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EC number: 938-793-9
CAS number: -
The dermal carcinogenicity of 10 middle distillate samples was tested using undiluted test material. No treatment-related increase in tumours in internal organs was reported. It was noted by the authors that there was a significant increase in skin tumour yield with the majority of samples tested, but that non-neoplastic dermal changes including hyperplasia may have contributed to the tumourigenic response. In view of the questionable adequacy of the PAH analysis and the high levels of phenanthrene and pyrene found in some samples it is uncertain whether a genotoxic mechanism can be ruled out.
Fuels exhibited varying levels of activity in carcinogenicity testing
with some materials demonstrating low carcinogenic potential and others
a marked response both in the presence of severe irritation. Carcinogenic
activity is reported in the presence of repeated dermal irritation,
which could be prevented by limiting irritation. However, in view of the
questionable adequacy of the PAH analysis and the high levels of
phenanthrene and pyrene found in some samples tested in the key study,
it is uncertain whether a genotoxic mechanism can be ruled out.
VGO/Hydrocracked/Distillate fuels are classified as Category 2, H351, according
to the EU CLP Regulation (EC)1272/2008. This is in line with the
harmonized classification assigned to most of the members of the
category as in Annex VI of the regulation.
key carcinogenicity study (Biles et al. 1988; Klimisch = 2) was
identified to evaluate the carcinogenicity potential of vacuum gas oils.
this study, undiluted test material (25 µl) was applied three times
weekly to the shorn dorsal skin of groups of 40 or 50 male C3H/HeJ mice
for the lifetime of each animal or until all of the animals in the test
group developed grossly diagnosed carcinomas. There
were 10 different middle distillates tested, common names are provided
were two samples of commercial no. 2 heating oil (20% catalytic cracked)
with different boiling points. Virgin
heating oil blending base (straight run gas oil), Lightly refined
paraffinic oil (narrow cut acid-treated distillate fraction), Commercial
no. 2 heating oil (no cracked stocks), Commercial no. 2 heating oil (50%
cat. cracked), Commercial no. 2 heating oil (37% cat. cracked),
Commercial no. 2 heating oil (25% cat. cracked 75% coker liquids),
Commercial no. 2 heating oil (20% cat. cracked), Virgin heating oil
blending base+ catalytically cracked middle distillate (59%), Light
catalytic cycle oil (100% cat. cracked).
with a highly refined oil in the negative control groups produced no
tumours whereas the positive control group treated with catalytically
cracked clarified oil at concentrations of 1%, 3.3%, 20% and 25% showed
tumour incidences of 18%, 78%, 100% and 98% respectively, with time to
first tumour of 61, 37 16 and 17 weeks. Clear evidence of skin
irritation/skin injury was seen with all the test materials including
hyperplasia, hyperkeratosis, dermatitis, epidermal degeneration and
epidermal necrosis. Tumour incidences in internal organs were reported
to be sporadic and, except for hepatocellular carcinoma, to be of low
was noted by the authors that there was a significant increase in skin
tumour yield with the majority of samples tested, but that
non-neoplastic dermal changes including hyperplasia may have contributed
to the tumourigenic response.
Additional data support that
VGOs/HGOs/Distillate fuels are carcinogens (IIT
Research Institute, 1985; NTP, 1986; Witschi et al., 1987; Clark et al.,
1988; Gerhart et al., 1988; API, 1989; Broddle et al., 1996; Dally et
al., 1996; EMBSI, 1996; Nessel et al., 1998).
This information is presented in the dossier. Dally
et al., 1996; Nessel et al., 1998; and EMBSI, 1996 tested
hydrodesulphurised middle distillate in mice for up to 104 weeks.
Animals treated with straight run gas oil exhibited relatively slow
tumour growth in the presence of concurrent skin irritation, suggesting
tumour induction via a non-genotoxic mechanism. A
significantly elevated tumour incidence was also reported in mice
treated with hydrodesulfurised middle distillate (API, 1989 and Broddle
et al., 1996). The dermal carcinogenicity study conducted by IIT
Research Institute (1985) demonstrated that marine diesel fuel is
carcinogenic in mice (9 of 46 animals exhibited malignant tumours) while
a study conducted by NTP (1986) showed equivocal evidence
of carcinogenicity in male and female B6C3F1 mice. Witschi et al. (1987)
demonstrated that fuel oil (API fuel No. 2) had low tumourigenic
potential. Clark et al. 1988 and Gerhart et al. 1988 conducted dermal
carcinogenicity studies which indicate that diesel and furnace oil have
In deriving an overview of the
carcinogenicity of VGOs/HGOs/Distillate fuels it is important to
consider carcinogenicity studies on gas oil samples together with
information on their irritancy potential, and available evidence on
polycyclic aromatic hydrocarbon levels, genotoxicity data and other
mechanistic studies (e.g. initiation/promotion testing; modified Ames
The overall data available on gas oils
indicate that they produce severe dermal irritation when applied
repeatedly to the skin in neat form; observations made during most of
the studies reported draw attention to this. Histological examination
confirms epidermal necrosis, ulceration and dermal damage with
inflammatory changes are often seen together with marked acanthosis
(epidermal hyperplasia). While evidence suggests that dilution with a
volatile organic solvent does not reduce skin irritation appreciably,
the irritancy properties of gas oils and other middle distillates can be
reduced substantially by dilution with highly refined mineral oil. It is
evident that the level of skin irritation produced by neat gas oils
would probably be sufficient to produce skin tumours in mice by a
non-genotoxic mechanism, even in the absence of significant amounts of
genotoxic constituents. However in order to demonstrate that a
non-genotoxic process was responsible for skin tumour induction, it is
essential to show that the gas oils concerned do not contain significant
levels of genotoxic ingredients and produce a tumour response consistent
with that of a non-genotoxic substance (e.g. a tumour incidence of less
than 25% with a latent period in excess of 1 year).
Of the gas oil blends and products
containing cracked components that have been tested in long term skin
painting studies (n =18), the majority produced moderate incidences of
skin tumours, although in many instances no supporting information on
PAC content, modified Ames data or information on initiating/promotion
activity is available. Nonetheless, two samples containing cracked
material have been showed to exhibit some degree of initiating activity,
while analyses of 3-7 ring PACs and Mutagenicity Index data on these and
other samples not subject to mouse skin painting tests, are consistent
with the likelihood of a genotoxic mechanism. In view of this it is
probable that tumours produced by blends containing cracked components could
be linked to a genotoxic mechanism of action.
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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