens yielded EC(10 )values of 13.9 ng/L (0.19 microg/kg) for BPA, a NOEC of <1 microg/L (EC(10) of 0.004 microg/kg) for OP and a NOEC of 1 ng/l (EC(10) sediment of 2.2 microg/kg) for ethinylestradiol. Responses to androgens comprised the development of imposex and the reduction of fertility or embryo production, effects of estrogens included the stimulation of egg production and embryo production, and the increased weight of glands. Also, biological effect monitoring studies with P. antipodarum and N. reticulatus in several rivers or estuarine areas revealed the capacity of the biotests to detect an androgenic or estrogenic potential of sediment samples. A comparison of the three test species with regard to sensitivity and practical aspects in routine application favors the freshwater mudsnail P. antipodarum for a standardized procedure, and this reproduction test will be introduced into the OECD guideline program for standardization in the near future.

Animals↗

PubMed2007

Endocrine disruption in prosobranch molluscs: evidence and ecological relevance.

Prosobranch snails represent almost 50% of all recent molluscs, are ubiquitously distributed, play important roles in various ecosystems and exhibit a variety of reproductive modes and life-cycle-strategies. Many of them attain life spans of several years, which in combination with their limited ability to metabolize organic chemicals, may contribute to the fact that prosobranchs constitute one of the most endangered taxonomic groups in aquatic ecosystems. Although it is not yet known to what extent endocrine disrupting chemicals (EDCs) contribute to this situation, the case of tributyltin (TBT) and its population-level impact on prosobranchs demonstrates the general susceptibility of these invertebrates. The existing evidence for comparable population-level effects in prosobranch snails by other androgens, antiandrogens, and estrogens is critically reviewed. The example of TBT demonstrates the difficulty to prove an endocrine mode of action for a given chemical. Although it is generally accepted that TBT causes imposex and intersex in prosobranch snails as a result of endocrine disruption, the detailed biochemical mechanism is still a matter of debate. The strengths and weaknesses of the five competing hypotheses are discussed, together with previously unpublished data. Finally, the ecological relevance of EDC effects on the population and community level and the application of prosobranchs for the assessment of EDCs are addressed.

Animals↗

PubMed2007

Effects of cadmium and tributyltin on development and reproduction of the non-biting midge Chironomus riparius (Diptera): baseline experiments for future multi-generation studies.

In this study the effects of tributyltin (TBT) and cadmium (Cd) were tested on the freshwater arthropod Chironomus riparius (Diptera) in life-cycle experiments. To this end, the OECD guideline 218 was extended with reproduction relevant parameters (e.g. number of fertile egg masses per female). Based on these reproduction data the number of larvae for next generation and the population growth rate were calculated. Experiments were performed using environmentally relevant concentrations of the test substances in the sediment (nominal ranges: 50-200 micro g Sn/kg and 0.2-2.1 mg Cd/kg, on a dry weight basis). Quartz sand was used as sediment in order to develop a test system for a following research project, focusing on the effects of TBT and Cd as model stressors on C. riparius populations in multi-generation studies. Both model stressors caused significant effects on development and reproduction of C. riparius. Larval mortality proved to be a sensitive parameter and a clear concentration-response relationship was observed with a significant increase (P < 0.001) at the highest TBT concentration and at a Cd concentration of 1.17 mg Cd/kg dw (P < 0.05). The two highest TBT concentrations emergence was significantly (P < 0.05) delayed compared to the solvent control. For Cd a clear prolonged average main emergence interval was observed, but not for TBT. TBT and Cd inhibited also oviposition. These effects resulted in a concentration-depended reduction of the population growth rate.

Animals↗

PubMed2006

Sexual dimorphism in esterified steroid levels in the gastropod Marisa cornuarietis: the effect of xenoandrogenic compounds.

Molluscs can conjugate a variety of steroids to form fatty acid esters. In this work, the freshwater ramshorn snail Marisa cornuarietis was used to investigate sex differences in endogenous levels of esterified steroids. Testosterone and estradiol were mainly found in the esterified form in the digestive gland/gonad complex of M. cornuarietis, and males had higher levels of esterified steroids than females (4-10-fold). Additionally, the ability of several xenobiotics, namely tributyltin (TBT), methyltestosterone (MT) and fenarimol (FEN) to interfere with the esterification of testosterone and estradiol was investigated. All three compounds induced imposex - appearance of male sexual characteristics in females. Exposure to TBT led to a decrease in both esterified testosterone (60-85%) and estradiol (16-53%) in females after 100 days exposure, but had no effect on males. Exposure to FEN and MT did not alter levels of esterified steroids in males or in females, although exposed females developed imposex after 150 days exposure. The decrease in esterified steroids by TBT could not be directly linked with a decrease in microsomal acyl-CoA:testosterone acyltransferase (ATAT) activity, which catalyzes the esterification of steroids. In fact, ATAT activity was marginally induced in organisms exposed to TBT for 50 days (1.3-fold), and significantly induced in males and females exposed to MT for 50 days (1.8- and 1.5-fold, respectively), whereas no effect on ATAT activity was observed after 150 days exposure.

