Environmental Chemical Risk Research Articles

The significance of information frameworks in integrated risk assessment and management

We present an analysis of frameworks for information on integrated risk assessment and management, focusing on issues related to environmental and health risks of chemicals and their regulation at the EU level. By frameworks we understand the conceptual and procedural constructs within which information is assimilated, processed and given meaning. We examine different aspects of integrated risk information and how these are handled in different frameworks. We mainly address integration in relation to policy, specifically in risk evaluation and risk–benefit considerations, in interaction of assessment and management, and in policy level uncertainties. We show how the policy level influences the frameworks and hence the level and use of integrated assessments, and how they interact with new information and scientific frameworks in EU chemicals control such as the REACH legislation. We conclude that by paying better attention to the nature of the framework it is possible to focus on the most crucial aspects of integration. In this way it is possible to develop appropriate flexible assessments that focus on key complexities and issues without getting entrenched in details of minor significance for the policy problem at hand.

A Terrestrial Food-Chain Bioaccumulation Model for POPs

Mechanistic bioaccumulation models for fish and piscivorous food-webs are widely used to assess the environmental hazard and risk of commercial chemicals, develop water quality criteria and remediation objectives, and conduct exposure assessment of pesticides in aquatic systems. Similar models for mammals and terrestrial food-webs are largely absent. As a result, the hazards and risks of bioaccumulative substances in mammals, birds, and humans remain unrecognized by regulators, and current globally used criteria for identifying bioaccumulative substances only apply to water-breathing organisms and are inadequate for protecting air-breathing organisms including mammals, birds, and human beings. In this paper, we develop and test a modeling framework that can be used to estimate the biomagnification potential and the organism-soil bioaccumulation factor of organic commercial chemicals in terrestrial food-chains. We test the model for the soil-earthworm-shrew food-chain and apply the model to illustrate that (i) chemicals with an octanol-air partition coefficient (K(OA)) < 10(5.25) do not biomagnify even if the K(ow) is high and optimal for biomagnification in fish; (ii) chemicals with a K(OA) > or = 105.25 and a K(ow) between 10(1.75) and 10(12) have a biomagnification potential unless they are metabolized at a sufficiently rapid rate (e.g., in excess of 0.3 d(-1) or a half-life time of 2.5 d for shrews).

Quantitative structure carcinogenicity relationship for detecting structural alerts in nitroso-compounds

Prevention of environmentally induced cancers is a major health problem of which solutions depend on the rapid and accurate screening of potential chemical hazards. Lately, theoretical approaches such as the one proposed here – Quantitative Structure–Activity Relationship (QSAR) – are increasingly used for assessing the risks of environmental chemicals, since they can markedly reduce costs, avoid animal testing, and speed up policy decisions. This paper reports a QSAR study based on the Topological Substructural Molecular Design (TOPS-MODE) approach, aiming at predicting the rodent carcinogenicity of a set of nitroso-compounds selected from the Carcinogenic Potency Data Base (CPDB). The set comprises nitrosoureas (14 chemicals), N-nitrosamines (18 chemicals) C-nitroso-compounds (1 chemical), nitrosourethane (1 chemical) and nitrosoguanidine (1 chemical), which have been bioassayed in male rat using gavage as the route of administration. Here we are especially concerned in gathering the role of both parameters on the carcinogenic activity of this family of compounds. First, the regression model was derived, upon removal of one identified nitrosamine outlier, and was able to account for more than 84% of the variance in the experimental activity. Second, the TOPS-MODE approach afforded the bond contributions – expressed as fragment contributions to the carcinogenic activity – that can be interpreted and provide tools for better understanding the mechanisms of carcinogenesis. Finally, and most importantly, we demonstrate the potentialities of this approach towards the recognition of structural alerts for carcinogenicity predictions.

