④ Monitoring international activities
Implemented by the National Institute of Advanced Industrial Science and Technology, and Keio University
Final goal: To keep our project members informed with standardization activities of international organizations such as the OECD WPMN (Working Party on Manufactured Nanomaterials) and the ISO TC229 (Nanotechnologies) and with regulatory actions taken by the United States, the European Union and others, and to contribute our project results to the above international standardization activities timely and effectively.
Main results:
Contribution of our project results to OECD activities
(1) Contribution to amending OECD Test Guidelines (TGs) on inhalation toxicity
Since May 2013, our project members had participated in drafting an SPSF (a working proposal) for amending inhalation TGs led by the US EPA under the OECD WPMN to contribute to the discussions on, among others, making bronchoalveolar lavage (BAL) analyses mandatory. The SPSF was submitted by the WPMN to the WNT (Working Group of the National Coordinators for the Test Guidelines Program) in November 2013, and adopted at the 26th meeting of the WNT in April 2014.
Our project members participate in the expert group on inhalation TG amendments for nanomaterials, established in the WNT in May 2015 and chaired by the US EPA. The expert group firstly focuses on drafting amended TG 412 (Subacute Inhalation Toxicity: 28-Day Study) and TG 413 (Subchronic Inhalation Toxicity: 90-Day Study) together with studying the feasibility of inclusion of lung burden measurement. The expert group will then start drafting Guidance Document (GD) 39 on Acute Inhalation Toxicity Testing, to which inclusion of a discussion on instillation and insufflation studies is proposed.
[External Link: download site for OECD-TGs of Section 4: Health Effects]
[External Link: download site for OECD-GDs]]
(2) Presentations of our project results at WPMN Expert Meetings
Under the WPMN SGTA (Steering Group on Testing and Assessment), a series of horizontal workshops (Expert Meetings) have been held to examine applicability of OECD-TGs — which were developed for general chemicals — to nanomaterials, based on the experience gained through the Sponsorship Program for Safety Testing of Representative Manufactured Nanomaterials. A project member presented our project results at the Expert Meeting on Toxicokinetics of Nanomaterials held in Seoul, Korea in February 2014 and the Expert Meeting on Categorization of Nanomaterials held in Washington DC, US in September 2014:
– Masashi GAMO “Intratracheal Administration Study for Initial Characterization of Toxicokinetics of Nanomaterials”; and
– Masashi GAMO “Development of Equivalence Criteria for Nanomaterials by Intratracheal Administration Study”.
Reports on both Experts Meetings are expected to be published in 2016.
Furthermore, a project member presented results of the preceding project with the following title at the Expert Meeting on Inhalation Toxicity Testing for Nanomaterials held in The Hague, the Netherlands in October 2011, the early days of the present project, where he stated that “The combination of inhalation and instillation is effective in dealing with the diversity of nanomaterials with limited budget and time.”: Takuya IGARASHI “Japan’s approach to inhalation toxicity testing of CNTs in the NEDO Project (P06041)”. The report of this Expert Meeting was published in June 2012 under the OECD Series on the Safety of Manufactured Nanomaterials. [External Link: reportPDF 498 KB]
In addition, at the WPMN meeting in February 2015, holding an information sharing seminar on in vivo inhalation toxicity screening methods was proposed by project members and then approved. The seminar will present state-of-art research results on intratracheal administration testing, as well as short-term inhalation testing developed by BASF and others, and is hosted by the US EPA together with a meeting of the expert group on inhalation TG amendments for nanomaterials mentioned in 1) above that is held in Washington DC, USA on September 21 – 22, 2015.
Fig.④ At a break during a WPMN meeting in the OECD HQs, Paris in 2014
(3) Leading a survey on use and development of concepts of grouping, equivalence and read-across
Under the WPMN SGAP (Steering Group on Risk Assessment and Regulatory Programs), a project member proposed conducting a “survey on approaches to develop or use concepts of grouping, equivalence and read-across based on physical-chemical properties of nanomaterials for their human health and ecosystem hazard assessment in regulatory regimes” and plays the role of the project leader. The questionnaire survey for OECD WPMN members was conducted in October- December 2013. He made a keynote lecture on the outline of the survey results at the above mentioned Expert Meeting on Categorization of Nanomaterials in 2014.
The report of the survey is still in the state of a draft, which will be submitted to the WPMN meeting in November 2015, and expected to be published in 2016. This survey provides good opportunities to show our research results since it took equivalence as a key concept as grouping and read-across while OECD-GD 194 on Grouping of Chemicals does not show the concept of equivalence. [External Link: OECD-GD on Grouping of Chemicals PDF 1853 KB]
(4) Under the WPMN’s Sponsorship Program for Safety Testing of Manufactured Nanomaterials, our project’s toxicokinetic data on intravenously administered titanium dioxide nanoparticles in rats was, at Germany’s request, contributed to dossiers on titanium dioxide co-sponsored by Germany and France, at the end of March 2013. The dossiers on titanium dioxide were published on July xx, 2015 with a delay from dossiers on other eight nanomaterials published from the OECD’s website on June 9. [External Link: OECDdownload site for OECD dossiers]
Contribution of our project results to ISO TC229 activities
(5) Under the TC229 WG3 (Health, Safety and Environmental Aspects of Nanotechnologies), a project member participates in developing Technical Report ISO/TR 18637 “General framework for the development of occupational exposure limits (OEL) and bands (OEB) for nano-objects and their aggregates and agglomerates” led by the US NIOSH, where he has succeeded in reflecting so much of Japan’s research results on inhalation risk assessment including a thought on equivalence criteria. This Technical Report is expected to be published in 2016.
[External Link: standards and projects under the ISO TC 229]