Ethylene oxide: evaluation of genotoxicity data and an exploratory assessment of genetic risk

A risk estimate of the heritable effects of ethylene oxide exposure, using the parallelogram approach, as suggested by Frits Sobels, is described. The approach is based on available data on the ethylene oxide-induced responses for the same genetic endpoint in somatic cells of both laboratory animals and humans, and for germ cell mutations in the same laboratory animal. Human germ cell effects are estimated. The available data sets for this approach were evaluated. We consider this as complementary to the genetic risk assessment carried out by U.S. EPA scientists, in which the risk from heritable (reciprocal) translocations induced by ethylene oxide was estimated. In the present study we restricted our assessment to dominant mutations. The sensitivity factor relating mouse to man was based on ethylene oxide-induced HPRT mutant frequencies in lymphocytes in vivo. From this comparison, it could be concluded that occupational exposure for 1 year to 1 ppm ethylene oxide would lead to a risk of a dominantly inherited disease in the offspring of 4 × 10⁻⁴ above the background level. The uncertainty interval of this figure is quite large (0.6–28) × 10⁻⁴. The values are compatible with the existing estimates of the corresponding risk from exposure to low LET radiation when the genotoxic potency ratio of ethylene oxide and radiation is considered. This risk estimation approach has allowed us to identify additional data that are required for a more complete risk estimation of the heritable effects of ethylene oxide, or indeed any mutagenic chemical.     

Information requirements and regulatory approaches for heritable genetic risk assessment and risk communication

With the evolution of genetic toxicology as a scientific discipline and the formation of the Environmental Mutagen Society (EMS), much thought was given to the study of chemicals in the human environment for their mutagenic effects. The Society's goal was to promote scientific investigation and dissemination of information related to genetic toxicology. Subsequently, the concern for chemically induced genetic damage in human germ cells and its potential impact on genetic diseases was detailed in the Committee 17 Report (1975). With new information on the involvement of genetic alterations in disease and on the ramifications of possible effects of exposures to environmental mutagens, it is becoming increasingly necessary to again focus our attention on the assessment of heritable genetic effects. Clearly, strategies for communication of genetic hazard/risk assessments to exposed individuals and to those charged with regulating environmental agents need to be developed.     

Genotoxicity risk assessment: a proposed classification strategy

Recent advances in genetic toxicity (mutagenicity) testing methods and in approaches to performing risk assessment are prompting a renewed effort to harmonize genotoxicity risk assessment across the world. The US Environmental Protection Agency (EPA) first published Guidelines for Mutagenicity Risk Assessment in 1986 that focused mainly on transmissible germ cell genetic risk. Somatic cell genetic risk has also been a risk consideration, usually in support of carcinogenicity assessments. EPA and other international regulatory bodies have published mutagenicity testing requirements for agents (pesticides, pharmaceuticals, etc.) to generate data for use in genotoxicity risk assessments. The scheme that follows provides a proposed harmonization approach in which genotoxicity assessments are fully developed within the risk assessment paradigm used by EPA, and sets out a process that integrates newer thinking in testing battery design with the risk assessment process. A classification strategy for agents based on inherent genotoxicity, dose-responses observed in the data, and an exposure analysis is proposed. The classification leads to an initial level of concern for genotoxic risk to humans. A total risk characterization is performed using all relevant toxicity data and a comprehensive exposure evaluation in association with the genotoxicity data. The result of this characterization is ultimately used to generate a final level of concern for genotoxic risk to humans. The final level of concern and characterized genotoxicity risk assessment are communicated to decision makers for possible regulatory action(s) and to the public.     

基因工程生物的生态影响及其评价

随着基因工程技术的迅速发展,基因工程产生的生物将被广泛地应用于非受控的自然环境中,这将带来诸多的环境和生态方面的问题。本文概述了基因工程生物在非受控环境下可能产生的生态影响,提出了“基因工程生态学”这一新的应用生态学分支领域,探讨了该分支学科的概念、主要研究内容和目标,以及当前应采取的研究策略,并就发展基因工程生态学的有关问题提出了建议。     

生态风险评价及研究进展

生态风险是当前环境管理研究领域中的一个热点问题,其研究着重关注化学、物理和生物的胁迫因子可能对生态系统或其组分的有害影响.生态风险评价对科学制定环境管理决策有着重要的意义.要对生态系统进行有效地管理,必须预测不利生态影响发生的可能性及后果,减小其对于生态系统或某些组分的损害程度.本文对生态风险评价的研究方法、工具以及研究趋势进行了综述,指出了目前生态风险评价中还需要进一步加强的研究领域,认为在当前城市化水平不断提高的情况下要关注城市生态风险,并针对存在的一些问题提出了今后的研究展望.     

