Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 931-297-3 | CAS number: -
For delineating occupational exposure limits a read across to HDI oligomers, isocyanurate type (EC 931 -274 -8) is applied. This substance is a close structural analogue to HDI oligomers, iminooxadiazindione type, also derived from catalytic oligomerisation of 1,6 -hexamethylene diisocyanate (HDI; CAS 822 -06 -0) and also belonging to the CAS number 28182 -81 -2 (Hexane, 1,6 -diisocyanato-, homopolymer). The read across is based on physicochemical and toxicological similarity. In fact, comparison of the toxicological endpoints, that are available for both of the two substances reveal good correlation.
With respect to Inhalation Toxicity an expert statement is available justifying the read across (Pauluhn, Comparison of pulmonary irritation potency..., Bayer HealthCare AG, 2008; attached to this endpoint summary).
Therefore, test results obtained for HDI oligomers, isocyanurate type can be transferred to HDI oligomers, iminooxadiazindione type and the DNELs delineated for HDI oligomers, isocyanurate type are also valid for HDI oligomers, iminooxadiazindione type. This approach is in accordance with Annex XI, section 1.5 of the REACH Regulation (Regulation (EC) No 1907/2006).
For workers in industrial settings, which are exposed via inhalation, DNELs for local effects for acute and long-term inhalation exposure have to be derived. In addition, sensitisation after skin contact has to be assessed.
According to Guidance Document R.8 (ECHA, 2012) a national occupational exposure limit (OEL) could be used as a surrogate for a DNEL. The German Federal Ministry of Labour and Social Affairs (Bundesministerium für Arbeit und Soziales, BMAS) published the Technical Rule for Hazardous Substances 430 (TRGS 430, last updated in 2009) for regulating the workplace exposure of isocyanates. ”This technical rule describes procedures for the assessment and surveillance of workplaces involved in the handling and use of polyurethanes and requires the assessment of isocyanates present either in the form of vapour, aerosol or both” (Pauluhn, J. Appl. Toxicol., 24, 2004, 231-247). In contrast to commonly employed workplace standards that focus solely on monomeric (di)isocyanates, the common unifying concept of TRGS 430 is to consider separate hazard assessment for monomeric and polymeric isocyanates, present as vapour and/or aerosol.
The surrogate now used as DNEL for HDI oligomers, iminooxadiazindione type is the exposure assessment value (Expositionsbeurteilungswert, EBW). The EBW is either derived from the acute pulmonary irritant threshold concentration using a benchmark extrapolation of the concentration dependence of protein in bronchoalveolar lavage fluid of an 1 x 6 hours inhalation study (study recommended in TRGS 430) or, alternatively, if available, from the NOAEC of a subchronic (13-week) inhalation study according to OECD 413 or OPPTS 870.3465. The approach suggested by TRGS 430 is inherently conservative, as a comparison of the irritant threshold concentration to the NOAEC from repeated inhalation studies show (Pauluhn, J. Appl. Toxicol., 24, 2004, 231-247).
If the irritant threshold concentration/NOAEC of the polymeric diisocyante from either of the two studies is ≤10 * AGW (Arbeitsplatzgrenzwert = German national OEL) of the monomeric diisocyanate then EBW = AGW, if the threshold concentration is > 10 * AGW then EBW = 10 * AGW.
For the monomeric hexamethylen-1,6-diisocyante (HDI) the AGW is 0.035 mg/m³. Since for HDI oligomers, iminooxadiazindione type the pulmonary irritant threshold concentration (2.1 mg/m³; report no. AT01058, Bayer AG, 2004) is > 10 * AGW the EBW = 10 * AGW. The data for the read-across substance support this, as for HDI oligomers, isocyanurate type both the pulmonary irritant threshold concentration as well as the derived no observed adverse effect concentration of the subchronic study are > 10 * AGW (3 mg/m³, report AT03922, Bayer AG, 2007, and 3.3 mg/m³, report 16070, Bayer AG, 1987, respectively).
According to TRGS 430 there is even an option to set the EBW > 10 * AGW. This was done for HDI oligomers, iminooxadiazindione type and also for its read-across substance HDI oligomers, isocyanurate type taking into account that there were data from the read-across substance on pulmonary irritation as well as on repeated (e.g. subchronic) inhalation exposure available, which clearly show that the respiratory damage is linked to the inhaled irritating concentration, and does not exacerbate during repeated exposure (Pauluhn, Inhal. Toxicol., 13, 2001, 513-532 and 14, 2002, 287-301).
Therefore the EBW = DNELlong-term local effects for inhalation is set 0.5 mg/m³.
This is in line with a published proposed TLV-TWA of 0.5 mg/m³ (Pauluhn and Mohr, Inhal. Toxicol., 13, 2001, 513-532). The value is further in the same order of magnitude compared to a DNEL delineated according to Guidance Document R.8 (ECHA, Nov. 2012).
AGWs are based on 8-hour time weighted average exposure. According to the German rule for OELs (Technical Rule for Hazardous Substances 900, BMAS, 2006/2013) an exposure limit for short-term ceiling concentrations could be established by multiplication to an exceeding factor (Überschreitungsfaktor), which is set per default 1 (could be adjusted to max. 8) . Pauluhn and Mohr proposed a maximum concentration limit of 1.0 mg/m³ (exceeding factor 2) for HDI-derived polyisocyanates. This value was used as surrogate DNELacute, local effects for inhalation for HDI oligomers, iminooxadiazindione type. This procedure is in accordance to Guidance Document R.8 (ECHA, Nov. 2012), Appendix R. 8 -8, Box 6.
For skin sensitization no DNEL is calculated as the relationsship between skin dose and response is not clear. Furthermore, there is no validated method of DNEL calculation for skin sensitizers, therefore a quantitative risk assessment for this endpoint is not possible and a qualitative risk assessment is applied. As the substance is classified with R43/Cat. 1 for skin sensitisation (without sub-categorisation), it has to be allocated to the high hazard category (Guidance Document - Part E: Risk characterization, ECHA, Nov. 2012). Consequently, the respective risk management measures (RMMs) at the workplaces have to be considered for risk assessment.
The DNEL acute/long-term for inhalation for workers covers also reproductive toxicity, as the local effects at the respiratory tract are the most sensitive effects.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again