Five chemicals used in workplace, for which a risk assessment had already been carried out, were selected and the relevant critical studies re-analyzed by the Benchmark approach. The endpoints involved included continuous, and ordinal data. Dose-response modeling could be reasonablyapplied to the dose-response data encountered, and Critical Effect Doses (CEDs) could be derived for almost all of the endpoints considered. The resulting benchmark dose for the study as a whole was close to the NOAEL in two cases, and higher than the LOAEL in two other cases where no NOAEL could be derived. In the fifth case the dose-response data were considered inconclusive after analysis by the Benchmark approach, making the choice of the study involved as the critical study doubtful.It is concluded that the Benchmark approach appears applicable to OECD toxicity studies, if at least two dose groups with (different) effects are observed. In situations where only one dose group shows effects the benchmark approach does not offer much of an improvement over the NOAEL approach. However, the situation that bserved effects are not replicated in other dose groups may give unreliable results whatever approach used, including the NOAEL approach. A single significantly different dose group could be the result of some unknown experimental factor otherthan the applied dose, and therefore replication of effects in different dose groups is a prerequisite, whatever method of analysis is used. The re-analysis of the five compounds selected illustrates that the Benchmark approach helps in getting a more complete view of the toxicity of the compound, if effects at different levels are observed in different dose groups.

This report is produced in the framework of EUBEES (EU working group on Gathering, Review and Development of Environmental Emission Scenarios for Biocides). It contains a proposal that is aimed at obtaining a uniform definition of symbols, in order to make emission scenario documents (ESDs) better readable and comparable. It fits in with the lists of symbols as present in EUSES and USES (in both cases Appendix II). Furthermore, the implementation in EUSES will become easier. In the European Union System for the Evaluation of Substances (EUSES) and the Dutch Uniform System for the Evaluation of Substances (USES) hundreds of symbols are used for all parameters and variables. In the ESDs (Emission Scenario Documents) that have been developed in the European Union so far, also many parameters and variables occur. These parameters and variables are often specific for one scenario, while others occur in EUSES, USES or other ESDs. The symbols used in the ESDs differ in many cases from document to document. Therefore, it is desirable that new ESDs should use the variable names and units already existing. For new parameters the same formats should be used as described in this report.

This report is an update of previous guidance documents for deriving environmental risk limits in the Netherlands. The updated methodology to derive risk limits for water, groundwater, soil, sediment and air and their harmonisation is presented. The document covers the derivation of the Serious Risk Concentration (SRC), the Maximum Permissible Concentration (MPC) and the Negligible Concentration (NC).

Quantitative Structure Activity Relationship (QSAR) modelling techniques are overviewed here, along with descriptors which can be used in QSAR equations and the different statistical methods suitable for deriving QSARs. Discussed is the current state of the art on the use of QSAR estimates within the different regulatory assessment frameworks of the Centre for Substances and Risk Assessment at the Dutch National Institute of Public Health and the Environment (RIVM/CSR). Special emphasis has been placed on environmental effect assesssments. Commonly accepted QSAR equations and software programs used in environmental exposure assessments are described. Generally accepted QSAR equations and other QSARs for environmental effects documented in the literature are presented in tabular form; compounds acting by non-polar narcosis, polar narcosis, reactive chemicals and chemicals with a specific mode of action are presented separately. Recently developed computerised QSAR programs are also overviewed. Several recommendations are made for the use of QSARs within RIVM/CSR risk/hazard assessment frameworks, with experiences related to routine application of QSARs in effect assessments to be evaluated and reported on within one year.

This report describes a proposal for the procedures for setting an Acute Reference Dose (ARfD) for pesticides evaluated in the Netherlands. This deals with both evaluations on the national level (on behalf of the Dutch Board for the Authorisation of Pesticides (CTB)) and evaluations at the European level (EU-monographs), either made within the scope of the Pesticide Act ("Bestrijdingsmiddelenwet" BMW) or the EU Directive 91/414. Subjects covered by this report are: a definition of the concept of the ARfD, criteria for setting an ARfD, the relevance of effects for an ARfD, the use of assessment factors. In addition, a fututre outlook is presented on developments in the field of risk assessment for acute exposure to pesticides.

