Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

The genotoxicity data on streams within this category include in vitro bacterial reverse mutation and in vivo mouse bone marrow micronucleus assays on one low naphtha stream (CAS 68476-55-1). These studies showed no evidence of mutagenicity or clastogenicity. Three genotoxicity studies on a related stream (CAS 64741-68?0) were less conclusive . Two in vitro gene mutation assays in Mouse L5178Y cells gave equivocal results, while an in vivo mammalian bone marrow chromosome aberration test in ratsCAS 64741-68?0did not induce chromosomal aberrations and gave a negative result.

In vitro data

CAS 68476-55-1 was tested in a bacterial reverse mutation test using Salmonella typhimurium tester strains TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A pKM 101 in the presence and absence of metabolic activation. Concentrations of the test substance up to 0.525% v/v (5250 ppm; 50% of the Lower Explosive Limit) were tested in the mutation tests in vapour phase. CAS 68476 -55 -1 showed no evidence of mutagenic activity in this bacterial system.

In a L5178Y TK+/- mouse lymphoma mutagenesis assay CAS 64741-68-0 heavy catalytic reformed naphtha API 83-06 was soluble at all concentrations tested. Without activation, API 83-06 was tested from 6.25-75 nL/mL and a wide range of toxicities was induced without inducing significant increases above the background mutation frequency. With metabolic activation, API 83-06 at 6.25-120 nL/mL induced small but repeatable increases in the mutant frequency that ranged from 1.8-fold to 2.2-fold above the background mutant frequency.

In a second L5178Y TK+/- mouse lymphoma mutagenesis assay with CAS 64741-68-0 three non-activated cultures that were cloned exhibited mutant frequencies which were significantly greater than the mean mutant frequency of the solvent controls (mutant frequencies 31.0, 3.6 and 2.0 times greater than controls and respective total growth was 1, 2 and 10%). The lower limit for considering data in this assay is generally 10% survival, and hence this is a weak increase at the limit of toxicity. As the test material had a very steep toxic response curve in this system, minute differences in dose resulted in large differences in total growth. The total growth exhibited by each culture may be more representative of dose delivered than the concentration of API 83-06 indicated. A comparison of induced mutant frequency with total growth indicated a dose-dependent response. It was concluded that CAS 64741-68-0 produced an equivocal response in the presence and absence of exogenous metabolic activation.

In vivo

CAS 68476-55-1 was evaluated in a mouse micronucleus test chromosome aberration assay. Groups of 7 male CD-1 mice were exposed for two 6-hour whole body exposure periods, on consecutive days, at target concentrations of 40, 150 and 500 ppm. All animals were sacrificed approximately 24 hours after the second exposure period. No statistically significant increase in the incidence of micronucleated PCE were observed in the animals exposed to CAS 68476-55-1 compared with the negative control values. The results demonstrated that Pyrolysis C5s was not clastogenic toward mammalian cells in vivo.

Activity of CAS 64741-68-0 was assessed in an acute in vivo cytogenetics assay OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test). Male and female Sprague Dawley rats were given 300, 1000 or 3000 mg/kg as a single ip injection. Bone marrow cells, arrested in metaphase and collected 6, 24 and 48 hours after treatment, were examined microscopically for numerical and structural chromosome aberrations.  The results of the assay indicated that CAS 64741-68-0 did not induce chromosomal aberrations in bone marrow cells of male or female rats.


Short description of key information:
One low benzene naphtha stream has been examined for genotoxicity and has shown negative results both in vitro and in vivo. Toluene has been examined for genotoxicity both in vitro and in vivo in a range of assays and again has shown negative results. A related stream 64741-68-0 heavy catalytic reformed naphtha gave equivocal or weakly positive results in two in vitro L5178Y assays for mutagenicity but was not genotoxic when tested in vivo in a mouse bone marrow micronucleus assay. As this stream is not included in this category and as the in vivo data is considered to be more relevant than equivocal in vitro data it is concluded that the available data are sufficient and indicate that low benzene naphtha streams have no significant genotoxicity.

Endpoint Conclusion:

Justification for classification or non-classification

It is concluded that the available data on low benzene naphtha streams and on the specific component toluene are sufficient for assessment and that no classification under Dir 67/548/EEC or GHS is warranted.