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Key value for chemical safety assessment

Additional information

Data on Category UCVB streams

In vitro

The mutagenic potential of the streams Pyrolysis C5s (CAS No 68476 -55 -1) and Hydrotreated C5s (CAS No 68602 -79 -9) has been assessed in 4 strains of Salmonella typhimurium (TA1535, TA1537, TA98, and TA100) and in a tryptophan dependent mutant of Escherichia coli, strain WP2uvrA/pKM101 (HLS, 2004 c & d). No evidence of mutagenic activity was seen at any concentration of Pyrolysis C5 or Hydrotreated C5s in either test. In conclusion, under the test conditions employed, Pyrolysis C5s and Hydrotreated C5s showed no evidence of mutagenic activity in either bacterial system.

The mutagenic potential of 1,3 -pentadiene (piperylene) has been assessed in Salmonella typhimurium (5 or 6 strains with and without metabolic activation) with no evidence of mutagenicity (EBSI, 1991b & 1992b).

In vivo

Pyrolysis C5s (CAS No 68476 -55 -1) and Hydrotreated C5s (CAS No 68602 -79 -9) have been evaluated for their ability to induce micronuclei in bone marrow cells of CD-1 male mice (HLS, 2004 e & f). No statistically significant increase in the incidence of micronucleated PCE were observed in the Pyrolysis C5 exposed animals compared with the negative control values. For Hydrotreated C5s, no statistically significant increases in the frequency of micronucleated immature erythrocytes were observed in mice following two 6-hour whole body inhalation exposures at 2,000; 4,000; and 8,000 ppm compared with control values (P>0.01 in each case). A small but statistically significant decrease in the proportion of immature erythrocytes was observed in animals exposed to Hydrotreated C5s.The proportion of immature erythrocytes was within the normal range of variability for this species and was therefore not considered to be of any biological importance. In conclusion, neither Pyrolysis C5s nor Hydrotreated C5s showed any evidence of causing chromosome damage or bone marrow cell toxicity when administered by whole body inhalation to CD-1 male mice.

Data on specific components

1,3 -pentadiene has been evaluated for its ability to induce micronuclei in bone marrow cells of male and female B6C3F1 mice and CrlCDBR rats (EBSI, 1992 c & d). For mice the target inhalation concentrations were 30, 100 and 300 ppm equivalent to 83, 278 and 834 mg/m3. 1,3 -pentadiene did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered by whole body inhalation to CD-1 male mice and CrlCDBR rats.

Some components within the category UVCB streams are classified for mutagenicity under DSD (isoprene, benzene,1,3 -butadiene and 2 -methylbut-2-ene).

Isoprene (Classification: DSD – Harmful Xn Mutagen Cat 3 R68; CLP - Category 2, H341): Isoprene has been examined for mutagenicity both in vitro and in vivo in a range of recognised core assay types. 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. Isoprene is considered to be genotoxic in vivo, having shown clear effects in the mouse (Tice et al, 1988; Placke et al, 1996; NTP, 1999).

Benzene (Classification: DSD –Toxic T Mutagen Cat 2 R46; 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. Benzene has been shown to be mutagenic in vivo in both somatic cells and germ cells (Ciranni et al, 1991). Data is also available for human exposure (Albertini et al, 2001, 2003 & 2007)

1,3-Butadiene (Classification: DSD –Toxic T Mutagen Cat 2 R46; CLP - Category 1B, H340): There are many studies on human in occupational settings. The available data on several groups of 1,3-butadiene-exposed workers, both in 1,3-butadiene monomer production and in the polymerization of 1,3-butadiene, did not show any association between 1,3-butadiene exposure and increased gene mutations, primarily HPRT mutations (Albertini et al, 2001, 2003 & 2007, Wickliffe et al 2009). One group of investigators have shown a relationship in workers exposed to 1,3-butadiene but a different method was used by these investigators to measure the HPRT mutation than in the other studies, and there are questions on whether co-exposures were adequately accounted for. Nevertheless, a recent study from these investigators has shown that reduced exposures to all potential genotoxic agents in these facilities have resulted in negative findings (Wickliffe et al, 2009). No 1,3-butadiene-related chromosome aberrations have been demonstrated in humans (Albertini et al 2001, 2003, 2007).

2-methylbut-2-ene (Classification: DSD – self classified Cat 3 R68; CLP - Category 2, H341) 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 but positive results in a number of studies in vivo in the bone marrow micronucleus assay (EBSI, 1991b & c; BASF, 2009). It is concluded that the available data indicate that 2-methylbut-2-ene is genotoxic in vivo.

 


Short description of key information:
Although data on C5 non-cyclic streams indicate that they are not genotoxic, the marker substance in this category, isoprene, is genotoxic. Therefore all the C5 non-cyclics are considered to warrant classification under DPD and CLP for genotoxicity.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

CAS number 68477-35-0 is listed in Annex VI of CLP and is classified as follows Mutagenic Cat 2, R46 according to Dir 1999/45/EC and Cat 1B, H340 under CLP Reg (EC) 1272/2008.

All other UVCB streams in this category warrant classification for mutagenicity on the basis that they all contain >=1% isoprene. Classification as Mutagenic Category 3, R68 under DPD with the corresponding classification as a germ cell mutagen Category 2 H341 (Suspected of causing genetic defects) under CLP applies.

For streams which contain >=0.1% 1,3 -butadiene or benzene, classification should be Mutagenic Cat 2, R46 under DPD and Cat 1B, H340 under CLP.