Toxicological Sciences, Vol 49, 48-55, Copyright © 1999 by Society of Toxicology
CS Nessel, JJ Freeman, RC Forgash and RH McKee
Petroleum middle distillates (PMDs), a class of hydrocarbons which boil
between 350-700 degrees F, are tumor promoters in mouse skin. The
promotional activity is produced under conditions that also result in local
changes, including chronic irritation and epidermal hyperplasia. The
present study was conducted by comparing equal weekly doses of irritating
and minimally or nonirritating test materials, to assess whether tumor
promotion was a secondary response to these effects. Four PMDs, C10-C14
normal paraffins (NP), lightly refined paraffinic oil (LRPO), Jet Fuel A
(JF), and steam-cracked gas oil (SCGO), were evaluated. Test materials were
applied undiluted (2x/week) or as 28.6% (7x/week) or 50% (4x/week)
concentrations in mineral oil for 52 weeks following initiation with
dimethylbenzanthracene (DMBA). When applied undiluted, all materials
produced moderate irritation and significant increase in tumor incidence.
When NP, LRPO, or JF were applied in mineral oil diluent, skin irritation
was generally ameliorated and few, if any, tumors were produced. SCGO was
irritating and produced a significant increase in tumor frequency when
administered in mineral- oil diluent. These data indicate that the
promotional activity of straight-run PMDs is likely related to chronic
irritation at the application site and not to dose. Thus, when used
appropriately in the absence of prolonged irritation, these materials
should not present a tumorigenic hazard to humans.
ARTICLES
The role of dermal irritation in the skin tumor promoting activity of petroleum middle distillates
Exxon Biomedical Sciences, Inc., East Millstone, New Jersey 08875-2350, USA.
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