Chemical compound safety: typology of competency accreditation for assay centers and analytical laboratories

The use of chemicals warrants many benefits on which modern society is entirely dependent. On the other hand, the lack of reliable information about the impact of the use of chemicals raises increasing concern. In order to guarantee the safety of chemicals it is mandatory to proceed to risk assessment, which in turn consists of hazard evaluation and exposure estimation. These activities are strictly dependent upon the availability of reliable data and information, produced by, e.g., test facilities, test laboratories and clinical laboratories, the specific competence of which has been properly recognised. All this applies in the pre-marketing phase as well as during the use of chemical substances. In this latter phase it is necessary to carry out an appropriate monitoring of environment, food and, in specific situations, human beings (biological monitoring). In the field of chemical safety, standards, legal instruments and operative instruments are nowadays available. These tools make it possible to assess both the quality of data and the competence of the entities involved in the production of the data themselves.     

Towards a toxic-free environment: perspectives for chemical risk assessment approaches.

Regulatory frameworks to control chemical exposure in general living and occupational environments have changed exposure scenarios towards a widely spread contamination at relatively low doses in developed countries. In such evolving context, some critical aspects should be considered to update risk assessment and management strategies. Risk assessment in low-dose chemical exposure scenarios should take advantage of: toxicological investigations on emerging substances of interest, like those recognised as endocrine disruptors or increasingly employed nanoscale materials; human biological monitoring studies aimed to identify innovative biomarkers for known chemical exposure; “omic” technologies useful to identify hazards of chemicals and their modes of action. For updated risk assessment models, suitable toxicological studies, analyses of dose-responses at low-concentrations, environmental and biological monitoring of exposure, together with exposome studies, and the proper definition of susceptible populations may all provide helpful contributions. These may guide defining preventive measures to control the exposure and develop safe and sustainable chemicals by design. Occupational medicine can offer know-how and instruments to understand and manage such evolution towards a toxic-free environment to protect the safety and health of the workforce and, in turn, that of the general population.     

Guidance values for the biomonitoring of occupational exposure. State of the art

Biomonitoring was developed for the assessment of the health risks from exposure to chemicals at work, and the approaches and concepts of biomonitoring are derived from such exposures. At present, biomonitoring is increasingly used also to assess exposure from the environment. Biomonitoring and assessment of external exposure are complementing activities, where the exposure assessments are much more widely applied, especially when the number of chemicals concerned is considered; environmental analysis also offers the distinct advantage of speciation analysis--which is very poorly developed for biomonitoring. Biomonitoring on the other hand provides information on exposure from all sources, and via all absorption routes, and considers also accumulation of the chemical in the body. Bio monitoring using exposure biomarkers thus consider interindividual differences in the absorption, while use of effec biomarkers ideally also considers interindividual differences in sensitivity. Few effect biomarkers, however, have been validated. The major challenges of biomonitoring are the development of monitoring methods, which are inexpensive enough to be applied at a frequency that makes possible meaningful biomonitoring of chemicals with a short half-time; development of exposure biomarker guidance values specific to individual species of different metals; ex pansion of the repertoire of validated effect biomarkers; and validation and application to effect monitoring of the omic technologies. Another major challenge is a reconsideration of the basis of biomonitoring action limits to reflec the change in the work place: Biomonitoring should be adapted to assist in the generation of a healthy workplace which is capable of attracting workers, and assist them to perform their work effectively--rather than just to guarantee absence of serious health effects.     

Human exposure to polychlorinated biphenyls at toxic waste sites: investigations in the United States

Beginning in 1982, environmental and population data were evaluated from waste sites contaminated with polychlorinated biphenyls (PCBs). Pilot exposure assessment studies were conducted at 12 sites where risks of human exposure were thought to be greatest. Serum PCB levels in persons at highest risk of nonoccupationally related exposures (because of their self-reported frequencies and types of activities in contaminated areas) at 10 sites were within background ranges, even though environmental contamination levels as high as 2.5 parts per billion (ppb) in monitoring well water samples and 330,000 ppb in soil samples were measured. At the 2 remaining sites, elevated serum levels were found in these high-risk persons, which require further evaluation by community surveys. These results illustrate that, despite elevated environmental contaminant levels, unless uptake of chemicals above background exposure levels can be demonstrated, adverse health effects cannot be attributed to waste site chemicals. However, health risks due to background exposure levels, as well as in populations with elevated PCB body burdens need further study.     

