Middle distillate from refinery proces cofeeding vegetable oil

Carcinogenicity

Description of key information

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.

Justification for classification or non-classification

VGO/Hydrocracked/Distiallate 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.

 

Therefore 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.

Additional information

One key carcinogenicity study (Biles et al. 1988; Klimisch = 2) was identified to evaluate the carcinogenicity potential of vacuum gas oils.

In 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 below. There 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).

 

Treatment 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 frequency.

 

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.  

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 carcinogenic potential.

Summary

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 test).

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.