Novel DNA Polymerases and Novel Genotoxicity Assays

Human genome is continuously exposed to exogenous and endogenous genotoxic agents. The most hazardous and ubiquitous exogenous mutagen may be cigarette smoke, which contains more than 4,000 chemicals including about 60 known carcinogens. About 1% of oxygen metabolism leads to production of reactive oxygen species, a major source of endogenous mutagens. These genotoxic agents induce a variety of lesions in DNA, which results in mutations and chromosome aberrations upon replication. If such genetic alterations occurred in the genes involved in cell proliferations and/or maintenance of genome stability, the cells would proceed in multi-steps of carcinogenesis. The goal of environmental mutagenesis and genetic toxicology is to elucidate the mechanistic links between exposure to genotoxic agents and the health consequences, and to prevent the health hazard associated with DNA damage. To this end, we have investigated the mechanisms of mutagenesis induced by environmental chemicals and contributed to establish the paradigm that Y-family DNA polymerases play central roles in mutagenesis via translesion DNA synthesis across damaged bases in DNA. We also developed genotoxicity assays with bacteria and mice to evaluate the potential risk of environmental chemicals. Here, I review the roles of Y-family DNA polymerases in mutagenesis and introduce features of the novel bacterial and rodent genotoxicity assays. Future directions of environmental mutagenesis and carcinogenesis are also discussed.

The costs of REACH

Early next year, the European Union (EU) plans to implement a major piece of legislation—about 1,200 pages in its current form—to replace 40 different laws regulating the use of chemicals across the member states. When the European Commission (EC) presented its first draft in May 2003 (EC, 2003), it immediately drew huge attention because of its far‐reaching consequences, not only economic but also on human health and the environment. If passed, the REACH legislation will require the chemical industry to provide information on the potential negative effects—most of which are still unknown—of a vast number of chemicals used throughout the EU. Not surprisingly, this has met with criticism from all quarters. The costs of obtaining this information, and the subsequent effects on the European chemical industry, are hotly disputed. > [REACH] immediately drew huge attention because of its far‐reaching consequences, not only economic but also on human health and the environment REACH dictates new rules on the Registration, Evaluation and Authorisation of CHemicals. It requires manufacturers and downstream users of chemicals to register their substances—if they are sold in the EU as isolated compounds or in preparations—either with a national regulatory authority or a central European Chemical Agency, which the EC plans to establish next year in Helsinki, Finland. Companies are required to submit a registration dossier for each product, listing possible adverse effects on human health or the environment. REACH also requires additional authorization for substances that the EC considers of “very high concern”: chemicals that are carcinogenic, mutagenic or toxic to the reproductive system; endocrine disruptors; or persistent, bioaccumulative and toxic substances. Producers or downstream users must perform a risk assessment to ascertain whether their product creates risks to human health or the environment, which social benefits it provides, and whether safer alternatives are available. If, on the basis …

Balancing risks

Regulatory policies designed to reduce the health risk of environmental and/or synthetic chemicals generally aim for zero or negligible levels. Foods, on the other hand, especially those with a long history in the human diet, have been treated as essentially safe, even though they too contain various chemicals including nutrients. The recent debate on the presence in food of acrylamide, a possible human carcinogen, is likely to shake up the traditional paradigm held by regulatory agencies on chemical health risks. The current stance on the safety of acrylamide in food seems to be an extension of the traditional approach to assessment of environmental and/or synthetic chemicals. However, even foods which have long been a part of the human diet contain components that do not necessarily meet the safety margins applied to environmental and/or synthetic chemicals. In the future, a greater understanding of the effect of these agents on biological systems as well as the development of analytical methods for testing will result in many questions being raised concerning chemicals in foods, such as acrylamide which is under scrutiny today. Regulatory policies currently employ various standards for controlling chemical risk. These standards are dependent upon the labeling of the chemical in question, e.g., whether carcinogenic or non-carcinogenic, synthetic or natural, or whether a food or industrial chemical. Regardless of labeling, all chemicals to which we are exposed should be evaluated on an equal footing. Then, according to the level of the identified health risk, regulations could or could not be applied based on local circumstances, e.g., public acceptance, voluntary risk vs. involuntary risk, etc. In order to create a standardized system for chemical risk assessment, the introduction of uniform measures is essential. Loss of life expectancy (LLE) is one possible measure to assess chemical health risk. When LLE has been used, animal toxicity data have indicated that an ad libitum diet intake has considerably more impact on health risk than the acrylamide concentration of the ingested food. Reassessing the health effects of chemicals with a system of uniform measures could reveal many risks that need to be preferentially addressed above and beyond keeping minor toxicants to zero or negligible levels. Recognition of such risks may result in changes that conflict with existing regulations. In any case, whether consciously or unconsciously, people have always been exposed to a certain degree of chemical risk in their daily life. Based on the premise that the public can accept some degree of chemical risk in balance with other risks in their lives, regulatory bodies should be able to take a flexible and effective approach. In order to efficiently and comprehensively maximize the protection of our health against potential harm from chemicals using limited public resources, it is now time for regulatory agencies to restructure their policy frameworks across categories for controlling chemical health risks.