人体慢性低剂量农药暴露生物学监测研究进展

人体慢性低剂量农药暴露的生物学监测对于评估农药暴露对人体健康的影响有重要意义。生物学监测的标本来源除了目前使用广泛的尿液及血液标本,唾液、汗水、头发等也被用作农药暴露的生物学监测。监测的指标可以直接检测各种生物标本中的农药本身的化学物质及其代谢产物的含量,还可以通过间接指标如酶学、神经递质、DNA、蛋白质进行检测。选择合适的生物学监测方法可以为正确评估人体农药暴露提供有力的依据。本文对目前人体慢性低剂量农药暴露的生物学监测方法进行综述。     

The U.S. National Health and Nutrition Examination Survey and human exposure to environmental chemicals

Researchers are increasingly interested in using human biomonitoring - the measurement of chemicals, their metabolites or specific reaction products in biological specimens/body fluids - for investigating exposure to environmental chemicals. General population human biomonitoring programs are useful for investigating human exposure to environmental chemicals and an important tool for integrating environment and health. One of these programs, the National Health and Nutrition Examination Survey (NHANES), conducted in the United States is designed to collect data on the health and nutritional status of the noninstitutionalized, civilian U.S. population. NHANES includes a physical examination, collecting a detailed medical history, and collecting biological specimens (i.e., blood and urine). These biological specimens can be used to assess exposure to environmental chemicals. NHANES human biomonitoring data can be used to establish reference ranges for selected chemicals, provide exposure data for risk assessment, and monitor exposure trends.     

Grundsatzpapier zur Ableitung von HBM-Werten

Human biomonitoring (HBM) is a useful measure for detecting chemical exposures of the general population. HBM assessment values are required for the assessment of potential health risks associated with the presence of chemicals in blood, urine or other biological matrices. Since 1996, the German HBM Commission has derived statistical reference values and several toxicologically founded assessment values (HBM I and HBM II).The assessment values are based on human exposure–response data, and since 2007, according to the extended concept, also on external dose-derived guidance values such as tolerable daily intakes (TDI). The HBM I value represents the concentration of a substance in human biological material below which—according to the knowledge and judgement of the Commission and with regard to the substance under consideration—no risk for adverse health effects and, consequently, no need for action is expected. The HBM II value represents the concentration of a substance in a human biological material above which an increased risk for adverse health effects exists and, consequently, an acute need for exposure-reduction measures and for the provision of medical advice results. The HBM II value should thus be regarded as an intervention or action level. Further development of HBM values by the German HBM Commission follows the concept of a toxicological point of departure (POD) and use of assessment factors (AFs) based on ECHA recommendations, conceptually similar to biomonitoring equivalents (BE). The development of the three different procedures is described. The latter approach broadens the range of chemicals for which assessment values can be derived.     

Future need for development of occupational exposure databases in Hungary

The data on the occupational exposure measured by the hygienic network laboratories in Hungary were collected during the last 20 years. The data refer to the air pollutant chemicals and to the biological monitoring. The structure of the database of occupational exposure that has been used in the last decade is intended to be changed according to the guideline of the European Working Group on Exposure Registers in Europe. The current databases on the occupational exposure contain data only related to the substances responsible for air pollution. It would be desirable to complement the database with data from the biological monitoring, which also characterize the occupational exposure. It would then be possible to harmonize two distinct databases, and the risk assessment of the employees would become more thorough. This practice would require close cooperation of several organizations. It is desirable to set minimum requirements against the measurement techniques, thus, giving results that are accepted in the exposure database. It is necessary to encourage the use of direct reading instruments in collecting the exposure data and to complement the requirements of the strategies of data collection and the system of evaluation.     

Expert judgement of poisonings and human biomonitoring--the BfR three-level and matrix model

German physicians are obligated (Para 16e Chemicals Law) to submit essential data on poisonings to the Centre for Documentation and Assessment of Poisonings at the Federal Institute for Risk Assessment (Bundesinstituts für Risikobewertung, BfR). In addition, German poison centres are subjected to compulsory reporting of their findings of general importance gained in the context of their activities. The BfR assessment of poisonings has important significance for human case data collection, risk identification, and German toxicological monitoring. Using more than 60,000 reports on cases of poisoning, the BfR developed a structured expert judgement trial for poisonings. This judgement is based on a three-level model, accompanied by two different matrix procedures for an enhanced and more exact assessment of the exposures and the causality between health impairment and exposure. Particularly for low-dose exposures, human biomonitoring data is extremely valuable for the assessment process. Especially in chronic low-dose level exposures, the scientific assessment of related health impairments is often not possible without existing human biomonitoring data. For the future improvement of public health related to poisonings, ingestions by children, workplace chemical exposures, and incidents, we have to establish a nation-wide programme for monitoring human exposures which keeps pace with the progressive production of new chemicals. This must be done in close co-operation with physicians, poison centres, government safety organisations, and environmental health specialists and must be based on proven expert judgement tools and available human biomonitoring data.     

