Assessment of the morphology and significance of the lymph nodal and hepatic lesions produced in rats by the feeding of certain mineral oils and waxes - Proceedings of a pathology workshop held at the Fraunhofer Institute ofToxicology and Aerosol Research Hannover, Germany, May 7-9, 2001
Ww. Carlton et al., Assessment of the morphology and significance of the lymph nodal and hepatic lesions produced in rats by the feeding of certain mineral oils and waxes - Proceedings of a pathology workshop held at the Fraunhofer Institute ofToxicology and Aerosol Research Hannover, Germany, May 7-9, 2001, EXP TOX PAT, 53(4), 2001, pp. 247-255
A Panel of medical and veterinary pathologists reviewed published and unpub
lished reports dealing with studies of various white mineral oils and waxes
in F344 and Sprague-Dawley rats. They also had available and studied histo
logic slides from both subchronic and chronic studies of certain mineral hy
drocarbons 90-day oral study of low melting point wax (LMPW) in female Fisc
her 344 and Sprague-Dawley rats; 90-day studies of P15H* and P70H white oil
and high melting point wax (HMPW) in male and female F344 rats and 24 mont
h study of P70H white oil in male and female F344 rats. The Panel also revi
ewed mineral oil-induced alterations in tissues of human patients (liver, h
epatic lymph node and spleen). The Panel agreed that certain of the mineral
hydrocarbons produced lesions in the mesenteric lymph nodes and liver of t
he F344 rat and these lesions were best described as microgranulomas/granul
omas. The lesions were fundamentally similar in both organs, although varyi
ng in severity with dose and type of mineral hydrocarbons. The Panel agreed
that hepatic lesions with inflammatory cell infiltration, necrosis, and fi
brosis were produced only by feeding of LMPW and the lesions were confined
to F344 rats and not found in Sprague-Dawley rats. The most severe granulom
atous lesions in the mesenteric lymph nodes were found in high dose LMPWfed
F344 rats. The microgranulomas were similar in subchronic and chronic stud
ies. Also, little difference existed between controls and treated F344 rats
in the incidence and severity of the lesions after 2 years of feeding P70H
white oil. The Panel agreed that some slight reversibility existed for the
se lesions, but also agreed that complete resolution was unlikely as regres
sion of the lesions in the rat would likely be slow. The Panel agreed that
a minimal severity infiltrate of mononuclear inflammatory cells occurred in
the base of the mitral valve in a slightly increased incidence in F344 rat
s fed LMPW. The Panel concluded that these mitral valve alterations had lit
tle if any toxicologic significance as the focal infiltrate was minimal in
severity, occurred in controls, occurred in association with murine cardiom
yopathy, and were unlike the responses in the liver and mesenteric lymph no
des. The Panel agreed that the lesions observed in the liver and mesenteric
lymph nodes of F344 rats exposed to MHCs, especially the LMPW, were differ
ent morphologically from changes observed in lymph node, liver, and spleen
of humans that were mineral oil-users, These changes in humans are usually
found incidentally in tissues taken at biopsy or autopsy. The MHC-induced l
esions can be considered incidental and inconsequential in humans.
Granulomatous lesions are produced in rats by MHC-feeding, especially in li
vers of the F344 rat with certain of the MHCs, but are not found in human t
issues. This suggests a heightened and perhaps different type of toxic resp
onse in the rat compared to humans. The MHC-associated alterations in human
s are ubiquitous, present after a certain age in most, if not all, humans,
and consist of intra-and extra-cellular oil droplets with a minimal macroph
age (including giant cells) response.