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EC number: 265-078-2
CAS number: 64741-77-1
A complex combination of hydrocarbons from distillation of the products from a hydrocracking process. It consists predominantly of saturated hydrocarbons having carbon numbers predominantly in the range of C10 through C18, and boiling in the range of approximately 160°C to 320°C (320°F to 608°F).
In Vitro Genetic Toxicity
In vitro gene mutation in bacteria
A total of 13 in-vitro gene mutation assays have been identified. In a
series of studies (May 2013) nine substances from the VHGO category were
tested in a modified Ames assay. Mutagenic activity of complex aromatic
hydrocarbon mixtures such as mineral oils was inadequately detected by
the standard Ames assay. Consequently, modification of the assay was
needed. An optimised assay was developed, in which a DMSO extract of the
oil instead of the whole oil was tested. DMSO is able to extract the
principle carcinogenic components (polycyclic aromatic hydrocarbons)
from oils, and allows them to be tested without other ingredients
interfering with the mutagenic response. As some components of oils were
found to inhibit PAC metabolism, the metabolic activation system was
modified by increasing the S9 concentration 8-fold and doubling of the
NADP co-factor concentration. Hamster S9 instead of rat S9 is used in
this assay and only the most sensitive strain of bacteria for PACs
(TA98) is used. The test, referred to as the Modified or Optimised Ames
Assay, is recognised as an ASTM method (E1687-95) and substances with an
Mutagenic index (MI) greater than 1 are considered to be mutagenic. In
these nine studies eight of the materials tested showed no evidence of
mutagenic activity (MI values between 0.2 and 0.7). One sample gave an
ambiguous, weak response (MI 1.07). Additional bacterial studies proved
either negative for gave weak/ambiguous results. In-vitro SCE and mouse
lymphoma studies gave equivocal results.
A work program is underway to provide additional evidence and
justification for the use of the optimised Ames assay instead of the
standard test for petroleum substances.
In vitro gene mutation in mammalian cells
A sample of diesel fuel was found to be negative in the mouse lymphoma
assay for forward mutation at the thymidine kinase (TK) locus
(Jagannath, 1978). The test was carried out both in the presence and
absence of mouse liver microsome fraction and dose ranged between 0.064
and 0.5 ul/ml.
In vitro cytogenicity in mammalian cells
In a read-across in vitro cytogenicity study (API, 1988)
hydrodesulfurised middle distillate was tested at dose levels of 0.008,
0.016, 0.03 and 0.06 µL/mL in the absence of S-9 and at dose levels of
0.13, 0.25, 0.5, and 1µL/mL in the presence of S-9 activation.
Hydrodesulfurised middle distillate did not induce an increase in SCEs
in the CHO cells in the absence of S-9 activation. In contrast, there
was a statistically significant increase in the frequency of SCEs at two
consecutive low dose levels when compared to the solvent control in the
presence of metabolic activation. However, an inverse dose-response
trend was observed with no significance at the highest two doses tested.
The positive control induced SCEs as expected.
Based on these results, the study authors concluded that
Hydrodesulfurised middle distillate did not induce an increase in SCEs
in CHO cells in the absence of S-9. However, due to a statistically
significant increase in SCE frequency at two consecutive low dose
levels, the study authors concluded that Hydrodesulfurised middle
distillate was equivocal for induction of SCEs in the CHO cells in the
presence of S-9.
In Vivo Genetic Toxicity
Additional testing is planned for four substances in the VHGO category;
combined in vivo Comet assay and micronucles tests are proposed. These
will help to fill data gaps and confirm conclusions on genetic toxicity.
In a micronucleus assay (McKee et al., 1994), fifteen male and female
CD-1 mice were treated with 1.0, 2.5, or 5.0 g/kg of home heating oil
dissolved in corn oil via oral gavage. A concurrent control group
received only corn oil, while another group served as positive control
and was treated with 0.04 g/kg cyclophosphamide. There was no increase
in the frequency of micronuclei for the test material. In addition,
there was no evidence of bone marrow depression. Cyclophosphamide, the
positive control, exhibited appropriate results and the vehicle control
result was within the normal range. Based on these results the study
authors concluded home heating oil did not exhibit a positive response.