Dermal absorption potential of industrial chemicals: criteria for skin notation

A dermal penetration rate (flux), predicted from physical properties of 132 chemicals, is suggested as an index of the dermal absorption potential of industrial chemicals. The prediction is designed for organic nonelectrolytes. Two reference values are recommended as criteria for skin notation: 1) dermal absorption potential, which relates to dermal absorption raising the dose of nonvolatile chemicals or biological levels of volatile chemicals 30% above those observed during inhalation exposure to TLV-TWA only--dermal absorption of chemicals belonging to this category should be considered when data obtained by biological monitoring are interpreted; and 2) dermal toxicity potential, which relates to dermal absorption that triples biological levels as compared with levels observed during inhalation exposure to TLV-TWA only. Chemicals belonging in this category should carry a skin notation. The toxicity criteria may not be valid for chemicals whose TLVs are based on preventing irritation and discomfort.     

Biomonitoring and biomarkers: exposure assessment will never be the same

Using modern analytical technology, it is now possible to measure almost any chemical present in our bodies. The future role of classical exposure assessment will perhaps be marginalized because biomonitoring programs can directly measure the concentration of chemicals that are present in biologic matrices. Although the concentration of chemicals in the environment will continue to be measured and related to exposure parameters, the prioritization of the national environmental agenda will be dictated by biomonitoring. Recent biomonitoring studies have examined the levels of >200 chemicals. Biomonitoring data, by themselves, are not informative in helping consumers understand their individual health risk. A major challenge facing those who conduct biomonitoring programs is how to best communicate the information to the public. In this article, we review benefits and challenges, along with select results from the Centers for Disease Control and Prevention's 2005 National Report on Human Exposure to Environmental Chemicals. We recommend that these data be carefully interpreted, with the goal of establishing baseline exposure information, rather than creating surrogates for conclusions about human health risk.     

Environmental surveys, specimen bank and health related environmental monitoring in Germany

Production of chemicals, use of products and consumer goods, contamination of food as well as today's living conditions are related to a substantial exposure of humans to chemicals. Safety of human beings and the environment has to be safeguarded by producers and government. Human biomonitoring (HBM) has proven to be a useful and powerful tool to control human exposure and facilitate risk assessment. Therefore, the German Federal Environment Agency (Umweltbundesamt, UBA) employs two major HBM tools, the German Environmental Survey (GerES) and the German Environmental Specimen Bank (ESB). GerES is a nationwide population representative study on HBM and external human exposure, which has, inter alia, been used to identify lead in tap water, lead dustfall, time spent in traffic, and age of dwelling as exposure sources for lead and, thus, to derive risk reduction measures. The ESB is a permanent monitoring instrument and an archive for human specimens. Retrospective monitoring of phthalates and bisphenol A provides a continuous historical record of human exposure in Germany, over the last decades. Additionally it revealed that estimations of human exposure based on production and consumption data may supply misleading information on human exposure. HBM data demonstrated that (a) the use if the restricted isomer di-n-butylphthalat decreased while di-i-butylphthalate levels remained constant and (b) human bisphenol A exposure might be overestimated without monitoring data. The decrease of polycyclic aromatic hydrocarbon-exposure proves the success of German environmental policy after German re-unification. In addition to GerES and ESB UBA is involved in different co-operation networks, the two most prominent of which are (1) the harmonization of HBM in Europe (ESBIO; Expert Team to Support Biomonitoring in Europe, COPHES/DEMOCOPHES; Consortium to Perform Human Biomonitoring on a European Scale/Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) and (2) the co-operation between BMU and the German Chemical Industry Association (VCI). In the latter project emphasis will be placed on substances with a potential relevance for health and on substances to which the general population might potentially be exposed to a considerable extent and for which HBM methods are not available up to now.     