Androgens↗

PubMed2006

Is there a causal association between genotoxicity and the imposex effect?

There is a growing body of evidence that indicates common environmental pollutants are capable of disrupting reproductive and developmental processes by interfering with the actions of endogenous hormones. Many reports of endocrine disruption describe changes in the normal development of organs and tissues that are consistent with genetic damage, and recent studies confirm that many chemicals classified to have hormone-modulating effects also possess carcinogenic and mutagenic potential. To date, however, there have been no conclusive examples linking genetic damage with perturbation of endocrine function and adverse effects in vivo. Here, we provide the first evidence of DNA damage associated with the development of imposex (the masculinization of female gastropods considered to be the result of alterations to endocrine-mediated pathways) in the dog-whelk Nucella lapillus. Animals (n = 257) that displayed various stages of tributyltin (TBT) -induced imposex were collected from sites in southwest England, and their imposex status was determined by physical examination. Linear regression analysis revealed a very strong relationship (correlation coefficient of 0.935, p < 0.0001) between the degree of imposex and the extent of DNA damage (micronucleus formation) in hemocytes. Moreover, histological examination of a larger number of dog-whelks collected from sites throughout Europe confirmed the presence of hyperplastic growths, primarily on the vas deferens and penis in both TBT-exposed male snails and in females that exhibited imposex. A strong association was found between TBT body burden and the prevalence of abnormal growths, thereby providing compelling evidence to support the hypothesis that environmental chemicals that affect reproductive processes do so partly through DNA damage pathways.

Animals↗

PubMed2006

COMPRENDO: Focus and approach.

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that "the dose makes the poison" may not always be the case because some EDCs do not induce the classical dose-response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters--Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates) .

Androgens↗

PubMed2006

Bisphenol A induces superfeminization in the ramshorn snail Marisa cornuarietis(Gastropoda: Prosobranchia) at environmentally relevant concentrations.

Previous investigations have shown that bisphenol A (BPA) induces a superfeminization syndrome in the freshwater snail Marisa cornuarietis at concentrations as low as 1 microg/L. Superfemales are characterized by the formation of additional female organs, enlarged accessory sex glands, gross malformations of the pallial oviduct, and a stimulation of egg and clutch production, resulting in increased female mortality. However, these studies were challenged on the basis of incomplete experimentation. Therefore, the objective of the current approach was to bridge several gaps in knowledge by conducting additional experiments. In an initial series of experiments, study results from the reproductive phase of the snails were evaluated in the sub-micrograms per liter range. Before and after the spawning season, superfemale responses were observed [NOEC (no observed effect concentration) 7.9 ng/L, EC10 (effective concentration at 10%) 13.9 ng/L], which were absent during the spawning season. A further experiment investigated the temperature dependence of BPA responses by exposing snails at two temperatures in parallel. The adverse effect of BPA was at least partially masked at 27 degrees C (EC10 998 ng/L) when compared with 20 degrees C (EC10 14.8 ng/L). In M. cornuarietis, BPA acts as an estrogen receptor (ER) agonist, because effects were completely antagonized by a co-exposure to tamoxifen and Faslodex. Antiandrogenic effects of BPA, such as a significant decrease in penis length at 20 degrees C, were also observed. Competitive receptor displacement experiments indicate the presence of androgen- and estrogen-specific binding sites. The affinity for BPA of the estrogen binding sites in M. cornuarietis is higher than that of the ER in aquatic vertebrates. The results emphasize that prosobranchs are affected by BPA at lower concentrations than are other wildlife groups, and the findings also highlight the importance of exposure conditions.

Animals↗

PubMed2005

Impact of a flood disaster on sediment toxicity in a major river system--the Elbe flood 2002 as a case study.

The ecotoxicological implications of a flooding disaster were investigated with the exceptional Elbe flood in August 2002 as an example. Sediment samples were taken shortly after the flood at 37 sites. For toxicity assessment the midge Chironomus riparius (Insecta) and the mudsnail Potamopyrgus antipodarum (Gastropoda) were exposed to the sediment samples for 28 days. For a subset of 19 sampling sites, the contamination level and the biological response of both species were also recorded before the flood in 2000. The direct comparison of biological responses at identical sites revealed significant differences for samples taken before and immediately after the flood. After flood sediments of the river Elbe caused both higher emergence rates in the midge and higher numbers of embryos in the mudsnail. Contrary to expectations the toxicity of the sediments decreased after the flood, probably because of a dilution of toxic substances along the river Elbe and a reduction in bioavailability of pollutants as a result of increasing TOC values after the flood.

