GUIDELINES FOR PREPARING CHEMICALS REVIEWS
1. Review documents and reports on chemicals differ widely in their purpose, format and content. The various reasons for preparing chemicals reviews include:
a) Identifying chemicals for further data development;
b) Reviewing a specific property of a chemical;
c) Supporting decisions to regulate or not to regulate chemicals.
Whatever the ultimate reason for preparing a chemicals review may be, it will generally involve some assessment of the potential hazard of the chemical concerned.
2. These Guidelines are intended to promote the consistent presentation of information in chemicals reviews, which will:
a) Facilitate international use and exchange of chemicals review documents;
b) Provide the reader with an indication of the amount of available information or the lack thereof;
c) Allow the reader to locate information of interest.
The exchange of reviews would avoid duplication of efforts, thereby conserving scarce resources.
3. While these Guidelines are aimed at achieving consistency, flexibility in their application is essential. Since chemicals reviews may be developed for a wide variety of purposes and reflect a broad range of information needs and availability, all reviews will not contain the same data elements. Whether certain data elements are included will also depend on the type of chemical under review.
4. A list of data elements for possible inclusion in chemicals reviews is found in paragraphs 9 through 21.
5. The Guidelines address the following points:
a)Elements to be considered in a chemicals review;
b)Quality of data;
c)Format of review documents.
II. Elements to Consider
6. Prior to the preparation of any review document, it is important to consider the potential hazard of the chemical in order to determine the amount of scrutiny which may be necessary. The selection of data elements to be included in a chemicals review depends upon this preliminary hazard assessment and the importance of the data elements relative to the specific purpose of the review. The depth at which properties of a chemical are reviewed also depends upon the degree of concern derived from the preliminary hazard assessment. Technical knowledge and sound scientific judgement are of importance both in selecting data elements and in determining the depth of the review.
7. A review process usually begins with the gathering of available information. In some cases, sufficient information is available for the preparation of a chemicals review. In other situations, gaps in information elements may be identified.
8. Since the broad dissemination of chemicals reviews is desirable, non-confidential data should be used to the greatest extent possible. Nonetheless, in certain situations the use of confidential data may be unavoidable. This will not necessarily preclude the exchange of review documents. The problems associated with the exchange of confidential information have been addressed by the OECD. Its work resulted in three Recommendations, adopted by the OECD Council in 1983, concerning:
• The Protection of Proprietary Rights to Data Submitted in Notifications of New Chemicals [C(83)96(Final)];
• The Exchange of Confidential Data on Chemicals [C(83)97(Final)];
• The OECD List of Non-Confidential Data on Chemicals [C(83)98 (Final)].
These Recommendations should be taken into account when preparing and exchanging chemicals reviews.
III. Elements for Possible Inclusion in Chemicals Reviews
9. Data elements for possible inclusion in a chemicals review may be categorised in the following way:
10. Under this heading would be included: the purpose of the review, a description of substance(s) reviewed, major findings and deficiencies, a general statement describing whether quality considerations were included, major conclusions, and recommendations (in the national language and a translation into English or French, as appropriate).
11. Under this heading would be found the constituent(s) of product(s) under review including:
a) Primary constituent:
• IUPAC-name (with indication of system used);
• Other names - common, (registered) trade, CAS-name;
• Empirical formula;
• Structural formula (where relevant, isomeric composition);
• Molecular weight;
• Spectral data.
b) Impurities (identity, range of percentage composition);
c) Additives (identity, range of percentage composition).
Physical and Chemical Properties
12. The data included here are those relevant for assessing exposure and effects, such as: physical state (including colour, smell, taste); melting and boiling points; vapour pressure; density; solubility in water and organic solvents; partition co-efficient (specifying solvents pairs used, e.g., n-octanol/water, oil/water, etc.); surface tension; reactivity (e.g. oxidising properties, flammability, explosive properties); soil absorption constant; dissociation constant; Henry's constant; volatility; particle size.
13. Methods used, including media and sampling procedures and preparations, would be given under this heading.
14. The data to be included here are:
a) Those relevant for assessing exposure via the workplace, consumer products or the environment, such as:
• Natural occurence;
• Production volume and trends;
• Consumption, import, export;
• Production process types;
• Handling (including transportation) and distribution aspects;
• Plant releases during manufacture and processing;
• Waste disposal (including incineration);
• Use pattern (types of use, dispersiveness of use, exposed populations and special sub-populations, routes, frequency and duration of exposure).
b) Those relevant for assessing transport, distribution and transformation/degradation in the environment, such as:
• Transport and distribution between different media;
• Biotic and abiotic degradation;
• soil absorption constants;
• Interaction with other physical factors;
• Ultimate fate following use.
c) Those relevant for monitoring data, such as level in air, water, soil/sediments, plants, food, feed, working environment, domestic environment, biological samples and consumer products.
Effects on Experimental Animals and In Vitro Test Systems
15. Data to be included here are those relevant to assessing the metabolism and effects of the chemical, or the lack thereof, on animal and in vitro systems used to model human health, such as:
• Metabolism (absorption, distribution, metabolic transformation, elimination, and retention);
• Acute toxicity, short-term repeated dose toxicity, subchronic toxicity, chronic toxicity, allergenicity, embryotoxicity and teratogenicity, mutagenicity, carcinogenicity; effects on the reproductive system, immune system, nervous system, behaviour, cardiovascular system, hemapoietic system; effects on skin, eye and mucous membranes; organ-specific effects on gastrointestinal tract, kidney, liver, etc.; effect on cellular, sub-cellular and biochemical structures or processes (e.g. DNA damage, cell transformation, clastogenic alterations, enzyme inhibition, etc.); data related to synergistic phenomena or antagonistic effects; and other phenomena which modify the toxicity profile of the chemical (e.g. age, sex, nutritional status).
