Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In vitro and in vivo genotoxicity data are available for two specific streams identified for this category:

CAS 68477-54-3 (Low Dicyclopentadiene Resin Oil): No positive mutagenic response was observed in a bacterial reverse mutation test using Salmonella typhimurium tester strains TA98, TA100, TA1535 and TA1537 and Escherichia coli tester strain WP2 uvrA in the presence and absence or Aroclor-induced rat liver S9 (BioReliance, 2004a). Negative results were also seen in vivo. Not statistically significant increase in micronucleated polychromatic erythrocytes was seen in male or female mouse bone marrow when evaluated after two administrations, approximately 24 hours apart. The highest dose administrated on the study was 1750 mg/kg (DuPont, 2004c).

CAS 68478-10-4 (Dicyclopentadiene/Codimer Concentrate): This stream was shown to have no mutagenic activity in a bacterial reverse mutation test using Salmonella typhimurium tester strains TA98, TA100, TA1535 and TA1537 and Escherichia coli tester strain WP2 uvrA in the presence and absence or Aroclor-induced rat liver S9 (BioReliance, 2004b). No evidence of genotoxicity was seen in an in vivo mouse micronucleus test dosed at 1750 mg/kg (2 doses at 24 hour interval) (DuPont, 2004d).

Specific components which have been identified as present in some streams and shown to be mutagenic in vivo are benzene, 1,3-butadiene and isoprene:

Benzene (Classification: EU –Toxic T Mutagen Cat 2 R46; GHS/CLP - Category 1B, H340): Benzene has been extensively examined for mutagenicity both in vitro and in vivo in a range of recognised core assay types. It has shown mixed results for mutagenicity in vitro although in mammalian cells there is overall evidence for potential mutagenic activity (EU, 2008b). Benzene has been shown to be mutagenic in vivo in both somatic cells and germ cells (Ciranni et al, 1991).

1,3-Butadiene (Classification: EU –Toxic T Mutagen Cat 2 R46; GHS/CLP - Category 1B, H340): In non-human studies, 1,3-buta-diene is genotoxic in vitro and is genotoxic in vivo in both somatic and germ cells in the mouse (Araki et al, 1994; Asakura et al, 2008; Adler et al, 1994). The available data on several groups of 1,3-butadiene-exposed workers did not show any association between 1,3-butadiene exposure and increased gene mutations, primarily HPRT mutations. No 1,3-butadiene-related chromosome aberrations have been demonstrated in humans (Albertini et al, 2001; 2003; 2007).

Isoprene (Classification: EU – Harmful Xn Mutagen Cat 3 R68; GHS/CLP - Category 2, H341): Isoprene has been examined for mutagenicity both in vitro and in vivo in a range of recognised core assay types. It has shown negative results for mutagenicity in vitro in the core endpoints of bacterial mutation and cytogenetic damage, both with and without S9. However, isoprene induced DNA damage (strand breaks) at high concentrations in a mammalian cell line in vitro. These effects were only observed in the presence of S9. There are several reports of isoprene inducing micronuclei in the bone marrow of mice exposed for different times from 12 days through to 80 weeks. A single examination in the rat reported a negative result for micronucleus induction, although this was in lung fibroblasts and not in bone marrow cells. A direct comment on the relative sensitivity to genotoxic effects of isoprene in the mouse and rat is therefore not possible. Isoprene is considered to be genotoxic in vivo, having shown clear effects in the mouse (HLS, 2003; NTP, 1995).

References

EU (2008b). European Union Risk Assessment Report for Benzene. EC Joint Research Centre. http: //ecb. jrc. ec. europa. eu/documents/Existing-chemicals/RISK_ASSESSMENT/REPORT/benzenereport063. pdf.


Short description of key information:
In vitro and in vivo genotoxicity data are available for 2 streams within this category - CAS 68477-54-3 (Low Dicyclopentadiene Resin Oil) and CAS 68478-10-4 (Dicyclopentadiene/Codimer Concentrate). These studies show negative results. However, there are substantial data on the genotoxicity of a number of specific components present in some streams. Of these, benzene, 1,3-butadiene and isoprene have been shown to be mutagenic in vivo. Streams that contain ≥ 0.1% benzene or 1,3-butadiene or ≥ 1% isoprene are considered to be mutagenic and will require classification for this end-point.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

Available data for streams in this category and specific components present within some streams indicate the Resin Oils and Cyclic Dienes that contain <0.1% benzene and <0.1% 1,3-butadiene and <1% isoprene are considered not to be mutagenic and no classification will be required under Dir 1999/45/EC or Reg (EC) 1272/2008.

It is proposed that Resin Oils and Cyclic Dienes streams containing ≥0.1% benzene or ≥0.1% 1,3-butadiene are classified as Mutagenic Cat 2, R46 under Dir 1999/45/EC “May cause heritable genetic defects” or Cat 1B, H340 under Reg (EC) 1272/2008 “May cause genetic defects”.

Resin Oils and Cyclic Dienes streams that contain <0.1% benzene and <0.1% 1,3-butadiene but contain ≥1% isoprene are considered to be possible mutagens and are classified as follows: Mutagenic Cat 3, R68 under Dir 1999/45/EC “Possible risk of irreversible effects” and Cat 2, H341 under Reg (EC) 1272/2008 “Suspected of causing genetic defects”.