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E Dybing

Publications and source records attributed to E Dybing.

At least 19 recordsLinked to original sources
PubMed2006

Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

Animals↗
PubMed2006

Risk assessment of substances that are both genotoxic and carcinogenic report of an International Conference organized by EFSA and WHO with support of ILSI Europe.

The European Food Safety Authority (EFSA) and the World Health Organization (WHO), with the support of the International Life Sciences Institute, European Branch (ILSI Europe), organized an international conference on 16-18 November 2005 to discuss how regulatory and advisory bodies evaluate the potential risks of the presence in food of substances that are both genotoxic and carcinogenic. The objectives of the conference were to discuss the possible approaches for risk assessment of such substances, how the approaches may be interpreted and whether they meet the needs of risk managers. ALARA (as low as reasonably achievable) provides advice based solely on hazard identification and does not take into account either potency or human exposure. The use of quantitative low-dose extrapolation of dose-response data from an animal bioassay raises numerous scientific uncertainties related to the selection of mathematical models and extrapolation down to levels of human exposure. There was consensus that the margin of exposure (MOE) was the preferred approach because it is based on the available animal dose-response data, without extrapolation, and on human exposures. The MOE can be used for prioritisation of risk management actions but the conference recognised that it is difficult to interpret it in terms of health risk.

Animals↗
PubMed2006

Particulate matter properties and health effects: consistency of epidemiological and toxicological studies.

Identifying the ambient particulate matter (PM) fractions or constituents, critically involved in eliciting adverse health effects, is crucial to the implementation of more cost-efficient abatement strategies to improve air quality. This review focuses on the importance of different particle properties for PM-induced effects, and whether there is consistency in the results from epidemiological and experimental studies. An evident problem for such comparisons is that epidemiological and experimental data on the effects of specific components of ambient PM are limited. Despite this, some conclusions can be drawn. With respect to the importance of the PM size-fractions, experimental and epidemiological studies are somewhat conflicting, but there seems to be a certain consistency in that the coarse fraction (PM10-2.5) has an effect that should not be neglected. Better exposure characterization may improve the consistency between the results from experimental and epidemiological studies, in particular for ultrafine particles. Experimental data indicate that surface area is an important metric, but composition may play an even greater role in eliciting effects. The consistency between epidemiological and experimental findings for specific PM-components appears most convincing for metals, which seem to be important for the development of both pulmonary and cardiovascular disease. Metals may also be involved in PM-induced allergic sensitization, but the epidemiological evidence for this is scarce. Soluble organic compounds appear to be implicated in PM-induced allergy and cancer, but the data from epidemiological studies are insufficient for any conclusions. The present review suggests that there may be a need for improvements in research designs. In particular, there is a need for better exposure assessments in epidemiological investigations, whereas experimental data would benefit from an improved comparability of studies. Combined experimental and epidemiological investigations may also help answer some of the unresolved issues.

Cardiovascular Diseases↗
PubMed2005

Human exposure and internal dose assessments of acrylamide in food.

This review provides a framework contributing to the risk assessment of acrylamide in food. It is based on the outcome of the ILSI Europe FOSIE process, a risk assessment framework for chemicals in foods and adds to the overall framework by focusing especially on exposure assessment and internal dose assessment of acrylamide in food. Since the finding that acrylamide is formed in food during heat processing and preparation of food, much effort has been (and still is being) put into understanding its mechanism of formation, on developing analytical methods and determination of levels in food, and on evaluation of its toxicity and potential toxicity and potential human health consequences. Although several exposure estimations have been proposed, a systematic review of key information relevant to exposure assessment is currently lacking. The European and North American branches of the International Life Sciences Institute, ILSI, discussed critical aspects of exposure assessment, parameters influencing the outcome of exposure assessment and summarised data relevant to the acrylamide exposure assessment to aid the risk characterisation process. This paper reviews the data on acrylamide levels in food including its formation and analytical methods, the determination of human consumption patterns, dietary intake of the general population, estimation of maximum intake levels and identification of groups of potentially high intakes. Possible options and consequences of mitigation efforts to reduce exposure are discussed. Furthermore the association of intake levels with biomarkers of exposure and internal dose, considering aspects of bioavailability, is reviewed, and a physiologically-based toxicokinetic (PBTK) model is described that provides a good description of the kinetics of acrylamide in the rat. Each of the sections concludes with a summary of remaining gaps and uncertainties.

