N,N-DIMETHYLFORMAMIDE - WHO

1 This report contains the collective views of an international group of experts and does notnecessarily represent the decisions or the stated policy of the United Nations EnvironmentProgramme, the International Labour Organization, or the World Health International Chemical Assessment Document 31N,N-DIMETHYLFORMAMIDEP lease note that the layout and pagination of this pdf file are not identical to those of theprinted CICADF irst draft prepared byG. Long and Meek, Environmental Health Directorate, Health Canada, andM. Lewis, Commercial Chemicals Evaluation Branch, Environment CanadaPublished under the joint sponsorship of the United Nations Environment Programme, theInternational Labour Organization, and the World Health Organization, and produced within theframework of the Inter-Organization Programme for the Sound Management of Health OrganizationGeneva, 2001 The International Programme on Chemical Safety (IPCS), established in 1980, is a joint ventureof the United Nations Environment Programme (UNEP), the International Labour Organization (ILO),and the World Health Organization (WHO).

2 The overall objectives of the IPCS are to establish thescientific basis for assessment of the risk to human health and the environment from exposure tochemicals, through international peer review processes, as a prerequisite for the promotion of chemicalsafety, and to provide technical assistance in strengthening national capacities for the sound managementof Inter-Organization Programme for the Sound Management of Chemicals (IOMC) wasestablished in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO,the United Nations Industrial Development Organization, the United Nations Institute for Training andResearch, and the Organisation for Economic Co-operation and Development (ParticipatingOrganizations), following recommendations made by the 1992 UN Conference on Environment andDevelopment to strengthen cooperation and increase coordination in the field of chemical safety.

3 Thepurpose of the IOMC is to promote coordination of the policies and activities pursued by the ParticipatingOrganizations, jointly or separately, to achieve the sound management of chemicals in relation to humanhealth and the Library Cataloguing-in-Publication DataN,N- dimethylformamide .(Concise international chemical assessment document ; 31) - toxicity assessment Programme on Chemical Safety 92 4 153031 6 (NLM Classification: QV 633) ISSN 1020-6167 The World Health Organization welcomes requests for permission to reproduce or translate itspublications, in part or in full. Applications and enquiries should be addressed to the Office of Publications,World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information onany changes made to the text, plans for new editions, and reprints and translations already available. World Health Organization 2001 Publications of the World Health Organization enjoy copyright protection in accordance with theprovisions of Protocol 2 of the Universal Copyright Convention.

4 All rights designations employed and the presentation of the material in this publication do not imply theexpression of any opinion whatsoever on the part of the Secretariat of the World Health Organizationconcerning the legal status of any country, territory, city, or area or of its authorities, or concerning thedelimitation of its frontiers or mention of specific companies or of certain manufacturers products does not imply that they areendorsed or recommended by the World Health Organization in preference to others of a similar naturethat are not mentioned. Errors and omissions excepted, the names of proprietary products aredistinguished by initial capital Federal Ministry for the Environment, Nature Conservation and Nuclear Safety, Germany,provided financial support for the printing of this by Wissenschaftliche Verlagsgesellschaft mbH, D-70009 Stuttgart 10iiiTABLE OF AND PHYSICAL/CHEMICAL in workplace and metabolites in biological OF HUMAN AND ENVIRONMENTAL TRANSPORT, DISTRIBUTION.

5 AND water and and 9 LEVELS AND HUMAN water and and of the general KINETICS AND METABOLISM IN LABORATORY ANIMALS in human relevant ON LABORATORY MAMMALS AND IN VITRO TEST and 17 Concise International Chemical Assessment Document exposure and and related on ON on the ON OTHER ORGANISMS IN THE LABORATORY AND Evaluation of health 33 identification and dose response in in experimental 33 for setting tolerable concentrations or guidance 33 risk and degree of confidence in human health risk Evaluation of environmental assessment environmental risk of EVALUATIONS BY INTERNATIONAL 38 APPENDIX 1 SOURCE 47 APPENDIX 2 CICAD PEER 47 APPENDIX 3 CICAD FINAL REVIEW 48 APPENDIX 4 BENCHMARK DOSE 49 INTERNATIONAL CHEMICAL SAFETY 50R SUM D 52 RESUMEN DE ORIENTACI 54N,N-Dimethylformamide1 FOREWORDC oncise International Chemical AssessmentDocuments (CICADs) are the latest in a family ofpublications from the International Programme onChemical Safety (IPCS) a cooperative programme ofthe World Health Organization (WHO), the InternationalLabour Organization (ILO), and the United NationsEnvironment Programme (UNEP).

