observed in male rats in studies of saccharine, NTA (a detergent ingredient) and
melamine; forestomach tumors in rats
such as those induced by inhalation exposure to butoxyethanol, an ingredient in
oil dispersants used in the Gulf of Mexico
following the Deepwater Horizon spill;
kidney tumors observed in male rats, notably those induced by inhalation of
gasoline; and thyroid tumors (which are
ignored in order to discount the risks of
Most far reaching was the assertion
that lung tumors observed in rats after
inhalation of particles were not relevant
to people because these studies were
compromised by “overwhelming lung
clearance mechanisms.” These recommendations were intended to abort risk
assessments for carbon black and titanium dioxide.
Heinrich, U., R. Fuhst, et al.: “Chronic Inhalation Exposure of Wistar Rats and Two
Different Strains of Mice to Diesel Engine Exhaust, Carbon Black, and Titanium
Dioxide.” Inhalation Toxicology
7( 4):533–556 (1995).
Lee, K. P., H. J. Trochimowicz, et al.: “Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years.” Toxicol. Appl. Pharmacol. 79(2):
Mauderly, J. L., R. K. Jones, et al.: “Diesel exhaust is a pulmonary carcinogen in
rats exposed chronically by inhalation.” Fundam. Appl. Toxicol.
9(2): 208–221 (1987).
Muhle, H., B. Bellmann, et al.: “Pulmonary response to toner upon chronic inhalation exposure in rats.” Fundam. Appl. Toxicol.
17(2): 280–299 (1991).
Nikula, K. J., M. B. Snipes, et al.: “Comparative pulmonary toxicities and carcino-genicities of chronically inhaled diesel exhaust and carbon black in F344 rats.”
Fundam. Appl. Toxicol.
25(1): 80–94 (1995).
The carcinogenicity of carbon black and
titanium dioxide in laboratory studies
plays into the nanosafety dialogue. These
results inform assessment of diesel particulate matter (DPM). Even more broadly,
the question is whether “poorly soluble
low-toxicity” (PSLT) particles, which have
been misnamed “nuisance” particulate,
pose a cancer or respiratory risk.
DPM was reported to cause mutations
in bacterial bioassays as early as 1979.
This was correctly taken as an indication
of carcinogenic potential, and EPA soon
limited diesel emissions. I’m not aware of
any other public health action taken as a
result of a bacterial bioassay. The first
American report of lung tumors in rats
following DPM inhalation was published
in 1987. DPM was much more potent than
cigarette smoke (see “Smoke Gets in Your
Eyes,” October 2009 Synergist, p. 32). It
appears that inhalation bioassays for carbon black—considered to be the carbon
core of DPM with the polynuclear aromatic hydrocarbons washed away—were
launched to explain away the diesel results. Bioassays of pigment-size and nano-size titanium dioxide were also conducted.
Titanium dioxide was then considered of
no toxic potential and thus a negative
control. By 1995, published results showed
that carbon black and both fine and ultrafine (nanograde) titanium dioxide caused
lung cancer in rats. Somehow, the identification of carcinogenic potential of these
particles previously of low concern was
transformed into an argument that DPM
carcinogenicity could be discounted.
The “lung overload” hypothesis was ad-
vanced to support a threshold model for
risk assessment. A threshold model pre-
dicts that there is a dose level below which
no dose-response relationship exists.