Children's exposure assessment: a review of factors influencing Children's exposure, and the data available to characterize and assess that exposure

We review the factors influencing children's exposure to environmental contaminants and the data available to characterize and assess that exposure. Children's activity pattern data requirements are demonstrated in the context of the algorithms used to estimate exposure by inhalation, dermal contact, and ingestion. Currently, data on children's exposures and activities are insufficient to adequately assess multimedia exposures to environmental contaminants. As a result, regulators use a series of default assumptions and exposure factors when conducting exposure assessments. Data to reduce uncertainty in the assumptions and exposure estimates are needed to ensure chemicals are regulated appropriately to protect children's health. To improve the database, advancement in the following general areas of research is required: identification of appropriate age/developmental benchmarks for categorizing children in exposure assessment; development and improvement of methods for monitoring children's exposures and activities; collection of activity pattern data for children (especially young children) required to assess exposure by all routes; collection of data on concentrations of environmental contaminants, biomarkers, and transfer coefficients that can be used as inputs to aggregate exposure models.     

Human reproduction and environmental risk factors

Environmental pollution is a great cause of concern, in particular, growing attention is being paid to the potential of many chemicals to affect the reproductive system in humans. The key role of prevention and control of reproductive hazards is recognized world-wide. Many chemicals have been shown to impair fertility and/or prenatal and perinatal development in experimental studies. However, a sufficient evidence of an effect on human reproduction is available for some compounds only. The use of biological markers may improve the assessment of exposure to chemicals, contribute to identify mechanisms of action and put into evidence early, reversible, biological effects. Valid biological markers are also needed in epidemiological studies: without reliable data on the level of current and past exposures it is difficult to establish a causal relationship between a pollutant and the occurrence of adverse health effects. A multidisciplinary approach to risk assessment is required. Priorities for interdisciplinary research on environmental chemicals and reproduction include the identification of susceptible population subgroups and risk assessment of exposure to multiple chemicals.     

Interactions between alcohol and work exposure to chemical substances

BACKGROUND AND OBJECTIVES: The quite diffused habit of a significant assumption of alcohol drinks, can interfere with the professional exposure to chemical substances. The interaction may result in increasing their toxicity and/or modifying the parameters of the biological monitoring. It may also act as a confounding factor, not only in epidemiologic researches but also at individual level when the assessment of the occupational exposure and/or the diagnosis of an occupational diseases, is under consideration. We review available references in the literature summarizing major scientific evidences. RESULTS: The interaction between the alcohol assumption and industrial chemicals may be toxicokinetic or toxicodynamic. Alcohol can interfere in the processes of biotransformation of xenobiotics and modify the doses and the effect indicators used for the biological monitoring, causing wrong interpretations of the results. The metabolism of ethanol can be altered by the exposures to toxic industrial materials, creating some clinical pictures of alcohol intolerance, like an "antabuse syndrome" or an "degreaser flush syndrome". Professional exposure to carbon sulfide or to dimethylformamides, trichloroethylene as well as to nitroglycerin and nitroglycole ethylenic can produce similar syndromes. Interactions are reported between alcohol and solvents: on toxicokinetic bases for methanol, isopropanol, glycol ether, trichloroethylene, methyl ethyl ketone and toluene; and on toxicodynamic bases for CNS. Also between alcohol and metals there can occur toxicokinetic interactions, like in the case of lead and mercury. Alcohol can also interfere with the biological monitoring of solvents, producing an over-estimation of the exposure. CONCLUSIONS: For the biological monitoring of reported chemical substances, it is suitable to evaluate the biologic indicators in the days in which there is not assumed alcohol. If this cannot be guaranteed, it is necessary to know at least the quantity of the alcohol consumed or at least if the subject is an alcohol abuser.     

Human biomonitoring assessment values: Approaches and data requirements

Human biomonitoring (HBM) data is a very useful metric for assessing human's exposures to chemicals in commerce. To assess the potential health risks associated with the presence of chemicals in blood, urine or other biological matrix requires HBM assessment values. While HBM assessment values based on human exposure–response data remain the most highly valuable and interpretable assessment values, enough data exists for such values for very few chemicals. As a consequence, efforts have been undertaken to derive HBM assessment values in which external dose based guidance values such as tolerable daily intakes have been translated into equivalent biomonitoring levels. The development of HBM values by the German HBM Commission and Biomonitoring Equivalents by Summit Toxicology has resulted in conceptually similar assessment values. The review of the development of these values provided here demonstrates examples and approaches that can be used to broaden the range of chemicals for which such assessment values can be derived. Efforts to date have resulted in the publication of HBM assessment values for more than 80 chemicals, and now provide tools that can be used for the evaluation of HBM data across chemicals and populations.     