Acrylamide↗
PubMed2004

Release of inflammatory cytokines, cell toxicity and apoptosis in epithelial lung cells after exposure to ambient air particles of different size fractions.

Several studies have shown that particles of smaller size may be more potent than larger to induce inflammatory and toxic responses in cultured lung cells. However, the relative importance of different size fractions of ambient PM to induce such effects is still not known. In this study, we investigated the potency of different size fractions of urban ambient air particles to induce release of inflammatory cytokines in the human alveolar cell line A549 and primary rat type 2 cells. A mineral-rich ambient air PM10 sample collected in a road tunnel (road PM10) was also included. The coarse fraction of the urban ambient air particles demonstrated a similar or higher potency to induce release of the proinflammatory cytokines IL-8/MIP-2 and IL-6 compared to the fine and ultrafine fractions. The coarse fraction was also the most toxic in both cell systems. In contrast to the A549 cells, no induction of cytokine release was induced by the ultrafine particles in the primary type 2 cells. The mineral-rich road PM10 may be equally or more potent than the various size fractions of the ambient air particles to induce cytokines in both cell types. In conclusion, the coarse fraction of ambient particles may be at least as potent by mass as smaller fractions to induce inflammatory and toxic effects in lung cells.

Air Pollutants↗
PubMed2003

Risk assessment of acrylamide in foods.

Daily mean intakes of acrylamide present in foods and coffee in a limited Norwegian exposure assessment study have been estimated to be 0.49 and 0.46 microg per kg body weight in males and females, respectively. Testicular mesotheliomas and mammary gland adenomas have consistently been found in 2-year drinking water rat cancer studies with acrylamide. Acrylamide also shows initiating activity in mouse skin after systemic administration. Since acrylamide is converted to the mutagenic metabolite glycidamide and forms adducts to hemoglobin in rodents and humans, the tumorigenic endpoints in rats were assumed to be an expression of acrylamide genotoxicity. Using the default linear extrapolation methods LED10 and T25, the lifetime cancer hazard after lifelong exposure to 1 microg acrylamide per kg body weight per day, scaled to humans, was calculated to be, on average, 1.3 x 10-3. Using this hazard level and correlating it with the exposure estimates, a lifetime cancer risk related to daily intake of acrylamide in foods for 70 years in males was calculated to be 0.6 x 10-3, implying that 6 out of 10,000 individuals may develop cancer due to acrylamide. For females, the risk values were slightly lower. It must be emphasized that this risk assessment is conservative. A number of processes may result in nonlinearity of the dose-response relationships for acrylamide carcinogenicity in the low-dose region, including detoxication reactions, cell cycle arrest, DNA repair, apoptosis, and immune surveillance. Thus, the true risk levels related to acrylamide intake may be considerably lower.

Acrylamide↗
PubMed2003

Application of toxicological risk assessment principles to the chemical constituents of cigarette smoke.

OBJECTIVE: To provide a hazard prioritisation for reported chemical constituents of cigarette smoke using toxicological risk assessment principles and assumptions. The purpose is to inform prevention efforts using harm reduction. DATA SOURCES: International Agency for Research on Cancer Monographs; California and US Environmental Protection Agency cancer potency factors (CPFs) and reference exposure levels; scientific journals and government reports from the USA, Canada, and New Zealand. STUDY SELECTION: This was an inclusive review of studies reporting yields of cigarette smoke constituents using standard ISO methods. DATA EXTRACTION: Where possible, the midpoint of reported ranges of yields was used. DATA SYNTHESIS: Data on 158 compounds in cigarette smoke were found. Of these, 45 were known or suspected human carcinogens. Cancer potency factors were available for 40 of these compounds and reference exposure levels (RELs) for non-cancer effects were found for 17. A cancer risk index (CRI) was calculated by multiplying yield levels with CPFs. A non-cancer risk index (NCRI) was calculated by dividing yield levels with RELs. Gas phase constituents dominate both CRI and NCRI for cigarette smoke. The contribution of 1,3-butadiene (BDE) to CRI was more than twice that of the next highest contributing carcinogen (acrylonitrile) using potencies from the State of California EPA. Using those potencies from the USEPA, BDE ranked third behind arsenic and acetaldehyde. A comparison of CRI estimates with estimates of smoking related cancer deaths in the USA showed that the CRI underestimates the observed cancer rates by about fivefold using ISO yields in the exposure estimate. CONCLUSIONS: The application of toxicological risk assessment methods to cigarette smoke provides a plausible and objective framework for the prioritisation of carcinogens and other toxicant hazards in cigarette smoke. However, this framework does not enable the prediction of actual cancer risk for a number of reasons that are discussed. Further, the lack of toxicology data on cardiovascular end points for specific chemicals makes the use of this framework less useful for cardiovascular toxicity. The bases for these priorities need to be constantly re-evaluated as new toxicology information emerges.