A genetic risk tool for obesity predisposition assessment and personalized nutrition implementation based on macronutrient intake

There is little evidence about genetic risk score (GRS)–diet interactions in order to provide personalized nutrition based on the genotype. The aim of the study was to assess the value of a GRS on obesity prediction and to further evaluate the interactions between the GRS and dietary intake on obesity. A total of 711 seekers of a Nutrigenetic Service were examined for anthropometric and body composition measurements and also for dietary habits and physical activity. Oral epithelial cells were collected for the identification of 16 SNPs (related with obesity or lipid metabolism) using DNA zip-coded beads. Genotypes were coded as 0, 1 or 2 according to the number of risk alleles, and the GRS was calculated by adding risk alleles with such a criterion. After being adjusted for gender, age, physical activity and energy intake, the GRS demonstrated that individuals carrying >7 risk alleles had in average 0.93 kg/m² of BMI, 1.69 % of body fat mass, 1.94 cm of waist circumference and 0.01 waist-to-height ratio more than the individuals with ≤7 risk alleles. Significant interactions for GRS and the consumption of energy, total protein, animal protein, vegetable protein, total fat, saturated fatty acids, polyunsaturated fatty acids, total carbohydrates, complex carbohydrates and fiber intake on adiposity traits were found after adjusted for confounders variables. The GRS confirmed that the high genetic risk group showed greater values of adiposity than the low risk group and demonstrated that macronutrient intake modifies the GRS association with adiposity traits.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0445-z) contains supplementary material, which is available to authorized users.     

城市生态风险评价研究进展

随着城市化发展和城市人居环境的恶化,城市生态风险越来越受到关注,但尚缺乏有关城市生态风险评价的深入系统研究.本文依据城市生态学原理及生态风险评价框架从驱动力、风险源、风险受体与评价终点,以及生态风险综合评价方法等方面对城市生态风险评价研究进行综述.指出城市经济社会活动类型与程度是城市生态风险产生的主要驱动力;城市生态系统不同等级功能实体和城市整体是城市生态风险评价中的风险受体;城市生态风险评价终点包括城市生态系统结构、过程、功能要素,以及城市整体水平的性质和功能变化;耦合了社会经济需求的生态系统模型是城市生态风险评价方法的发展方向.未来城市生态风险评价研究应明确生态风险管理具体目标,确定综合性评价终点,建立多指标评价体系和综合评价方法.     

Acrylamide: its metabolism, developmental and reproductive effects, genotoxicity, and carcinogenicity

Monomeric acrylamide is an important industrial chemical primarily used in the production of polymers and copolymers. It is also used for producing grouts and soil stabilizers. Acrylamide's neurotoxic properties have been well documented. This review will focus on pertinent information concerning other, non-neurotoxic, effects observed after exposure to acrylamide, including: its genotoxic, carcinogenic, reproductive, and developmental effects. It will also cover its absorption, metabolism, and distribution. The data show that acrylamide is capable of inducing genotoxic, carcinogenic, developmental, and reproductive effects in tested organisms. Thus, acrylamide may pose more than a neurotoxic health hazard to exposed humans. Acrylamide is a small organic molecule with very high water solubility. These properties probably facilitate its rapid absorption and distribution throughout the body. After absorption, acrylamide is rapidly metabolized, primarily by glutathione conjugation, and the majority of applied material is excreted within 24 h. Preferential bioconcentration of acrylamide and/or its metabolites is not observed although it appears to persist in tests and skin. Acrylamide can bind to DNA, presumably via a Michael addition-type reaction, which has implications for its genotoxic and carcinogenic potential. The available evidence suggests that acrylamide does not produce detectable gene mutations, but that the major concern for its genotoxicity is its clastogenic activity. This clastogenic activity has been observed in germinal tissues which suggest the possible heritability of acrylamide-induced DNA alterations. Since there is 'sufficient evidence' of carcinogenicity in experimental animals as outlined under the U.S. EPA proposed guidelines for carcinogen risk assessment, acrylamide should be categorized as a 'B2' carcinogen and therefore be considered a 'probable human carcinogen.' The very limited human epidemiological data do not provide sufficient evidence to enable one to judge the actual carcinogenic risk to humans. Acrylamide is able to cross the placenta, reach significant concentrations in the conceptus and produce direct developmental and post-natal effects in rodent offspring. It appears that acrylamide may produce neurotoxic effects in neonates from exposures not overtly toxic to the mothers. Acrylamide has an adverse effect on reproduction as evidenced by dominant lethal effects, degeneration of testicular epithelial tissue, and sperm-head abnormalities.     

