Asbestos Fibers and Other Elongate Mineral Particles: State of the ...

of these populations should be pursued if these
improvements are deemed feasible.
2.7.1.1.2 Animal Studies
The second element of NIOSH’s rationale for
recommending in 1990 that nonasbestiform
analogs of the asbestos minerals be encompassed
by the REL is related to evidence from
animal studies. Citing several original studies
and reviews [Stanton et al. 1977, 1981; Wagner
et al. 1982; Muhle et al. 1987; Pott et al. 1974,
1987; Lippmann 1988], NIOSH [1990a] concluded
that they provided evidence that fiber
dimension (and not fiber composition) was the
major determinant of carcinogenicity for mineral
fibers, stating that
Literature reviews by Lippmann [1988]
and Pott et al. [1987] enhance the hypothesis
that any mineral particle can induce
cancer and mesothelioma if it is sufficiently
durable to be retained in the lung and if
it has the appropriate aspect ratio and dimensions.
Similarly, Wagner [1986] concluded
that all mineral particles of a specific
diameter and length size range may
be associated with development of diffuse
pleural and peritoneal mesotheliomas.
That general conclusion notwithstanding, a study
by Smith et al. [1979] that was not cited by
NIOSH in 1990 addressed the specific question
of carcinogenicity of EMPs from nonasbestiform
amphiboles. Pleural tumor induction by intrapleural
(IP) injection challenge in hamsters was
compared for various challenge materials, including
two asbestiform tremolites and two
nonasbestiform (prismatic) tremolitic talcs. In
contrast to the two asbestiform tremolites, which
induced tumors in 22% and 42% of challenged
hamsters at the higher dose, no tumors resulted
following challenge with either of the two
NIOSH CIB 62 • Asbestos
nonasbestiform tremolites [Smith et al. 1979]. In
its rule-making, OSHA noted several limitations
of the study, including the small number of animals
studied, the early death of many animals,
and the lack of systematic characterization of fiber
size and aspect ratio [OSHA 1992]. One of
the nonasbestiform tremolitic talcs was later analyzed
and determined to have tremolitic chemical
composition and 13% “fibers,” as defined by
a 3:1 aspect ratio [Wylie et al. 1993].
Since 1990, another carcinogenicity study of
nonasbestiform amphibole minerals has been
published. An IP injection study in rats used six
samples of tremolite, including three asbestiform
samples that induced mesothelioma in 100%,
97%, and 97% of challenged animals [Davis et
al. 1991]. Two nonasbestiform tremolite samples
resulted in mesotheliomas in 12% and 5%
of the animals, and the response rate of 12% was
above the expected background rate. Another
sample that was predominantly nonasbestiform
but reported to contain a small amount of
asbestiform tremolite resulted in mesothelioma
in 67% of animals. Of note, the nonasbestiform
material associated with the 12% mesothelioma
incidence and this latter material contained an
approximately equal number of EMPs longer
than 8 μm and thinner than 0.5 μm.
Studies of in vitro assays of various biological
responses, some published before and
some after 1990, have also found relative toxicities
of asbestiform and non asbestiform
minerals that generally parallel the differences
observed in the in vivo IP injection studies
of tumorigenicity [Wagner et al. 1982;
Woodworth et al. 1983; Hansen and Mossman
1987; Marsh and Mossman 1988; Sesko and
Mossman 1989; Janssen et al. 1994; Mossman
and Sesko 1990] A recent review of the literature
concluded that low-aspect-ratio cleavage
31