Effects on Man
16. Data included here are those obtained in observations from exposed persons which are relevant in a hazard evaluation:
a) Studies and observations of:
• Acute toxicity;
• Poisoning incidents;
• Subacute effects;
• Effects of longterm exposure.
b) Epidemiological studies of:
• General populations;
• Sub-populations (samples with reference to age, sex, occupational exposure).
Effects on the Environment
17. Data to be included here are those relevant for estimating the impact on the ecosystem and the bioaccumulation potential, such as toxicity to aquatic organisms, toxicity to terrestrial organisms, toxicity to micro-organisms, effects on ecological processes and biotransformation, population and ecosystem effects, and effects on the abiotic environment.
Other Pertinent Data
18. Data to be included here are those which are not relevant to any other heading but which may be of importance in a hazard evaluation, such as combustion products and transformation products from use or disposal techniques.
Current Regulations, Guidelines and Standards
19. Under this heading would be found: regulations, guidelines, and advice issued by relevant international or national bodies or by the manufacturers.
20. Included here would be:
a) Assessment of exposure;
b) Assessment of health effects;
c) Assessment of environmental effects;
d) Overall assessment of hazards - human health and the environment, general population or ecosystem, special sub-populations or ecosystems (workers, etc., aquatic, terrestrial, etc.) or a more specific part of them (fish, birds, etc.);
e) Gaps in knowledge.
21. A list of sources of data consulted should also be included. Citations should give all information needed to identify and locate each reference.
IV. Quality of Data
22. Confidence in the quality of information used in preparing the review is fundamental to confidence in the conclusions of the review itself. Deficiencies in a certain investigation of a chemical do not preclude the use of that information, but they may reduce confidence in the use of such data for hazard assessment. Nonetheless, the reviewer is often faced with the task of making use of data partly derived from deficient studies.
23. Chemicals reviews are produced for different purposes, and consequently data quality requirements will vary depending on the user's needs. Data which are acceptable to one user under a specific set of conditions may not be acceptable under other circumstances.
24. It is important to inform the reader of the type of criteria and the purpose of the review when selecting, assessing, using and presenting the data. This can be accomplished in two ways: first, by a general statement describing whether quality considerations were included and, if so, the specific methods used to do so; second, by indicating in the report, as far as is practicable, the reasons for selecting key references and excluding others.
25. Assessment of data quality is a process which involves:
a) A review of individual data elements with respect to how the study was conducted and how the results were interpreted;
b) A critical selection (and rejection) of data in its proper context and in accordance with the purpose of the review.
26. Since any information related to toxicological effect or to exposure is potentially useful, general principles for quality assessment should be applied in the review process. Rather than telling the user how "good" or "bad" the data are, such principles should be used to assess the limitations of the data within the context of the user's specific needs.
27. In some cases certain studies (when compared with currently accepted, standardized guidelines) may be regarded as unacceptable. Nevertheless, it should be emphasized that in a specific context such studies contain information which, when viewed together with results from other studies, may be useful. This is particularly important with regard to highly specialised studies intended to resolve specific issues. In such situations, quality standards will be difficult to apply. Such information can be reviewed only on a case-by-case basis and in its proper context.
28. Sound scientific judgement acquired through experience cannot be superseded by any set of general rules for quality evaluation.
29. Current references should be used to assist the reviewer in determining standards for evaluating the quality of individual data elements. Such standards ought to be developed by experts in each individual discipline. In this regard, it should be noted that a great deal of progress has been made and that a number of references are available to guide the reviewer.
30. In evaluating the quality of data in a particular study, the reviewer should take into account other contemporary studies of similar design to that of the study under review. It is obvious that the reviewer cannot control the conduct of reported studies. Moreover, the information available to the reviewer is rarely sufficient to assess how well a study was conducted. On the other hand, serious deficiencies in description of design, procedures used for generating the data, and reporting of results may suggest that important aspects of the conduct of the study have been neglected. It is in this context that the reviewing of other contemporary studies of similar design is desirable.
31. If a study fails to meet modern requirements, it may still satisfy some less rigorous minimum requirements and be judged of sufficient quality to be useful in a review. For certain specific review purposes, it may therefore be useful to develop such minimum standards.
V. Format of Review Documents
32. The review document should begin with a brief executive summary highlighting the purpose of the review, a description of substances reviewed, major findings and deficiencies, a general statement describing whether quality considerations were included, and major conclusions and recommendations. At the end of the document there should be a list of sources of data consulted in the preparation of the review.
33. Closely related types of data can be grouped together in various ways to form separate data categories or information clusters. The data elements in the review should be presented in the sequence set out in paragraphs 9 through 21 above.
34. The review document should give information about the purpose for which it was prepared. Such information allows the reader to evaluate the relevance of the review to his particular needs.
35. The title, tables and diagrams contained in the review, as well as the executive summary, should be presented in one of the OECD languages, that is, in English or French.
36. It should be assumed that if a data element has not been included in the review, it has not been searched for. If a data element has been searched for and not found, this should be indicated. When data are searched for and found, but not included (e.g. for reasons of data quality, confidentiality or irrelevance), this should also be indicated.