6 CICADs join theEnvironmental Health Criteria documents (EHCs) asauthoritative documents on the risk assessment Chemical Safety Cards on therelevant chemical(s) are attached at the end of theCICAD, to provide the reader with concise informationon the protection of human health and on emergencyaction. They are produced in a separate peer-reviewedprocedure at IPCS. They may be complemented byinformation from IPCS Poison Information Monographs(PIM), similarly produced separately from the are concise documents that provide sum-maries of the relevant scientific information concerningthe potential effects of chemicals upon human healthand/or the environment. They are based on selectednational or regional evaluation documents or on existingEHCs. Before acceptance for publication as CICADs byIPCS, these documents undergo extensive peer reviewby internationally selected experts to ensure theircompleteness, accuracy in the way in which the originaldata are represented, and the validity of the primary objective of CICADs is characteri-zation of hazard and dose response from exposure to achemical.

7 CICADs are not a summary of all available dataon a particular chemical; rather, they include only thatinformation considered critical for characterization of therisk posed by the chemical. The critical studies are,however, presented in sufficient detail to support theconclusions drawn. For additional information, thereader should consult the identified source documentsupon which the CICAD has been to human health and the environment willvary considerably depending upon the type and extentof exposure. Responsible authorities are stronglyencouraged to characterize risk on the basis of locallymeasured or predicted exposure scenarios. To assist thereader, examples of exposure estimation and riskcharacterization are provided in CICADs, wheneverpossible. These examples cannot be considered asrepresenting all possible exposure situations, but areprovided as guidance only. The reader is referred to EHC1701 for advice on the derivation of health-basedtolerable intakes and guidance every effort is made to ensure that CICAD srepresent the current status of knowledge, new informa-tion is being developed constantly.

8 Unless otherwisestated, CICADs are based on a search of the scientificliterature to the date shown in the executive summary. Inthe event that a reader becomes aware of new informa-tion that would change the conclusions drawn in aCICAD, the reader is requested to contact IPCS to informit of the new flow chart shows the procedures followed toproduce a CICAD. These procedures are designed totake advantage of the expertise that exists around theworld expertise that is required to produce the high-quality evaluations of toxicological, exposure, and otherdata that are necessary for assessing risks to humanhealth and/or the environment. The IPCS Risk Assess-ment Steering Group advises the Co-ordinator, IPCS, onthe selection of chemicals for an IPCS risk assessment,whether a CICAD or an EHC is produced, and whichinstitution bears the responsibility of the documentproduction, as well as on the type and extent of theinternational peer first draft is based on an existing national,regional, or international review.

9 Authors of the firstdraft are usually, but not necessarily, from the institutionthat developed the original review. A standard outlinehas been developed to encourage consistency in first draft undergoes primary review by IPCS andone or more experienced authors of criteria documents inorder to ensure that it meets the specified criteria draft is then sent to an international peerreview by scientists known for their particular expertiseand by scientists selected from an international rostercompiled by IPCS through recommendations from IPCS national Contact Points and from IPCS ParticipatingInstitutions. Adequate time is allowed for the selectedexperts to undertake a thorough review. Authors arerequired to take reviewers comments into account andrevise their draft, if necessary. The resulting second draft1 International Programme on Chemical Safety (1994)Assessing human health risks of chemicals: derivationof guidance values for health-based exposure , World Health Organization (EnvironmentalHealth Criteria 170).

10 Concise International Chemical Assessment Document 312 SELECTION OF HIGH QUALITYNATIONAL/REGIONALASSESSMENT DOCUMENT(S)CICAD PREPARATION FLOW CHARTFIRST DRAFTPREPAREDREVIEW BY IPCS CONTACT POINTS/SPECIALIZED EXPERTSFINAL REVIEW BOARD 2 FINAL DRAFT 3 EDITINGAPPROVAL BY DIRECTOR, IPCSPUBLICATIONSELECTION OF PRIORITY CHEMICAL1 Taking into account the comments from The second draft of documents is submitted to the Final Review Board together with the reviewers Includes any revisions requested by the Final Review OF COMMENTS (PRODUCER/RESPONSIBLE OFFICER),PREPARATIONOF SECOND DRAFT 1 PRIMARY REVIEW BY IPCS (REVISIONS AS NECESSARY)N,N-Dimethylformamide3is submitted to a Final Review Board together with thereviewers consultative group may be necessary to adviseon specific issues in the risk assessment CICAD Final Review Board has severalimportant functions: to ensure that each CICAD has been subjected toan appropriate and thorough peer review; to verify that the peer reviewers comments havebeen addressed appropriately; to provide guidance to those responsible for thepreparation of CICADs on how to resolve anyremaining issues if, in the opinion of the Board, theauthor has not adequately addressed all commentsof the reviewers; and to approve CICADs as international members serve in their personal capacity, not asrepresentatives of any organization, government, orindustry.