Additional supporting data is available from in vivo genotoxicity
studies conducted in rats. Diesel fuel was observed to be clastogenic in
a chromosome aberration test (Jagannath, 1978) when tested
intraperitoneally in rats at dose of 0.6, 2.0, and 6.0 mL/kg.
Diesel fuel no. 2 was investigated in a mouse dominant lethal assay
(API, 1980cc). Male mice were exposed by inhalation to diesel fuel at
airborne concentrations of 100 and 400 ppm, 6 hours per day, 5 days each
week for 8 weeks (40 exposures). The results showed that the test
material did not cause significant increases in either pre- or
post-implantation loss of embryos compared to negative controls. The
sensitivity of the assay was confirmed by a significant increase in
dominant lethal mutations in the females that had been mated with the
males treated with the positive control substance. It was concluded that
diesel fuel did not cause dominant lethal mutations at 100 or 400 ppm.
Key and supporting data (including read-across) are available from a
number of studies that have examined the mutagenicity and genotoxicity
of VGOs/HGOs/Distillate fuels in vitro and in vivo.
From the results observed and the difficulties known to arise with the
testing of complex hydrocarbon mixtures in the Ames assay, it can be
concluded that the standard Ames test and the yeast cell mutation assay
are unlikely to give reliable findings. The findings reported by the API
on the mouse lymphoma assay must also be regarded as being of
questionable reliability for the following reasons:
a) Findings were observed to be inconsistent in multiple studies
conducted using the same test material;
b) Many findings reported as positive were, on inspection of the report,
weak or questionable;
c) Positive findings were obtained in some cases both with and without
S9 whereas in other cases the assay was positive only in the presence of
d) If metabolic activation by the standard method is inadequate for the
Ames assay, there is no reason to suppose that it would be adequate for
mammalian cell assays;
e) Positive findings in various mammalian cell in vitro assays at dose
levels producing a high degree of toxicity (as occurred in some the
tests reported here) were considered unreliable (Scott et al. 1991).
Findings indicate that VGOs/HGOs/Distillate fuel products containing
cracked materials may have some genotoxic potential. The degree of
activity is likely to be dependent on the amount of cracked material
present, the type of cracking involved and other factors.
Short description of key information:
The genotoxicity of members of the vacuum gas oil, hydrocracked gas oil
and distillate fuel category has been investigated in a number of
in-vitro and in-vivo studies. In-vitro studies include 13 bacterial
mutation assays, a mouse lymphoma assay and an SCE assay in Chinese
hamster ovary cells. Genotoxicity in-vivo has been investigated in 3
bone marrow cytogenicity studies and a male dominant lethal assay.
Although some ambiguous results were seen the majority of in-vitro
studies showed no, or little mutagenic activity. In the in vivo
micronucleus test home heating oil showed no evidence of genotoxic
activity. This lack of activity was supported by further in-vivo studies
including a male dominant lethal assay.
Endpoint Conclusion: No adverse effect observed (negative)
oil products containing relatively high concentrations of polycyclic
aromatic compounds (PAC) are considered genotoxic carcinogens, and,
consequently, are classified and labelled as carcinogenic, Cat. 1A or 1B
(H350) or Cat. 2 (H351) according to the EU CLP Regulation (EC)
1272/2008. This classification as carcinogenic does not automatically
imply that these substances need also to be classified as mutagenic as
defined by the CLP Regulation. The EU legislation aims primarily to
classify substances as mutagenic if there is evidence of producing
heritable genetic damage, i.e. evidence of producing mutations that are
transmitted to the progeny or evidence of producing somatic mutations in
combination with evidence of the substance or relevant metabolite
reaching the germ line cells in the reproductive organs. The PAC in oil
products are poorly bioavailable due to their physico-chemical
properties (low water solubility and high molecular weight), making it
unlikely that the genotoxic constituents can reach and cause damage to
germ cells (Roy, 2007; Potter, 1999). Considering their poor
bioavailability, oil products which have been classified as carcinogenic
do not need to be classified as mutagenic unless there is clear evidence
that germ cells are affected by exposure, consistent with the CLP
Regulation. For example, based on in vivo micronucleus tests on home
heating oil as well as for read-across substances that were all negative
for genotoxicity, vacuum gas oils/hydrocracked gas oils/distillate fuels
are not classified as mutagens according to the EU CLP Regulation (EC)
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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