In this report an overview is given of structure-activity relationships (SARs) described in literature that can be helpful for the daily human hazard evaluation of chemicals. SARs describe the relation between molecular structure and biological- or physical-chemical activity of the chemical. Chemicals that share structural features are presented that can have an effect on the toxicological endpoints: irritation, sensitisation, neurotoxicity (acetylcholinesterase-inhibition), genotoxicity and reproductive and developmental. These SARs were discussed in a Workshop. The results of this Workshop, which was attended by RIVM and TNO risk assessors and experts, are presented also. One of the results is a list of structural features with possible effects on the above mentioned toxicological endpoints. It is proposed to test these SARs in the next two years on chemicals for which experimental data are available. This report may help to increase the quality of the hazard assessment.

On May 13, 2000 the city of Enschede was hit by a series of explosions in a fireworks storage depot in the middle of a residential city district. The explosions resulted in a huge fire, in which more than 200 dwellings and dozens of commercial buildings were damaged. As a result of the accident, 22 people died and more than 1000 were wounded. On the day of the fire and the days following, RIVM's Environmental Incident Service took a series of samples in the surroundings of the fire to determine the potential exposure of the people involved. Measurements in the smoke, close to the fire, showed high concentrations of particles, carbon monoxide and heavy metals, especially lead, copper and zinc. In a second series of measurements made on the days following the fire only slightly increased concentrations of particles, heavy metals, volatile organic compounds and dioxins were found. Outside the measurement area background concentrations were hardly, if at all, exceeded. Concentrations of asbestos in the air did not exceed the maximum risk level. The data were used to estimate the potential human exposure to toxic compounds on the basis of exposure profiles of the people involved. The estimated exposure was compared to health based guidelines and it was concluded that health effects due to the exposure were highly unlikely, with the exception of short-term irritation of the air ways. Measurements of deposition showed the environmental load outside the disaster area to be non-relevant with respect to the normal background concentrations in soil.

The current knowledge about the ecological relevance of mutagenic substances is described. Mutations can be divided in somatic and germ-line mutations. Current screening methods in genotoxicology are focussed on the protection of man, and therefore somatic mutations are the most crucial. In the field, these mutations are only a hazard for natural populations of species with a low reproductive output. These species are supposed to be protected by the current screening methods. Germ-line mutations seem to be more relevant for natural populations, but screening on these mutations does not take place in the regular testing of substances. However, the frequency of germ-line mutations is probably much lower. Germ-line mutations can be divided between non-lethal and lethal mutations. Lethal mutations do not pose a risk, as they disappear in the next generation. Non-lethal mutations only pose a risk when genes are affected that influence the fitness of the phenotype negatively. However, the current screening methods for somatic mutations are supposed to act as a safeguard for heritable effects. It is concluded that the methods in the regular hazard assessment of substances likely provide a base for protecting natural populations against mutagenic substances.

In toxicology uncertainty factors are applied to account for differences between experimental animals and humans (interspecies variation) and to account for interindividual variation. Human drug dossiers contain studies on experimental animals as well as on humans. As such, these dossiers may contain valuable information to elucidate interspecies and intraspecies variation. This report shows that there is no adequate information available to study interspecies differences. However, data in human drug dossiers may be valuable for intraspecies comparison. The results favour the distribution of intraspecies variation as proposed by Slob and Pieters in earlier work.

Gepresenteerd worden 8 factsheets voor de risicoschattingsmethoden van het Centrum voor stoffen Risicobeoordeling (CSR) van het Rijksinstituut voor Volksgezondheid en Milieu (RIVM). 5 Factsheets hebben betrekking op de risicoschattingmethoden voor de volksgezondheid en 3 op de risicoschattingsmethoden voor het milieu: 1) Methemoglobine/Heinz bodies, 2) Acetylcholinesterase inhibitors, 3) Pheochromocytomas, 4) Assessment factors for human health risk assessment, 5) Delayed Neurotoxicity/NTE-inhibition, 6) Residues of plant protection products on food items for birds and mammals, 7) Degradation of veterinary drugs in manure, 8) Guideline for the evaluation of studies determining the excretion of veterinary drugs. Naast het vastleggen van de risicoschattingsmethoden zoals die bij het RIVM/CSR worden gehanteerd is het doel van deze publicatie de risicoschattingsmethoden transparanter te maken en een platform voor discussie te creeren. De auteurs van elke factsheet beschrijven de "state-of-the-art" van hun onderwerp. Opmerkingen, tekortkomingen en aanvullende informatie wordt op prijs gesteld en kunnen naar de eerste redacteur worden opgestuurd.