Ionizing radiation and genetic risks VII. The concept of mutation component and its use in risk estimation for Mendelian diseases

The responsiveness of Mendelian diseases to an increase in the mutation rate is studied by using the concept of the mutation component (MC) of genetic diseases. Algebraic expressions to evaluate MC at any specific generation following either a one-time or a permanent increase in mutation rate are derived and are illustrated with numerical examples. For a one-time increase in mutation rate, the analysis shows that the first generation MC for autosomal dominant diseases is equal to the selection coefficient; this is also true for X-linked diseases (adjusted for the proportion of X-chromosomes in males). For autosomal recessive diseases the first generation MC is substantially smaller than that for autosomal dominants. In subsequent generations MC gradually decays to zero. Under conditions of a permanent increase in the mutation rate, the MC for autosomal dominant, X-linked and completely recessive autosomal disorders progressively increases to reach a value of one at the new equilibrium. For incompletely recessive autosomal disorders, however, the MC at equilibrium can be larger than one. The rates of approach to the new equilibrium are different for the different classes of diseases, dictated by selection and time (in generations) following radiation exposure. The effects of increases in mutation rate on MC are more pronounced for autosomal dominants, followed by X-linked and are far less for autosomal recessives. Even for autosomal dominants, the early generation effects of radiation exposures would not be appreciable unless the heterozygotes have a severely reduced fitness.     

区域生态风险管理研究进展

近20a来,随着生态风险评价研究的不断深化,区域生态风险评价的理论和方法日臻完善,与此紧密相关的生态风险管理日益受到了广泛关注.生态风险管理具有基于监控的反馈机制、风险受害者参与、程序灵活非线性化、关注成本效益等共同点.总结了国内外生态风险管理的研究进展,发现近年来生态风险管理的研究多是基于生态风险评价的结果,针对不同的风险类型和等级采取不同的管理措施.国内现有的研究对灾害风险管理的体系、机制建设较为成熟,但区域生态风险管理的机制研究尤其是预警和防范方面研究尚不成熟.基于此,构建了基于风险来临前、风险到来时和风险过后的区域生态风险管理的基本框架,研究结果对生态风险管理理论的构建和实践应用具有重要的意义.     

Finding fault with health risk assessment: A typology for risk assessment criticism

Although systematic, quantitative assessment of environmental health risks is a staple of regulatory decision-making, complaints regarding its perceived failures and shortcomings are an intrinsic feature of the policy landscape. In this article, we (a) catalog the classic criticisms of conventional health risk assessment, (b) create a typology that orders the critiques according to their focus on either input errors or output biases, and (c) identify selected allegations that fall within each category. We also note that the risk assessment–risk management paradigm has evolved over the past several decades, partially in accordance with the general direction and spirit of these classic critiques. The debate continues today along familiar lines invoking the traditional critiques and rebuttals outlined here.     

Children's health risk assessment: incorporating a lifestage approach into the risk assessment process

This overview paper provides the historical context for the incorporation of lifestage‐specific concerns in human health risk assessment, briefly explains the process employed in a lifestage framework for risk assessment, and discusses the scientific rationale for how utilizing lifestage data will strengthen the overall risk assessment process. This risk assessment approach will add value by: (1) providing a more complete evaluation of the potential for vulnerability at different lifestages, including a focus on the underlying biological events and incorporation of mode of action information related to different critical developmental periods; (2) evaluating the potential for toxicity during all lifestages after early lifestage exposure; (3) reviewing the importance of integrating exposure information and adverse health effects across lifestages; and (4) serving as a basis to extend some aspects of the children's health risk assessment framework to all lifestages. Birth Defects Res (Part B), 2008. © 2008 Wiley‐Liss, Inc.     

外来植物的入侵机制及其生态风险评价

外来植物入侵已成为严重威胁生态系统健康发展的全球性问题,预防优于治理,对外来植物进行生态风险评价可有效地防御和降低入侵风险。本文基于生态风险评价理论,通过对外来植物入侵特性和过程的分析,探讨了外来植物入侵生态风险的评价方法。将评价程序分为风险源分析、风险受体评价、暴露与危害评价、风险综合评价和风险管理对策5部分,初步建立了风险源评价指标体系,以及度量生态损失和生态风险的指标和公式,进而得出外来植物入侵综合生态风险评价的方法。     