The Environment and Male Fertility: Recent Research on Emerging Chemicals and Semen Quality

Scientific and public concern about the potential risk of environmental chemicals to male reproductive health has been heightened by reports of downward trends in semen quality, as well as increased rates of developmental urogenital tract anomalies and testicular cancer. Of particular concern is whether some contemporary-use environmental chemicals alter semen quality. Specific toxicants of interest include phthalates and pesticides, as well as polychlorinated biphenyls (PCBs). The human data on the relationship of semen quality with phthalate and pesticide exposure are limited and do not currently allow for a definitive conclusion on whether adult exposure, at background environmental levels, alters semen quality. However, the epidemiologic data support an inverse association of PCBs with reduced semen quality, specifically reduced sperm motility. The associations found were generally consistent across studies despite a range of PCB levels. In addition to the chemicals discussed, there are additional classes of chemicals that require further study on their relation with human semen quality.

Making Sense of Ecotoxicological Test Results: Towards Application of Process-based Models

The environmental risk of chemicals is routinely assessed by comparing predicted exposure levels to predicted no-effect levels for ecosystems. Although process-based models are commonly used in exposure assessment, the assessment of effects usually comprises purely descriptive models and rules-of-thumb. The problems with this approach start with the analysis of laboratory ecotoxicity tests, because only a limited amount of information is extracted. Standard summary statistics (NOEC, ECx, LC50) are of limited use in part because they change with exposure duration in a manner that varies with the tested species and the toxicant. As an alternative, process-based models are available. These models allow for toxicity measures that are independent of exposure time, make efficient use of the available data from routine toxicity tests, and are better suited for educated extrapolations (e.g., from individual to population, and from continuous to pulse exposure). These capabilities can be used to improve regulatory decisions and allow for a more efficient assessment of effects, which ultimately will reduce the need for animal testing. Process-based modeling also can help to achieve the goals laid out in REACH, the new strategy of the European Commission in dealing with chemicals. This discussion is illustrated with effects data for Daphnia magna, analyzed by the DEBtox model.

Factores de riesgo para el neuroblastoma

NB is the most frequent pediatric cancer arising in the sympathetic nervous system and represents a serious healthcare challenge because: 1) it is the most frequent neoplasm in the first decades of life; 2) it biological behavior is unpredictable (spontaneous regression, maturation to ganglioneuroma, and localized and metastasized variants); and 3) little is known about most of the risk factors involved in its etiopathogenesis. The objective of this study was to disseminate knowledge of constitutional and environmental (physical, chemical, biological and social) risk factors linked to the development of neuroblastoma (NB), with various levels of scientific evidence. To seek collaboration among pediatricians in the research project "Environment and Pediatric Cancer". We performed a systematic review of the literature published in the previous 25 years on risk factors for NB diagnosed in the first two decades of life, using Medline, the Science Citation Index and Embase. Search profiles were: "neuroblastoma/childhood sympathetic nervous system neoplasms and risk factors/etiology/epidemiology". The most interesting articles and the most relevant references contained therein were selected. With greater or lesser scientific evidence, the following risk factors increase the risk of developing NB: genetic factors; geographic factors; ethnic factors; socioeconomic factors; infectious factors; physical factors; parental occupational exposure; gestational factors; and perinatal and maternal factors. Preventive factors associated with a lower risk of developing NB are breastfeeding and intake of vitamin supplements during pregnancy. The main barriers to the identification of evidence-based risk factors involved in the development of NB are its complex biology and clinical course, its relative rarity and the difficulty of performing epidemiological studies. Research on constitutional and environmental factors involved in its etiopathogenesis should be stimulated. The best preventive strategy is to recommend breastfeeding for more than 6 months.