Dioxins↗
PubMed2002

Development and implementation of the IPCS conceptual framework for evaluating mode of action of chemical carcinogens.

The framework developed by the International Programme on Chemical Safety (IPCS) for assessing the mode of action of tumour induction of chemicals in experimental animals has been illustrated with d-limonene, sodium saccharin, di(2-ethylhexyl)phthalate (DEHP) and sulfamethazine as examples. d-Limonene causes renal tumours only in male rats through a response associated with alpha(2u)-globulin. Sodium saccharin induces urinary bladder tumours only in male rats through formation of a urinary precipitate causing erosion of the bladder surface and extensive regenerative hyperplasia. DEHP causes liver tumours in rats and mice through activation of the receptor PPAR alpha leading to peroxisome proliferation and hepatocellular proliferation. Sulfamethazine induces thyroid follicular cell tumours in rats and mice through a mechanism involving altered thyroid hormone homeostasis.

Carcinogens↗
PubMed2002

Comparability of world-wide analytical data of PCDDs, PCDFs and non-ortho PCBs in samples of chicken, butter and salmon.

It was the primary objective of the present study to elucidate, from a chemical analytical point of view, the comparability of dioxin determinations and the consequences concerning the data on levels in food reported world-wide. To do so, an international intercalibration study on the determination of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like PCBs in three natural food items was performed between March and June 2000. Samples of chicken, butter and salmon, collected in Norway, where sent to 42 laboratories and analysed for 20 PCDDs/PCDFs/non-ortho PCBs. The study generated congener-specific data for the three food matrixes both on wet weight and lipid basis. The reported data from 37 laboratories, in 15 countries, were statistically analysed in order to determine the congener-specific comparability as well as the comparability based on a toxic equivalency value (TEQ). Based on the reported data the mean relative standard deviations (mean RSD) for the WHO98-TEQDFP measurements were found to range from 36% to 57% the three foods. For chicken, the consensus level was 1.2 ppt TEQ on lipid basis, and the reported levels by 24 laboratories were between 0.53 and 2.2 ppt. For butter, the consensus was 0.55 ppt TEQ. 27 laboratories reported levels from 0.18 up to 1.5 ppt. For the salmon, sample levels of 5.9 to 38 ppt TEQ (by 25 laboratories) was reported where 15 ppt was the consensus value. It can thus be concluded that the world-wide data on dioxins, at background levels in foods, are not direct numerically comparable due to inherent analytical reasons. Up to 50% deviations are expected when interlaboratory dioxin results for foods are compared.

Adult↗
PubMed2001

Careers in toxicology in Europe--options and requirements. Report of a workshop organized on behalf of the Individual Members of EUROTOX during the EUROTOX Congress 2000 in London (September 17-20, 2000).

In view of the lack of information regarding careers for toxicologists in Europe, the Individual Members of EUROTOX organised a workshop on careers in toxicology during the EUROTOX Congress 2000 in London. Toxicologists are mainly employed in academia, regulatory agencies, contract research organisations (CROs) and the chemical and pharmaceutical industries. There are also a few governmental institutes involved with toxicological work other than teaching or regulation. Toxicologists can also work as independent consultants, especially for commercial organisations. The requirements for starting a career in any of the above organisations, the need and the advantages and disadvantages of specialisation, and further career prospects are summarised and briefly discussed. The organisations, and also working as an independent toxicology consultant, offer interesting professional work of relevance to modern-day society. There is currently a shortage of toxicologists not only in the traditional field of risk assessment but also especially in new areas, e.g. toxicogenomics. This shortage may be at least in part due to insufficient training opportunities. Further consideration of career opportunities is planned and will be published in due course.

Career Mobility↗
PubMed2001

Foetal growth and duration of gestation relative to water chlorination.

