Notification of Inorganic Compound under China REACH

1. Background

China adopted new chemical substance notification approach in 2003. It follows the principle of “prevention” and pay close attention on the unknown risks posed by new chemicals so as to have an effective management of them.

Human being’s ever-growing demand for new materials, products with special function have served as a propeller for the development and research of new chemical substances. However, new chemical substances of special properties usually present unpredictable risks to human beings and the global environment, of which little is known. Inorganic substances fall under this category. Based on the statistics published by MEP, by the end of Dec, 2013, over 90% new substances notified through simplified notification are organic substances, only less than 5% are inorganic substances. Furthermore, less than 2% substances notified through regular notification are inorganic substances (up to 2013/12/17, only 2 substances are inorganic in the 120 new chemical substances published on MEP website). Due to intrinsic difficulties inherent in notification of inorganic substances and the lack of real case experiences and guidance documents(such as particular testing data requirements), notification of inorganic substances turns out to be a thorny field for industries concerned.

2. Challenges

The potential difficulties in the notification of inorganic compounds can be summarized in the following two major aspects.

2.1 Experimentation

Tests involved in the process of new chemical substance notification (China NCSN) mainly include substance identification, physicochemical, toxicological and eco-toxicological testing.

As for organic substances, it is quite straightforward to assign testing labs to finish the tests required and generate report based on the testing results. However, as for inorganic substances, it is quite a different scenario. The major technical problem is the quantitative analysis: whether it can be processed successfully or not will have fundamental impact on the subsequent testing arrangement.

The following table summarizes the testing items/endpoints which would be influenced in general case of simplified notification and regular notification.

Table. Endpoints that require quantitative analysis

The quantitative analysis is the foundation of many testing items, lack of a proper analysis method will lead to difficulty in generating the dose-toxicity relationship, which, ultimately will render the testing results meaningless. For a common organic compound, there are quite a few applicable quantitative methods to choose among, such as HPLC, GC, GC-MS, TOC and the same is true for qualitative methods such as NMR, UV-VIS, MS. However, these methods will all be invalid for inorganic chemicals, since there does not exist a single carbon atom in the structure of inorganic chemicals while the analysis methods such as NMR, MS and TOC are developed and constructed based on the calibration of carbon atoms. Even worse, chromatograph will be powerless, since the separating efficiency is too low to ensure a credible result. The inorganic compound showed no absorption band in the UV-VIS region, for a large proportion of the domestic PC and eco-toxicological laboratories, the detector of their analysis apparatus is UV-VIS based, thus the HPLC and GC will not work either.

The notification of inorganic compounds seems insolvable. However, there are still some unconventional methods worth a trial, which are explained as follows:

1. If the inorganic substance is ionic compound, we should look deep into its structure and study the characteristics of both the anion and cation. If either of the anion or the cation can react with a certain regent and show clear reaction endpoint, the titration method could be adopted;

2. If the molecular of inorganic substance contains metal atoms such as Na, K, B, V, Fe, Cr, the ICP-AES may be the accredited apparatus to undertake the testing, with the accurate concentration of the metal element be calculated through the standard curve;

For some inorganic compounds, the ICP and titration may not be applicable. Since some inorganic substances can react with certain organic compound and develop a reaction complex which could show an observable absorption of UV-VIS region. In this way, the derivant of the inorganic compound could be subject to analysis and calculation, while the concentration of the inorganic compound could be obtained through extrapolation.

To ensure a scientific, reliable and relevant result, the specific method should not only be determined by the intrinsic structure and properties of the compound, the testing conditions should also be taken into account. Below is a real case study to be shared.

Case Study: The lab experienced difficulties in the development of analysis method for the inorganic substance “sodium pentaborate”.

Although it appeared more than one recommended approaches as listed above could be adopted: the ICP could be used to quantify the sodium; the titration method could be applied to quantify the boron (B), the real situation turned out otherwise. After full consideration, it was realized that the above methods would not be workable, since the test solution was nutrient medium containing various salts, like H₃BO₃, Na₂MoO₄, Na₂EDTA, NaHCO₃ and so on, and the existence of same elements or irons would greatly impact the testing result. Literature and national standard like ASTM D 3082-2009 were studied and an alternative was found in the end.

The analysis method for Boron in water is as follows: curcumin isopropanol solution could react with soluble boron in water in the acid condition and in the presence of oxalic acid, and then a red-colored complex called rosocyanine is formed when the treated solution is evaporated to dryness in water bath. Then the complex is dissolved by isopropyl and is read spectrophotometrically at 540nm using a 4cm cuvette. Finally the standard curve and the linear range were obtained and the concentration of the sodium pentaborate was calculated through extrapolation.

2.2 Quantitative Risk Assessment

It is worth mentioning that another factor, which contributes to the enhanced complexity of inorganic substance notification, is the necessity to compile the quantitative risk assessment. As stipulated in the provision, a quantitative risk assessment is required for tier 2/3/4 of regular notification. However, lack of some important endpoints such as Log Kow (Partition coefficient of n-octanol/water) will definitely lead to the difficulty in assessing the absorption/desorption process. Further, due to the inherent structure and characteristics of the inorganic substances, most of the estimation software cannot generate a scientifically reliable estimated result, thus the exposure assessment will be difficult to perform.

Without any officially released guidelines and well-recognized workable approaches, the notifiers usually find them in a dilemma in cases of such problems.

Under such scenario, some CSR reports of metal inorganic compound under EU REACH could be referred. Some default setting could be adopted for the paramters of the exposure model (see below), which could simplify the quantitative assessment to some extent.

• Kd (Partition coefficient in different agents) is used instead of Kow;

• The degradation rate is 0;

• For parameter of the STP (sewage treatment plant), when there is no measured value available, the default removal rate for metal cation is 50%;

• Absorption/desorption: measured values in different agents are used as reference;

3. Summary

However, it should be realized that there are not any specific documents/guidance either in China and EU. Tentative research and study are still being carried on. It could be predicted that there might exist a lot of details to be explored and discussed. Meanwhile, it is believed that the government is fully aware of the difficulties experienced by the industries, even though practical steps have yet been landing on the ground.