Risk Assessment of Short-Chain Chlorinated Paraffins in Japan Based on the First Market Basket Study and Species Sensitivity Distributions

The chemical risks of short-chain chlorinated paraffins (SCCPs) to human health and ecological species in Japan were assessed in this study. SCCPs are used as extreme pressure additives in metal-working fluids and flame retardant agents in plastic materials. The first market basket study with a high resolution gas chromatography and mass spectrometry with electron capture negative ionization is reported. Total daily food intakes for Japanese residents of different ages were estimated using Latin Hypercube simulations, and the highest 95th percentile intake is 6.8 x 10(2) ng/kg/day for a 1-year-old child. Based on the reported no-observed-adverse-effect-level (NOAEL) and the estimated exposure mainly from food, it was concluded thatSCCPs are not posing risks to humans in Japan. Ecological risks to aquatic and sediment organisms were estimated using species sensitivity distributions. The 95th percentiles of the distributions obtained by fitting several environmental SCCP concentration data of river water and sediment were 41.8 ng/L and 558 ng/g wet weight as the possible highest concentrations, respectively. No-observed-effect-concentrations (NOEC) were determined by calculating the fifth percentiles of a species sensitivity distribution, which were 2.2 microg/L for aquatic organisms and 1.7 to 13.5 mg/ kg wet weight for sediment organisms. While it is likely that there is no imminent environmental chemical risk for aquatic organisms at a regional level in Japan, this study concluded that a more detailed risk assessment is necessary for sediment organisms.

The Current State of Knowledge About the Effects, Risks, and Science of Children’s Environmental Exposures

In the preface1 to this supplement, we pointed out that pediatricians and other clinicians have made major contributions to the discovery of environmental toxicants. Many acute illnesses that are caused by high exposures to some toxicants are clinically diagnosable or at least are commonly in the differential diagnosis, eg, organophosphate poisoning, infant botulism, acute lead encephalopathy, carbon monoxide poisoning, acrodynia, hypervitaminosis A and some cases of aplastic anemia, convulsions, asthma, respiratory distress, methemoglobinemia, Reyes syndrome, kernicterus, and many of the recognizable syndromes that result from exposures to teratogenic drugs and chemicals. In contrast to the obvious effects of high exposures to environmental toxicants, there is less information and less certainty concerning the magnitude of the contribution of many low exposures of environmental toxicants to morbidity, mortality, and subtle alterations in children as well as adults or how the effects of these exposures vary with age or chronicity of exposure. We also informed the readership that we were going to address the issue of environmental toxicology from both a clinical and a toxicologic viewpoint. Very low exposures to environmental toxicants may lead to diseases that resemble many common illnesses that have other causes, or they may lead to decrements in functioning that are subtle or nonspecific. It is an almost insurmountable task for individual practitioners to conclude a cause-and-effect relationship from low exposures to environmental toxicants among patients in the physician’s patient population. Only well-planned, sophisticated epidemiologic and animal studies can answer the questions that pertain to the toxicity of low-level exposures to environmental toxicants, given that not all individuals will be affected equally, if at all, at any particular level of exposure. Many of the previous multi-authored compendia that have been published by groups of scientists have been unified in their conclusions that environmental toxicants are a very serious … Reprint requests to (R.L.B.) Rm 308, R/A, Alfred I. duPont Hospital for Children, Box 269, Wilmington, DE 19899. E-mail rbrent{at}nemours.org