OBJECTIVE: To assess the effect of exposure to chlorination byproducts during pregnancy on foetal growth and duration of pregnancy. METHODS: A population based study was conducted of 137,145 Norwegian children born alive in 1993--5. Information was obtained from the Norwegian medical birth registry, waterwork registry, and social science data service. The outcomes of interest were birth weight, low birth weight (<2500 g), small for gestational age, and preterm delivery (gestational age <37 weeks). The exposure assessment was based on quality of drinking water in the municipality where the mother lived during pregnancy. Municipal exposure was calculated with information on chlorination and the amount of natural organic matter in raw water measured as colour in mg precipitate/l. The main exposure category was high colour and chlorination, which was contrasted with the reference category of low colour and no chlorination. RESULTS: In logistic regression analysis adjusting for confounding, the risks of low birth weight (odds ratio (OR) 0.97, 95% confidence interval (95% CI) 0.89 to 1.06) and small for gestational age (OR 1.00, 95% CI 0.91 to 1.10) were not related to exposure. Contrary to the hypothesis, the risk of preterm delivery was slightly lower among the exposed than the reference category (OR 0.91, 95% CI 0.84 to 0.99). The risks of the studied outcomes were similar in newborn infants exposed to high colour drinking water without chlorination and chlorinated drinking water with low colour compared with the reference category. CONCLUSIONS: The present study did not provide evidence that prenatal exposure to chlorination byproducts at the relatively low concentrations encountered in Norwegian drinking water increases the risk of the studied outcomes.

Birth Weight↗
PubMed2001

A simple method for quantitative risk assessment of non-threshold carcinogens based on the dose descriptor T25.

This report provides guidance for using the dose-descriptor T25 from animal studies as a basis for quantitative risk characterisation of non-threshold carcinogens. T25 is presently used within the European Union for setting specific concentration limits for carcinogens in relation to labelling of preparations (formulations). The T25 is defined as the chronic dose rate which will give 25% of the animals tumours at a specific tissue site, after correction for spontaneous incidence, within the standard life-time of that species. The T25 is converted to the corresponding human dose descriptor, HT25, by dividing it with the appropriate scaling factor for interspecies dose scaling based on comparative metabolic rates. Subsequently, the human dose (expressed in mg per kg body-weight per day) is calculated from the available exposure data. The corresponding human life-time cancer risk is then obtained by using linear extrapolation by dividing the exposure dose with the coefficient (HT25/0.25). The results with this new method, which can easily be calculated without computer programmes, are in excellent agreement with results from computer-based extrapolation methods such as the linearised multistage model and the benchmark method using LED10, even though the present method only takes into consideration one single dose-response point. To overcome possible shortcomings of the present method, the estimated life-time risks are proposed to be accompanied by a commentary statement giving an overall evaluation of data that may have bearing on the carcinogenic risk and that may indicate whether the real human risk is likely to be higher or lower than the calculated life-time risk. By using the present guidance and a harmonized set of criteria and default values, the calculation of life-time cancer risk should be transparent and easy to comprehend.

Animals↗
PubMed2000

Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation.

Many wildlife species may be exposed to biologically active concentrations of endocrine-disrupting chemicals. There is strong evidence obtained from laboratory studies showing the potential of several environmental chemicals to cause endocrine disruption at environmentally realistic exposure levels. In wildlife populations, associations have been reported between reproductive and developmental effects and endocrine-disrupting chemicals. In the aquatic environment, effects have been observed in mammals, birds, reptiles, fish, and mollusks from Europe, North America, and other areas. The observed abnormalities vary from subtle changes to permanent alterations, including disturbed sex differentiation with feminized or masculinized sex organs, changed sexual behavior, and altered immune function. For most reported effects in wildlife, however, the evidence for a causal link with endocrine disruption is weak or nonexisting. Crucial in establishing causal evidence for chemical-induced wildlife effects appeared semifield or laboratory studies using the wildlife species of concern. Impaired reproduction and development causally linked to endocrine-disrupting chemicals are well documented in a number of species and have resulted in local or regional population changes. These include: Masculinization (imposex) in female marine snails by tributyltin, a biocide used in antifouling paints, is probably the clearest case of endocrine disruption caused by an environmental chemical. The dogwhelk is particularly sensitive, and imposex has resulted in decline or extinction of local populations worldwide, including coastal areas all over Europe and the open North Sea. DDE-induced egg-shell thinning in birds has caused severe population declines in a number of raptor species in Europe and North America. Endocrine-disrupting chemicals have adversely affected a variety of fish species. In the vicinity of certain sources (e.g., effluents of water treatment plants) and in the most contaminated areas is this exposure causally linked with the effects on reproductive organs that could have implications for fish populations. However, there is also a more widespread occurrence of endocrine disruption in fish in the U.K., where estrogenic effects have been demonstrated in freshwater systems, in estuaries, and in coastal areas. In mammals, the best evidence comes from the-field studies on Baltic gray and ringed seals, and from the Dutch semifield studies on harbor seals, where both reproduction and immune functions have been impaired by PCBs in the food chain. Reproduction effects resulted in population declines, whereas impaired immune function has likely contributed to the mass mortalities due to morbillivirus infections. Distorted sex organ development and function in alligators has been related to a major pesticide spill into a lake in Florida, U.S.A. The observed estrogenic/antiandrogenic effects in this reptile have been causally linked in experimental studies with alligator eggs to the DDT complex. Although most observed effects currently reported concern heavily polluted areas, endocrine disruption is a potential global problem. This is exemplified by the widespread occurrence of imposex in marine snails and the recent findings of high levels of persistent potential endocrine-disrupting chemicals in several marine mammalian species inhabiting oceanic waters.