Disasters↗

PubMed2005

Reproductive stimulation by low doses of xenoestrogens contrasts with the view of hormesis as an adaptive response.

We discuss the similarities and differences of two types of effects that occur at low but not high doses of chemicals: hormesis and stimulation by oestrogenic endocrine-disrupting chemicals or xenoestrogens. While hormesis is a general phenomenon evoked by many compounds, oestrogenic stimulation occurs for specific chemicals that disrupt actions of endogenous oestrogen. Both types of phenomena can induce an inverted-U dose-response curve, resulting from low-dose stimulation of response, and thus challenge current methods of risk assessment. Hormesis is generally thought to be caused by an over-reaction of detoxification mechanisms, which is considered an adaptive response that should protect an organism from subsequent stress. One view of the hormetic low-dose stimulatory response, i.e., increased performance, is that it is beneficial. In contrast, we propose that for manmade xenoestrogens this is never the case. This is demonstrated with examples for low doses of the oestrogenic environmental chemicals bisphenol A and octylphenol, and the oestrogenic drug diethylstilbestrol. Adverse low-dose effects include oviduct rupture, an enlarged prostate, feminization of males and reduced sperm quality. These adverse stimulatory effects divert energy needed for other processes, resulting in reduced fitness. In conclusion, while there are similarities (inverted-U dose-response), there are also differences, adaptive response for hormesis versus adverse stimulatory response for low doses of manmade xenoestrogens, that have been almost totally ignored in discussions of hormesis. We propose that the risk posed by low doses of manmade xenoestrogens that show inverted-U dose-response curves is underestimated by the current threshold model used in risk assessment, and this is likely to apply to other endocrine-disrupting chemicals.

Animals↗

PubMed2005

Description and initial evaluation of a Xenopus metamorphosis assay for detection of thyroid system-disrupting activities of environmental compounds.

A need is recognized for the development and evaluation of bioassays for detection of thyroid system-disrupting compounds. The issue of testing for thyroid disruption can be addressed by exploiting amphibian metamorphosis as a biological model. In the present study, a test protocol for a Xenopus metamorphosis assay (XEMA) was developed and its interlaboratory transferability was evaluated in an informal ring test with six laboratories participating. In the XEMA test, exposure of Xenopus laevis tadpoles was initiated at stages 48 to 50 and continued for 28 d. Development and growth of tadpoles were assessed by means of developmental stage and whole body length determinations, respectively. For initial test protocol evaluation, thyroxine (T4), and propylthiouracil (PTU) were used as positive controls for thyroid system-modulating activity, and ethylenethiourea (ETU) was used as a test compound. Exposure of tadpoles to 1 microg/L T4 produced a significant acceleration of metamorphosis whereas PTU concentrations of 75 and 100 mg/L completely inhibited metamorphosis. Five different ETU concentrations (5, 10, 25, 50, and 100 mg/L) were tested and a concentration-dependent inhibition of metamorphosis was observed. None of the compounds affected tadpole survival, and only PTU caused a slight retardation in tadpole growth. This study demonstrates that the XEMA test provides a sensitive, robust, and practical testing approach for detection of compounds with both agonistic and antagonistic effects on the thyroid system in Xenopus tadpoles.

Animals↗

PubMed2004

Bioaccumulation of 14C-17alpha-ethinylestradiol by the aquatic oligochaete Lumbriculus variegatus in spiked artificial sediment.

A bioaccumulation study was performed with the endobenthic freshwater oligochaete Lumbriculus variegatus MULLER exposed to the radiolabelled synthetic steroid 17alpha-ethinylestradiol (14C-EE2) in a spiked artificial sediment. Concentration of total radioactivity increased constantly and almost linearly during 35 days of exposure. The accumulation factor normalised to worm lipid content and sediment TOC (AFlipid/OC) was 75 at the end of the uptake period, but a steady state was not reached. Uptake kinetics were calculated fitting the measured AFs to a kinetic rate equation for constant uptake from sediment using iterative non-linear regression analysis. After 10 days of elimination in contaminant-free sediment 50% of the accumulated total radioactivity was excreted by the worms. Extracts from L. variegatus sampled at the end of the uptake phase were analysed by thin layer chromatography (TLC). The results showed that 6% of the total radioactivity incorporated by the worms was 14C-EE2. After treatment of extracts with beta-glucuronidase the amount of 14C-EE2 increased to 84%. These results suggest that L. variegatus has the potency to accumulate high amounts of conjugated EE2. Hence, a transfer of EE2 to benthivores and subsequent secondary poisoning of predators might be possible.