General principles for risk assessment of living modified organisms: Lessons from chemical risk assessment

Modern biotechnology has led to the development and use of Living Modified Organisms (LMOs) for agriculture and other purposes. Regulators at the national level are increasingly depending on risk assessment as a tool for assessing potential adverse effects of LMOs on the environment and human health. In addition, the Cartagena Protocol on Biosafety, an international agreement expected to enter into force in the near future, requires risk assessment as the basis for decision-making regarding import of some LMOs. While LMO risk assessment is relatively new, there are other risk assessment disciplines which have developed over longer time periods. The field of assessment of the environmental and human health risks of chemicals is particularly well developed, and is similar in application to LMO risk assessment. This paper aims to draw lessons for LMO risk assessment from the vast experience with chemical risk assessment. Seven general principles are outlined which should serve as a useful checklist to guide assessments of risks posed by LMOs.

The development of toxicity tests for freshwater pollutants and their validation in stream and pond mesocosms

The number and variety of freshwater species and bioassay procedures currently recommended in European Directives for assessing the risk posed by pollutants to freshwater ecosystems is rather limited. The aim of the three consecutive European Commission-sponsored programmes described here was to modify or develop new laboratory methods that could be used for evaluating toxicity to freshwater species and which would be suitable for incorporation into the current “notification scheme” for new substances. An essential phase of each project was a validation process in which results of laboratory tests were compared with values obtained in the field using structural and functional responses of communities. The laboratory tests were developed by Fraunhofer-Institut für Umweltchemie und Ökotoxikologie (FhG) Potsdam-Rehbrücke with algae, protozoa and a variety of in vitro cellular/subcellular preparations; by the State University of Ghent with water column invertebrates, and by Cardiff University with benthic invertebrates. The laboratory tests included in vitro procedures, conventional whole organism single species tests, simple multi-species systems and microcosms. The field validation was carried out by Shell Research Sittingbourne employing artificial streams and by FhG Schmallenberg and GSF-Forschungszentrum für Umwelt und Gesundheit, Munich with artificial ponds and included single species responses but also structural and functional community responses. The same reference chemicals: lindane, copper, 3,4-dichloroaniline and atrazine were used by all laboratories. A comparison of the most sensitive toxicity response determined for each reference chemical using the laboratory toxicity tests, with that determined by the field simulation procedures revealed that for the reference chemicals lindane, copper and atrazine, adverse effects were not detected either for single organisms or for structural and functional characteristics of the community or ecosystem, at concentrations below those identified in the laboratory toxicity tests. In the case of dichloroaniline, however, effects on the population dynamics of one species in the pond mesocosm were recorded at a concentration ×16 below that reported in the laboratory. We conclude that appropriately designed, relatively simple and inexpensive laboratory toxicity tests with a selection of test species are generally adequate, with small application factors, for predicting the environmental risk of polluting chemicals to freshwater ecosystems.

