Page 1030 - Basic _ Clinical Pharmacology ( PDFDrive )

1016 SECTION IX Toxicology

of this type are not currently classifiable as to carcinogenicity; they Other human effects are not clearly defined, although animal
are listed as IARC class 3. studies have shown toxic effects on immune, liver, and endocrine
function, and some increase in tumors and neonatal deaths. A
useful American Cancer Society fact sheet on the subject may be
Perfluorinated Compounds (PFCs) found at https://www.cancer.org/cancer/cancer-causes/teflon-and-

Fluorinated hydrocarbon chemicals have been of commercial perfluorooctanoic-acid-pfoa.html.
interest since the mid-20th century. Their uses have included
coolant materials in air conditioning systems; artificial oxygen- 2. Environmental toxicology—Perfluoro compounds are per-
carrying substances in experimental clinical studies; and heat-, sistent environmental chemicals having a broad environmental
stain-, and stick-resistant coatings for cookware, fabrics, and impact. PFOA and related compounds are now found widely
other materials. The fluorocarbons were produced in very large in water, soil, and many terrestrial and avian species. Aquatic
quantities and have become widespread in the environment. organisms have accumulated significant loads of PFCs. An
When it later became apparent that migration of lower molecular extensive risk assessment of the perfluoro chemicals has been
weight fluorocarbons to the troposphere had a deleterious effect carried out by Environment Canada, and guidelines have been
on the protective ozone layer, they were banned from use. The developed for the management of PFOA and related compounds.
higher molecular weight, more highly fluorinated compounds, These may be found at http://www.ec.gc.ca/ese-ees/default.
now called perfluorinated substances (eg, Teflon), have remained asp?lang=En&n=451C95ED-1.
in broad use. Like the heavily chlorinated and brominated hydro-
carbons, their commercial usefulness has been complicated by Endocrine Disruptors
a recognition of adverse environmental and suspected human As described above, the potential hazardous effects of some
toxic impacts that resemble some of the adverse qualities of chemicals in the environment are receiving considerable atten-
the other halogenated hydrocarbons. A useful reference is the tion because of their estrogen-like or antiandrogenic properties.
Centers for Disease Control and Prevention (CDC) fact sheet Compounds that affect thyroid function are also of concern.
on PFCs. It is found at https://www.cdc.gov/biomonitoring/pdf/ Since 1998, the process of prioritization, screening, and testing
PFCs_FactSheet.pdf. of chemicals for such actions has been undergoing worldwide
development. These chemicals mimic, enhance, or inhibit a
1. Human toxicology—Concerns about the toxicology of hormonal action. They include a number of plant constituents
PFCs have centered on their estrogenic properties and accumula- (phytoestrogens) and some mycoestrogens as well as industrial
tion and persistence in humans. Human exposure to perfluoro chemicals, persistent organochlorine agents (eg, DDT), PCBs,
compounds takes place through ingestion and inhalation. Since and brominated flame retardants. Concerns exist because of their
these compounds enter the food chain and water sources and are increasing contamination of the environment, the appearance of
persistent, ingestion of contaminated food and water products is bioaccumulation, and their potential for toxicity. In vitro assays
a major source of human accumulation. The human half-life of alone are unreliable for regulatory purposes, and animal stud-
PFOA is estimated to be about 3 years. As a persistent chemical ies are considered indispensable. Modified endocrine responses
and an endocrine disrupter, it is likely that it has some long-term in reptiles and marine invertebrates have been observed. In
adverse impact on reproductive function, cellular proliferation, humans, however, a causal relation between exposure to a spe-
and other cellular homeostatic mechanisms. Several PFCs (but cific environmental agent and an adverse health effect due to
not perfluoro compounds derived from PFOA) have been found endocrine modulation has not been fully established. Epidemio-
to act as proliferators of breast cancer cells. However, a large epi- logic studies of populations exposed to higher concentrations
demiologic study recently demonstrated a statistically significant of endocrine-disrupting environmental chemicals are underway.
association between high and very high serum PFOA levels in There are indications that breast and other reproductive cancers
workers and kidney cancer, and possibly prostate cancer, ovarian are increased in these patients. Prudence dictates that exposure
cancer, and non-Hodgkin’s lymphoma. There also may be mod- to environmental chemicals that disrupt endocrine function
est associations with cholesterol elevation and uric acid abnor- should be reduced.
malities. Finally, an acute pulmonary disorder, polymer fume
fever, is caused by the pyrolysis of PFOA. Like metal fume fever, Asbestos
seen in welders as a result of cadmium vaporization, polymer
fume fever has an acute onset several hours after exposure to the Asbestos in many of its forms has been widely used in industry
vaporized PFOA and may cause severe respiratory distress. The for over 100 years. All forms of asbestos have been shown to cause
onset of constitutional symptoms, malaise, chills and fever, and progressive fibrotic lung disease (asbestosis), lung cancer, and
respiratory distress is characteristic of fume fevers. While poly- mesothelioma. Every form of asbestos, including chrysotile asbes-
mer fume fever is usually mild and self-limited, noncardiogenic tos, causes an increase in lung cancer and mesothelioma. Lung
pulmonary edema has occurred. Whenever PFOA is heated cancer occurs in people exposed at fiber concentrations well below
above 350–400°C, toxic fumes capable of causing polymer fume concentrations that produce asbestosis. Very large-scale studies of
fever are emitted. Overheated household cookware or burning of insulation workers have shown that cigarette smoking and expo-
coated fabrics present this risk. sure to radon daughters increase the incidence of asbestos-caused