Animals↗
PubMed1999

[The outer environment--now and then].

Hazardous environmental factors in Norway have changed considerably over the last decades, often for the better. During the last five-year period, water-works serving 800,000 Norwegians have been renovated. The earlier high levels of sulphur dioxide and lead in urban air are now very low, whereas suspended particulate matter and nitrogen oxides continue to be at levels which can induce adverse health effects. Radon and tobacco smoke are now important indoor contaminants. Moisture-induced damage in dwellings may lead to health problems; the extent of such damage is, however, not known. A number of fjords are still contaminated with metals, PAH (polycyclic aromatic hydrocarbons), PCB (polychlorinated biphenyls) and dioxins, even though industrial discharge to water and air has been greatly reduced. Body burdens of DDT, PCB and dioxins have been markedly lowered over time. There is a continuous increase in the use of chemicals, though the chemicals are better tested and controlled than before. The total volume of pesticides used has fallen over the last three decades. There are no clear changes over the last 15 to 20 years in perceived noise exposure.

Air Pollution↗
PubMed1999

[Possible carcinogenic risk associated with production and use of creosote-treated wood].

Creosote is a coal tar product which contains varying amounts of mutagenic and carcinogenic substances such as polycyclic aromatic hydrocarbons (PAHs) and benzene. Marketing and use of creosote and preparations containing creosote, as well as creosote-treated wood, are regulated by a EU Directive. According to the EU classification of such mixtures, inclusion of a warning against creosote as a carcinogen is not necessary if the contents of benzo[a]pyrene (BaP) and benzene are lower than 50 ppm (parts per million) and 1000 ppm, respectively. A recent well designed skin painting study in mice clearly indicates that the creosote preparations had a five-fold higher potency to induce skin cancer than the potency based on BaP content. Furthermore, it was estimated that creosote containing 50 ppm BaP would induce a significant incidence of skin cancer. Preliminary results from determination of concentrations of various carcinogens (BaP and benzene) in the air close to creosote impregnation plants as well as the crudely estimated exposure of children to dermal contact with creosote-treated wood, indicate that the life-time cancer risk from such exposures is in the order of one per 10,000. Despite the uncertainty related to such estimates, these risk levels give reasons for some concern. A further reduction in the content of PAH and benzene in creosote preparations should be considered.

Animals↗
PubMed1999

Situations with enhanced chemical risks due to toxicokinetic and toxicodynamic factors.

Recognizing toxicokinetic and toxicodynamic variability is important in risk assessment of chemicals and may help to explain interindividual differences in susceptibility in exposed populations. Both toxicokinetic and toxicodynamic factors may be influenced by age and disease processes and show genetic polymorphic variation. Decreased metabolic activity in the very young or very old may enhance chemical toxicity caused by the parent chemical. Similarly, disease processes affecting hepatic metabolism and renal excretion may delay inactivation of many xenobiotics. Genetic polymorphisms may enhance toxicity in rapid metabolizers when the toxicity is caused by a reactive intermediate and increase toxicity in slow metabolizers when the toxicity is caused by a parent chemical. Some cells of the developing conceptus are exquisitely sensitive to chemical exposure. Also, organs and tissues of newborns and elderly individuals may show increased responses toward xenobiotics. In addition, disease-induced altered receptor sensitivity and tissue repair may result in enhanced chemical toxicity. Further, tissue antioxidant defense against radical damage may be compromised under nutritional deficiencies and starvation. Hereditary peculiarities in individual responses to environmental chemicals may be due to polymorphic variation of receptor proteins and tissue repair enzymes, although the database for such variation is quite limited.

Aging↗