Foreword

Abstract Modern chemistry is one of the essential tools in pursuing better medical care, more efficient telecommunications and informatics, and increased agricultural production. However, certain chemicals produced and used in large quantities might cause various hazards in environmental sectors, owing to their global (trans-boundary) translocation, as well as their intrinsically hazardous properties. To reduce environmental risk of such chemicals, international regulatory measures have already been taken [e.g., in response to the initiatives of the Intergovernmental Forum in Chemical Safety (IFCS)], including legally binding implementations and national capacity building in developing countries. Herein lies the urgent need for promoting worldwide research into green chemistry (sustainable chemistry), in which the invention and application of chemical products and processes are designed to reduce or to eliminate the use and generation of hazardous substances. Indeed, green chemistry should encompass a variety of disciplines of fundamental chemistry in IUPAC, to encourage new trends of chemical research. Moreover, results of these researches could be effectively applied for solving environmental problems related to the production and use of chemicals and to create a new chemical industry in the future. As such, green chemistry research conforms completely to the mission-oriented activity of IUPAC to meet regulatory requirements for achieving environmentally sound management of chemicals. We sincerely hope that the present special issue highlighting the state of the art and future prospects of green chemistry research will encourage all chemists who intend to serve society through their research efforts. J. Miyamoto Past-President of IUPAC Chemistry and the Environment Division The increasing knowledge in natural sciences and the application of this knowledge are the driving forces for the development and welfare of mankind. Chemistry plays a central role in this development. Chemistry provides the molecular understanding of physical properties of materials and other matters and thus closely interacts with physics. Chemistry also provides the molecular understanding of living systems and is the basis for modern biology and medicine. The development and opportunities of synthetic chemistry have opened a new dimension for tailor-made materials and compounds for specific purposes. The driving forces for developments in chemistry have been very strong, and there is a demand for new and efficient processes and chemicals. Aspects of sustainable and environmentally friendly processes and chemicals have sometimes been lagging behind this demand. Fortunately, chemistry also provides the tools for a green and sustainable development. Knowledge in this general area has to be integrated into the planning of all research and development in chemistry. There are specific research topics related to the development of green and sustainable processes, which need the input of new technology and novel chemistry. The present Symposium-in-Print provides an overview of recent research and development in the field. We hope that it will stimulate further activities in the field. It is planned as a first step in an IUPAC action on this subject. The IUPAC Organic and Biomolecular Chemistry Division is grateful to its Subcommittee on Organic Synthesis and particularly Professor Pietro Tundo for initiating and engaging in this action, and to him and Profs. David StC. Black and Sofia Memoli for editing the Symposium-in-Print. Torbjörn Norin President of IUPAC Organic and Biomolecular Chemistry Division

Environmental Chemical Exposures and Risk of Herpes Zoster

This study investigated whether residence in Aberdeen, North Carolina, the location of the Aberdeen pesticides dumps site (a national priority list Superfund site containing organochlorine pesticides, volatile organic compounds, and metals), is associated with immune suppression as indicated by a higher incidence of herpes zoster and recent occurrences of other common infectious diseases. Study participants included 1,642 residents, 18-64 years of age, who responded to a telephone survey concerning potential occupational and recreational exposures to pesticides and other chemicals, lifetime history of herpes zoster (shingles), and the recent occurrence of other common infectious diseases. Stratified and logistic regression analyses were used to compare the cumulative incidence of herpes zoster among Aberdeen residents and residents of nearby communities. There was little evidence of an overall increased risk of herpes zoster among Aberdeen residents during the period 1951-1994 [relative risk (RR), 1.3; 95% confidence interval (CI), 0.8-2.1]. However, an elevated risk of herpes zoster was noted consistently among Aberdeen residents of younger ages as compared to residents of the nearby communities. The RR was 2.0 (CI, 1.0-4.0) among those 18-40 years of age and was not affected by controlling for potential confounders. The RR of herpes zoster was also consistently elevated in all age groups for the period before 1985. No differences were noted between residents of Aberdeen and those of the nearby communities with respect to the recent occurrence of other common infectious diseases. These results support the plausibility of an association between exposure to the Aberdeen pesticides dumps site and immune suppression and the potential use of herpes zoster as a marker of immune suppression in studies of environmental chemical exposures.

Environmental chemical exposures and risk of herpes zoster.

