Silicon carbide

Endpoint summary

Additional information

Silicon carbide particles (SCP) can be set into the category of particles which have a very low solubility (poorly soluble particles, PSP) (see chapter 4.8.). The toxicity testing of this kind of material is based on its possible harmfulness on the respiratory tract. The relevant pathological mechanisms are associated with the primary interaction of the particles with alveolar macrophages (AM) and the ensuing (following) cascade of inflammatory processes.

In vitro toxicity test with AM are thought to mimic the decisive response to the particles exposure. The vector model (VM) uses four different parameters to document the dust effects on the AM, the pathological stimulation with the secretion of potent bioactive substances (ROS) and TNF alpha and the damage of the cell function (Glucuronidase, forced ROS liberation by PMA). The VM is closely linked to thein vivotoxicity by the application of the samples via intratracheal instillation (ITI). Dose calculationin vitroandin vivois established to the same number of AM per mass unit applied substance(Rehn et al., 1992; Rehn and Rehn, 1999; Bruch et al., 2004).

Overload is the most critical situation in testing particles; this applies for both the in vitro and in vivo experiment. According to Morrow overload characterizes a volumetric limit for upload of particles by AM(Morrow, 1991). Overload evokes additional effect mechanisms not related to particle characteristics and which are not relevant for the human risk extrapolation. In the standard rat model the exposure via ITI or inhalation 3 mg test sample/g rat lung denotes this critical condition(Elder et al., 2005; Valberg et al., 2009).

The assessment by the Silicon Carbide Manufacturer Association (SiCMa) is based upon literature review and upon the results of specific testing conducted in several laboratories includingofEmission-evaluation (IBE). IBE toxicological testing is strictly restricted to the suboverload range: the highest dose is 120 µg/10⁶AM in the in vitro VM corresponding to 4.8 mg/rat lung (BW, female, Wistar). Typically the IBE uses a multi dose model by cutting half this upper dose (fig 1): e.g. 120; 60; 30 ... in the VM resp. 4.8; 2.4; 1.2; .... in the rat lung.

The IBE scheme of risk estimation in the biological test system is based on the bench mark dose (BMD). In using the low level multi-dose regime exposure levels with no adverse effect levels (NOAEL) and lowest adverse effects levels (LOAEL) should be identified. In Figure 1 the highest no effect level is used as the toxicological bench mark.

All NOAELs of the sample are referenced to the positive control resp. to the negative control (quartz DQ12 and corundum). The NOAEL of a particular test sample can then be assigned to a distinct rank of the BMD. E.g. rank O is similar to corundum and the sequential cutting half steps assign the toxicity rank I, II, III, IV, V.

This assessment system shows that silicon carbide particles can be classified as poorly soluble particles with very low toxicity comparable to corundum (alumina) and titanium dioxide (see Figure 1 in Assessment Reports - Analogy to titania and alumina).

The mutagenicity of Sic was first approached through the Ames test.The bacterial reverse mutation assay (Ames test) clearly showed SiC to be non mutagenic (Bioservice, 2008; OECD 471). According to REACH, additional mutagenicity information is required.

As demonstrated before, silicon carbide (SiC)*is a member of the family of “poorly soluble particles of low toxicity”. Two other members of this family for which extensive mutagenicity data are available are Alumina [Al₂O₃] and Titania [TiO₂]. These data were recently reviewed by scientific experts who came to the following conclusions:

• “The results of most in-vitro genotoxicity studies with Titanium dioxide were negative” (IARC, 2006);
• “Aluminium compounds have produced negative results in most short-term mutagenic assays” (Krewski et al, 2007).

 

SiCMa is of the opinion that the above two conclusions, which are quite similar, would also apply to silicon carbide and that conducting additional testing, not only is not in the spirit of REACH, but would add very little to the above body of knowledge.

Reviewing numerous data carries more weight than conducting additional tests. This is especially true in the field of poorly soluble particles because of no definite agreement in the scientific community on the most relevant test and on the interpretation of test results (Schins et al, 2007). The variety of protocols used so far for testing of poorly soluble particles has probably induced a degree of variation in the test results. But studies revealed the importance of particles’ size. Dust particles (so called “fine” particles), such as SiC dust, are too large to reach the genome*.

In-vitro studies with the vector model confirmed a low intrinsic inflammatory potential of SiC particles (Bruch et al, in press). Long-term intratracheal studies in rats (Bruch et al, 1993) and sheep (Bégin et al, 1989) exposed to SiC particles did not reveal persistent inflammation and a 30 months intraperitoneal test with rats did not show an increased incidence of tumours (Roller et al, 1996).

All the information summarized above supports the view that:

• SiC is belonging to the group of poorly soluble particles of low toxicity, such as Alumina (corundum) and Titania (TiO2);
• The vector model assessment system is ranking SiC in the same range of very low toxicity as Alumina and Titania (see Fig 1);  
  • As the three compounds have quite similar physico-chemical and toxicological characteristics, it is justified to use the “read across” approach to assess mutagenicity of SiC;
  • The magnitude of evidence does not support a relevant mutagenic potential for Alumina and Titania;
  • SiC is similar to Alumina and Titania in that regard;
  • Therefore, performing additional mutagenicity testing for SiC is not considered reasonable.

*SiC nano particles and fibres (i.e. whiskers) are not in the scope of this registration dossier

 

The full literature references can be found in 13 Assessment Reports- Analogy to titania and alumina

 

 

Short description of key information:

The mutagenicity of Sic was first approached through the Ames test. The bacterial reverse mutation assay (Ames test) clearly showed SiC to be non mutagenic. According to REACH, additional mutagenicity information is required.

Silicon carbide (crude and grains) is a member of the family of “poorly soluble particles of low toxicity”. Two other members of this family for which extensive mutagenicity data are available are Alumina [Al2O3] and Titania [TiO2]. These data were recently reviewed by scientific experts who came to the following conclusions:

“The results of most in-vitro genotoxicity studies with Titanium dioxide were negative”;

“Aluminium compounds have produced negative results in most short-term mutagenic assays”.

SiCMa is of the opinion that the above two conclusions, which are quite similar, would also apply to silicon carbide and that conducting additional testing, not only is not in the spirit of REACH, but would add very little to the above body of knowledge.

Endpoint Conclusion: No adverse effect observed (negative)