Animals↗

PubMed2004

Evidence for endocrine disruption in invertebrates.

The issue of endocrine disruption (ED) in invertebrates has generated remarkably little interest in the past compared to research with aquatic vertebrates in this area. However, with more than 95% of all known species in the animal kingdom, invertebrates constitute a very important part of the global biodiversity with key species for the structure and function of aquatic and terrestrial ecosystems. Despite the fact that ED in invertebrates has been investigated on a smaller scale than in vertebrates, invertebrates provide some of the best documented examples for deleterious effects in wildlife populations following an exposure to endocrine-active substances. The article provides an overview of the diversity in endocrine systems of invertebrates. The principal susceptibility of invertebrates to endocrine-active compounds is demonstrated with the case studies of tributyltin effects in mollusks and of insect growth regulators, the latter as purposely synthesized endocrine disrupters. The additional evidence for ED in invertebrates from laboratory and field studies is summarized as an update and amendment of the EDIETA report from 1998. Finally, conclusions about the scale and implications of the observed effects are drawn and research needs are defined.

Animals↗

PubMed2003

Stimulated embryo production as a parameter of estrogenic exposure via sediments in the freshwater mudsnail Potamopyrgus antipodarum.

The effects of three suspected endocrine disrupting chemicals, the xeno-estrogens bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-n-nonylphenol (NP), were investigated in a whole-sediment biotest with the freshwater mudsnail Potamopyrgus antipodarum (Gastropoda, Prosobranchia). Artificial sediments were spiked with five nominal concentrations (six for NP), ranging from 1-300 microg/kg dry weight (1-1000 microg/kg for NP). After 2, 4 and 8 weeks of exposure, the responses of the test species were analysed. P. antipodarum exhibited a distinct increase in the number of embryos sheltered in its brood pouch in a time- and concentration-dependent manner in comparison to the solvent control sediment for BPA and OP. The number of "new", still unshelled embryos turned out to be the most sensitive parameter. The lowest observed effect concentration (LOEC) was equivalent to the lowest administered concentration (1 microg/kg for each test compound) for most parameters after 8 weeks of exposure. The calculation of effect concentrations resulted in even lower values for BPA (unshelled embryos after 2 weeks: EC(10) 0.22 microg BPA/kg, EC(50) 24.5 microg BPA/kg; after 4 weeks: EC(10) 0.19 microg BPA/kg, EC(50) 5.67 microg BPA/kg) and OP (unshelled embryos after 4 weeks: EC(10) 4 ng OP/kg, EC(50) 0.07 microg OP/kg). For NP, there was no clear concentration-dependent response, and therefore, no EC(10) or EC(50) could be estimated, but the data suggest an inverted u-shape type of curve. The LOEC in the experiments with NP was 10 microg/kg. Our results indicate that P. antipodarum is highly sensitive to the tested endocrine disruptors at environmentally relevant concentrations. Furthermore, the biotest with P. antipodarum is a useful tool for the identification of sediment-bound pollutants and for the assessment of sediment quality.

Analysis of Variance↗

PubMed2003

Toxicity of triphenyltin and tributyltin to the freshwater mudsnail Potamopyrgus antipodarum in a new sediment biotest.

The effects of two suspected endocrine-disrupting chemicals, the xeno-androgens triphenyltin (TPT) and tributyltin (TBT), were investigated in a new whole-sediment biotest with the freshwater mudsnail Potamopyrgus antipodarum (Gastropoda, Prosobranchia). Artificial sediments were spiked with seven concentrations, ranging from 10 to 500 microg nominal TPT-Sn/kg dry weight and TBT-Sn/kg dry weight, respectively. We analyzed the responses of the test species after two, four, and eight weeks exposure. For both compounds, P. antipodarum exhibited a sharp decline in the number of embryos sheltered in its brood pouch in a time- and concentration-dependent manner in comparison to the control sediment. The number of new, still unshelled embryos turned out to be the most sensitive parameter. The lowest-observed-effect concentration (LOEC) was equivalent to the lowest administered concentration (10 microg/kg of each test compound) for most parameters and thus no no-observed-effect concentration (NOEC) could be established. The calculation of effect concentrations (EC10) resulted in even lower values for both substances (EC10 after eight weeks for unshelled embryos: 0.03 microg TPT-Sn/kg, EC10 after four weeks for unshelled embryos: 0.98 microg TBT-Sn/kg). Our results indicate that P. antipodarum is highly sensitive to both endocrine disruptors TPT and TBT at environmentally relevant concentrations.

Animals↗