This study investigated whether residence in Aberdeen, North Carolina, the location of the Aberdeen pesticides dumps site (a national priority list Superfund site containing organochlorine pesticides, volatile organic compounds, and metals), is associated with immune suppression as indicated by a higher incidence of herpes zoster and recent occurrences of other common infectious diseases. Study participants included 1,642 residents, 18-64 years of age, who responded to a telephone survey concerning potential occupational and recreational exposures to pesticides and other chemicals, lifetime history of herpes zoster (shingles), and the recent occurrence of other common infectious diseases. Stratified and logistic regression analyses were used to compare the cumulative incidence of herpes zoster among Aberdeen residents and residents of nearby communities. There was little evidence of an overall increased risk of herpes zoster among Aberdeen residents during the period 1951-1994 [relative risk (RR), 1.3; 95% confidence interval (CI), 0.8-2.1]. However, an elevated risk of herpes zoster was noted consistently among Aberdeen residents of younger ages as compared to residents of the nearby communities. The RR was 2.0 (CI, 1.0-4.0) among those 18-40 years of age and was not affected by controlling for potential confounders. The RR of herpes zoster was also consistently elevated in all age groups for the period before 1985. No differences were noted between residents of Aberdeen and those of the nearby communities with respect to the recent occurrence of other common infectious diseases. These results support the plausibility of an association between exposure to the Aberdeen pesticides dumps site and immune suppression and the potential use of herpes zoster as a marker of immune suppression in studies of environmental chemical exposures.

Environmental chemical exposures and risk of herpes zoster

Environmental chemical exposures and risk of herpes zoster

Partitioning of chemicals—important factors in exposure assessment of offshore discharges

The CHARM ( chemical hazard assessment and risk management) model was developed to give operators, chemical suppliers, and environmental authorities a scientific framework for analyzing the environmental hazard and risk of offshore chemicals used and discharged to the marine environment. This paper presents results from an R and D project carried out on partitioning of typical offshore chemicals where the objective was to validate the partitioning algorithms in CHARM. The work included further development and verification of the HPLC (OECD 117) method for determining oil/water partitioning, or fraction released of production chemicals, for evaluation of the applicability of the Shake Flask method (OECD 107) and modification of the sediment/water partitioning test methods, as well as establishment of a calculation method for determining the weighted average log P ow for chemical mixtures of homologs. The calculation method was recommended adopted in CHARM. Based on the experimental partitioning results, the CHARM partitioning algorithms were evaluated. The test results showed that the HPLC technique is a “robust” method for determining the P ow, but has limitations for surfactants and chemicals with high log P ow-values, which are typical offshore chemicals. The traditional correlations reported between P ow, the BCF, the fraction of a chemical released with produced water, and the P sw is not valid for typical surfactants. Another approach is therefore used in CHARM, which also was evaluated in this project. There is, however, a need for further validation of the CHARM partitioning algorithms.

Finnish-Estonian Congress of Toxicology Environmental and Health Risks of Industrial Chemicals, Tartu, 22-24 May 1997

Finnish-Estonian Congress of Toxicology Environmental and Health Risks of Industrial Chemicals, Tartu, 22-24 May 1997

Future approaches to genetic toxicology risk assessment

Short-term genetic toxicology tests were developed for the purpose of identifying chemical carcinogens in the environment. After two decades of development and validation, the tests are well-established in routine testing schemes, but our views of their utility for safety evaluation have undergone re-assessment. The correlation between identified mutagens and identified carcinogens has turned out to be significantly less than one. Processes or mechanisms that are not directly genotoxic appear to play a role in carcinogenesis. While short term test data are still components of the assessment of carcinogenic risk, genetic damage also has been recognized as important in its own right, in relation to heritable genetic risk and other health-related effects, such as aging, reproductive failure and developmental toxicity. The revolution in molecular biology and genetic analysis occurring over the past 20 years has contributed to the wealth of new information on the complexities of cell regulation, differentiation, and the carcinogenic process. These technologies have provided new experimental approaches to genetic toxicology assessments, including transgenic cell and animal models, human monitoring, and analysis of macromolecular interactions at environmentally relevant exposures. The potential exists for the development of more efficient and more relevant genetic toxicology testing schemes for use assessing human safety. A delineation of contemporary needs, a modern view of the elements of cancer induction, and an examination of new assays and technologies may provide a framework for integrating new approaches into current schemes for evaluating the potential genetic and carcinogenic risk of environmental chemicals.