Improved use of workplace exposure data in the regulatory risk assessment of chemicals within Europe

The process of risk assessment for human health demands the availability of soundly based effects and exposure information. However, many of the available data, particularly those which seek to describe human exposures to chemicals, are of varying quality and scope. Changing public and regulatory expectations increasingly demand that the outcomes of risk assessments are seen to have duly accounted for these data, in order that their conclusions can be viewed as valid. The challenge for risk assessors, therefore, is how the different grades of data should be integrated within the overall process. A series of core values are identified that govern the relationships and the influence that different types of exposure data have within European Union (EU) regulatory risk assessment for chemicals. Building on these values, an approach is presented for evaluating workplace exposure information in the context of how such data might be used within the EU process for assessing the risks to human health of new and existing substances. The implications of adopting the approach for regulatory risk assessment within the EU and its consequent impact on current occupational hygiene practice are discussed.     

The bioavailability of chemicals in soil for earthworms

The bioavailability of chemicals to earthworms can be modified dramatically by soil physical/chemical characteristics, yet expressing exposure as total chemical concentrations does not address this problem. In order to understand the effects of modifying factors on bioavailability, one must measure and express chemical bioavailability to earthworms in a consistent, logical manner. This can be accomplished by direct biological measures of bioavailability (e.g., bioaccumulation, critical body residues), indirect biological measures of bioavailability (e.g., biomarkers, reproduction), or indirect chemical measures of bioavailability (e.g., chemical or solid-phase extracts of soil). If indirect chemical measures of bioavailability are to be used, they must be correlated with some biological response. Bioavailability can be incorporated into ecological risk assessment during risk analysis, primarily in the estimation of exposure. However, in order to be used in the site-specific ecological risk assessment of chemicals, effects concentrations must be developed from laboratory toxicity tests based on exposure estimates utilizing techniques that measure the bioavailable fraction of chemicals in soil, not total chemical concentrations.     

Application of human biomonitoring (HBM) of chemical exposure in the characterisation of health risks under REACH

REACH requires health risk management for workers and the general population and introduced the concept of Derived No-Effect Level (DNEL). DNELs must be derived for all substances that are classified as hazardous. In analogy to other health-risk based guidance values, such as reference doses (RfDs) and tolerable daily intakes (TDIs), risk to health is considered negligible if the actual exposure is less than the DNEL. Exposure assessment is relatively simple for occupational situations but more complex for the general public, in which exposure may occur via multiple pathways, routes, and media. For such complex or partially defined exposure scenarios, human biomonitoring (HBM) gives a snapshot of the internal or absorbed dose of a chemical and is often the most reliable exposure assessment methodology. For human risk management, HBM data can be interpreted using the recently developed concept of Biomonitoring Equivalents (BEs). Basically, a BE translates an established reference value into a biomarker concentration using toxicokinetic data. If the results of an exposure assessment using HBM indicate that the levels measured are below the DNEL-based BE (BE(DNEL)), it would indicate that the combined exposure via all potential exposure routes is unlikely to pose a risk to human health and that health risk management measures might not be needed. Hence, BEs do not challenge existing risk assessments but rather build upon them to help risk management, the ultimate goal of any risk assessment. A challenge in implementing this approach forms the limited availability of toxicokinetic information for many substances. However, methodologies such as generic physiologically based toxicokinetic models, which allow estimation of biomarker concentrations based on physicochemical properties, are being developed for less data-rich chemicals. Acceptance of the use of BE by regulatory authorities will allow initial screening of population exposure to chemicals to identify those chemicals requiring more detailed risk and exposure assessment, assisting in priority setting and ultimately leading to improved product stewardship and risk management.     

A questionnaire survey on the dissemination of personal exposure monitoring of organic solvents in Japan

A questionnaire survey on the dissemination of personal exposure monitoring of hazardous chemicals, especially organic solvents, was conducted on 404 Japanese institutions for occupational health and environment, including enterprises, national and municipal institutes, universities and colleges. Responses were received from 236 organizations. The results can be summarized as follows: Of the 236 organizations which responded, 89 (37.7%) had some experience in measuring personal exposure in workers exposed to hazardous chemicals. In 74.2% of these 89 institutions, personal exposure monitoring of organic solvents was being made. Passive dosimeter method was far more commonly employed in Japan than charcoal tube method. Personal exposure measurement is predominantly regarded to be supplementary to the general air sampling and measurement method provided for in the Working Environment Measurement Law (1975). It is considered that personal exposure monitoring would be further disseminated in Japan than today with the aim of improving the health care system for industrial workers and of elucidating epidemiologically the relationship of chemical exposure to biological effects.