Harmonia axyridis: an environmental risk assessment for Northwest Europe

In this paper, we summarize the international situation with respect to environmental risk assessment for biological control agents. Next, we apply a recently designed, comprehensive risk evaluation method consisting of a stepwise procedure to evaluate the environmental risks of Harmonia axyridis in Northwest Europe. This resulted in the very clear conclusion that H. axyridis is a potentially risky species for Northwest Europe, because it is able to establish, it has a very wide host range including species from other insect orders and even beyond the class of Insecta, it may feed on plant materials, it can cover large distances (>50 km per year), it does move into non-target areas, it may attack many non-target species including beneficial insects and insects of conservation concern, its activities have resulted in the reduction of populations of native predators in North America, it is known as a nuisance in North America and recently also in Northwest Europe, and it may develop as a pest of fruit in North America. Considering the H. axyridis case, current knowledge would lead to the conclusion that, although the predator is capable to effectively control several pest species, its risks are manifold and it should, thus, not have been released in Northwest Europe. At the time of the first releases in Nortwest Europe in 1995, the available scientific literature made clear that H. axyridis is a large sized polyphagous predator and has a great reproductive capacity in comparison with other ladybird beetles, and that there was a need to study non-target effects because of its polyphagous behaviour. In retrospect, this information should have been sufficient to reject import and release of this species, but it was apparently ignored by those who considered release of this predator in Northwest Europe. The case of Harmonia releases in Northwest Europe underlines that there is an urgent need for harmonized, world-wide regulation of biological control agents, including an information system on risky natural enemy species.     

The capture of heritable variation for genetic quality through social competition

In theory, females of many species choose mates based on traits that are indicators of male genetic quality. A fundamental question in evolutionary biology is why genetic variation for such indicator traits persists despite strong persistent selection imposed by female preference, which is known as the lek paradox. One potential solution to the lek paradox suggests that the traits that are targets of mate choice should evolve condition-dependent expression and that condition should have a large genetic variance. Condition is expected to exhibit high genetic variance because it is affected by a large number of physiological processes and hence, condition-dependent traits should 'capture' variation contributed by a large number of loci. We suggest that a potentially important cause of variation in condition is competition for limited resources. Here, we discuss a pair of models to analyze the evolutionary genetics of traits affected by success in social competition for resources. We show that competition can contribute to genetic variation of 'competition-dependent' traits that have fundamentally different evolutionary properties than other sources of variation. Competition dependence can make traits honest indicators of genetic quality by revealing the relative competitive ability of males, can provide a component of heritable variation that does not contribute to trait evolution, and can help maintain heritable variation under directional selection. Here we provide a general introduction to the concept of competition dependence and briefly introduce two models to demonstrate the potential evolutionary consequences of competition-dependent trait expression.     

Regulatory aspects of genotoxicity testing: from hazard identification to risk assessment

This symposium focused on the use of tests for chromosomal damage, and other genotoxicity measures, for detection of potentially harmful chemicals. The speakers discussed the information that has been gained over the last three decades about the use of "short-term tests" for genotoxicity in cultured cells and in animals (mainly rodents), and the ongoing debates about the rational use of data from such experimental systems in trying to extrapolate to an understanding of potential human risk. The overall theme was that the field of regulatory toxicology currently is over-reliant on qualitative outcomes of in vitro hazard-screening tests, generally conducted at the maximum achievable exposures, and needs a more realistic approach that incorporates in vivo exposure levels and dose-response information.     

Ecological risk assessment of transgenic plant releases: an Austrian perspective

Some prerequisites for ecological risk assessment of transgenic plant releases are examined, with the aim of identifying research needs in Austria. Austria harbours high habitat diversity, extending from the Alps to the Pannonian continental lowlands. The Pannonian flora includes potential cross-breeding partners of several crops, which do not occur in western Europe. The border zones of major biogeographical regions contain high biodiversity, both in terms of species and habitat diversity; whether the genetic variability of widespread plant species is also increased in these areas requires further investigation. Especially in Alpine regions, transgenic grasses might eventually cause profound changes in community structure. Ecological risk assessment of transgenic crop releases should not only consider adverse effects on non-target species and ecosystems, but also their likely impact on the agroecosystems.     

Fear in animals: a meta-analysis and review of risk assessment

The amount of risk animals perceive in a given circumstance (i.e. their degree of 'fear') is a difficult motivational state to study. While many studies have used flight initiation distance as a proxy for fearfulness and examined the factors influencing the decision to flee, there is no general understanding of the relative importance of these factors. By identifying factors with large effect sizes, we can determine whether anti-predator strategies reduce fear, and we gain a unique perspective on the coevolution of predator and anti-predator behaviour. Based on an extensive review and formal meta-analysis, we found that predator traits that were associated with greater risk (speed, size, directness of approach), increased prey distance to refuge and experience with predators consistently amplified the perception of risk (in terms of flight initiation distance). While fish tolerated closer approach when in larger schools, other taxa had greater flight initiation distances when in larger groups. The presence of armoured and cryptic morphologies decreased perception of risk, but body temperature in lizards had no robust effect on flight initiation distance. We find that selection generally acts on prey to be sensitive to predator behaviour, as well as on prey to modify their behaviour and morphology.