ECHA Scientific report for evaluation of limit values for cadmium and its inorganic compounds at the workplace Prepared by the European Chemicals Agency 14 September 2020 Telakkakatu 6, P.O. Box 400, FI-00121 Helsinki, Finland | Tel. +358 9 686180 | Fax +358 9 68618210 | echa.europa.eu ECHA SCIENTIFIC REPORT ON CADMIUM AND ITS INORGANIC COMPOUNDS II Preamble The Commission, in view of the preparation of the fifth proposal for amendment of Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work (CMD), and in line with the 2017 Commission Communication ‘Safer and Healthier Work for All’ - Modernisation of the EU Occupational Safety and Health Legislation and Policy1, asked the advice of RAC to assess the scientific relevance of occupational exposure limits for some carcinogenic chemical substances. Therefore, the Commission made a request on 08/01/2020 to ECHA in accordance with the Service Level Agreement (SLA) (Ares(2019)18725), to evaluate, in accordance with the Directive 2004/37/EC, the following chemical compound(s): cadmium and its inorganic compounds. In support of the Commission’s request, ECHA has prepared a scientific report concerning occupational limit values for cadmium and its inorganic compounds at the workplace. In the preparatory phase of making this report, a call for evidence was started on 02/03/2020 to invite interested parties to submit comments and evidence on the subject by 02/06/2020. The evidence collected was made publicly available at: https://echa.europa.eu/oels-cce-current-consultation. The scientific report was made publically available at: https://echa.europa.eu/oels-pc-on-oel-recommendation on 14/09/2020 and interested parties were invited to submit comments by 12/11/2020. The Committee for Risk Assessment (RAC) will develop its opinion on the basis of the scientific report submitted by ECHA. During the preparation of the opinion on occupational limit values for cadmium and its inorganic compounds, the scientific report will be further developed as the Annex to the RAC opinion. Following adoption of an opinion on cadmium and its inorganic compounds, recommending an Occupational Exposure Limit for cadmium and its inorganic compounds by RAC, the Annex will be amended to align it appropriately with the view of RAC. It supports the opinion of the RAC and gives the detailed grounds for the opinion2. 1 http://ec.europa.eu/social/main.jsp?langId=en&catId=148&newsId=2709&furtherNews=yes 2 https://echa.europa.eu/documents/10162/13579/interim_wponevaluation_oel_agreed_rac_42_en. pdf/021bc290-e26c-532f-eb3f-52527700e375 Telakkakatu 6, P.O. Box 400, FI-00121 Helsinki, Finland | Tel. +358 9 686180 | Fax +358 9 68618210 | echa.europa.eu ECHA SCIENTIFIC REPORT ON CADMIUM AND ITS INORGANIC COMPOUNDS III Table of Contents SCOPE OF THE TASK AND LITERATURE SEARCH .................................................... 7 RECOMMENDATION ............................................................................................ 7 1. CHEMICAL AGENT IDENTIFICATION AND PHYSICO-CHEMICAL PROPERTIES .......... 8 2. EU HARMONISED CLASSIFICATION AND LABELLING - CLP (EC) 1272/2008 ........... 10 3. CHEMICAL AGENT AND SCOPE OF LEGISLATION - REGULATED USES OF CADMIUM AND ITS INORGANIC COMPOUNDS IN THE EU ....................................................... 13 DIRECTIVE 98/24/EC AND DIRECTIVE 2004/37/EC ....................................... 13 REACH REGISTRATIONS ............................................................................ 13 AUTHORISED USES UNDER ANNEX XIV OF REACH ........................................ 14 RESTRICTED USES UNDER ANNEX XVII OF REACH ....................................... 14 3.4.1 Other EU restrictions ........................................................................ 15 PLANT PROTECTION PRODUCTS REGULATION (EC) 1107/2009 ...................... 15 HUMAN AND VETERINARY MEDICINAL PRODUCTS DIRECTIVES 2001/83/EC AND 2004/28/EC RESPECTIVELY ................................................................... 15 BIOCIDAL PRODUCTS REGULATION (EU) 528/2012 ...................................... 15 4. EXISTING OCCUPATIONAL EXPOSURE LIMITS .................................................... 15 5. OCCURRENCE, USE AND OCCUPATIONAL EXPOSURE .......................................... 19 OCCURRENCE ........................................................................................... 19 OCCUPATIONAL EXPOSURE ........................................................................ 19 PRODUCTION AND USE INFORMATION ........................................................ 19 ROUTES OF EXPOSURE AND UPTAKE ........................................................... 25 5.4.1 Worker exposure .............................................................................. 25 5.4.2 General population ........................................................................... 25 6. MONITORING EXPOSURE ................................................................................. 26 EXTERNAL EXPOSURE ............................................................................... 26 BIOMONITORING OF EXPOSURE (INTERNAL EXPOSURE) ............................... 27 6.2.1 Background levels ............................................................................ 27 6.2.2 Biomonitoring analytical methods ....................................................... 27 7. HEALTH EFFECTS ........................................................................................... 28 TOXICOKINETICS (ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION - ADME) ................................................................................................ 28 7.1.1 Human data .................................................................................... 28 7.1.2 Animal data ..................................................................................... 29 7.1.3 In vitro data .................................................................................... 29 IV ECHA SCIENTIFIC REPORT ON CADMIUM AND ITS INORGANIC COMPOUNDS 7.1.4 Toxicokinetic modelling ..................................................................... 29 7.1.5 Biological monitoring ........................................................................ 30 7.1.6 Summary ........................................................................................ 31 ACUTE TOXICITY ...................................................................................... 31 7.2.1 Human data .................................................................................... 31 7.2.2 Animal data ..................................................................................... 32 7.2.3 Summary ........................................................................................ 33 SPECIFIC TARGET ORGAN TOXICITY/REPEATED DOSE TOXICITY .................... 33 7.3.1 Human data .................................................................................... 33 7.3.2 Animal data ..................................................................................... 39 7.3.2.1 Inhalation ............................................................................. 39 7.3.2.2 Oral exposure ....................................................................... 39 7.3.2.3 Dermal exposure ................................................................... 40 7.3.3 In vitro data .................................................................................... 40 7.3.4 Summary ........................................................................................ 40 IRRITANCY AND CORROSIVITY ................................................................... 40 7.4.1 Human data .................................................................................... 40 7.4.2 Animal data ..................................................................................... 40 7.4.2.1 Skin ..................................................................................... 40 7.4.2.2 Eyes .................................................................................... 40 7.4.3 In vitro data .................................................................................... 41 7.4.4 Summary ........................................................................................ 41 SENSITISATION ....................................................................................... 41 7.5.1 Human data .................................................................................... 41 7.5.2 Animal data ..................................................................................... 41 7.5.1 In vitro data .................................................................................... 41 7.5.2 Summary ........................................................................................ 41 GENOTOXICITY ........................................................................................ 41 7.6.1 Human data .................................................................................... 41 7.6.2 Animal data ..................................................................................... 42 7.6.3 In vitro data .................................................................................... 43 7.6.4 Summary ........................................................................................ 43 CARCINOGENICITY ................................................................................... 43 7.7.1 Human data ...................................................................................