Metabolism and Toxicity of Hydrochlorofluorocarbons: Current Knowledge and Needs for the Future

Abstract

Hydrochlorofluorocarbons (HCFCs) are being developed as replacements for chlorofluorocarbons (CFCs) that deplete stratospheric ozone. The depletion of stratospheric ozone may increase the intensity of ultrviolet radiation at the earth's surface, which may be assodated with global, adverse human health effects. The greater tropospheric lability of HCFCs, which is due to the presence ofC-H bonds, reduces HCFC migration to the stratosphere; HCFCs should, therefore, cause less depletion of stratospheric ozone than CFCs. HCFCs under development include HCFC-22 (chlorodifluoromethane), HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane), HCFC-132b (1,2-dichloro-1,1-difluoroethane), HCFC-134a (1,1,1,2-tetrafluoroethane), HCFC-141b (1,-dich l-fluoroethane, and HCFC-142b (1-chloro-1,1-duoroethane). With the exception ofHCFC-22, which is already in use, the metabolism and toxicity ofHCFCs have not been studied in detail. By analogy to chlorinated ethanes, predictions can be made about the possible metabbolism ofHCFCs, but there are insufficient data available to predict rates of metabolism. Although most HCFCs appear to show low acute toxicity, some HCFCs are mutagenic in the Ames test. Hence, future researh on HCFCs should include studies on the in vivo and in vibo metabolism of HCFCs as well as on their toxicity in in ivo and in vitro systems.

Chemical Toxicology of Reactive Intermediates Formed by the Glutathione-Dependent Bioactivation of Halogen-Containing Compounds

“…The thioacyl halides formed from S-(1,1,2,2-tetrafluoroethyl)-L-cysteine covalently modify rat renal tubular proteins (42): Incubation of [ 35 S]S-(1,1,2,2-tetrafluoroethyl)-L-cysteine with renal tubular cells and analysis by 19 F NMR spectroscopy demonstrated the formation of N -(difluorothionoacetyl)lysine adducts (Scheme 1). Similarly, in rats given S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine or S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, covalently modified renal proteins were identified by 19 F NMR spectroscopy as N -(chlorofluorothionoacetyl)lysine or N -(difluorothionoacetyl)lysine adducts (43); renal proteins incubated with 2-chloro-1,1,2-trifluoroethyl 2-nitrophenyl disulfide, a proreactive intermediate that yields 2-chloro-1,1,2-trifluoroethanethiolate, also showed the formation of N -(chlorofluorothionoacetyl)lysine adducts.…”

Fatal Intoxication with 1,1-Dichloro-1-Fluoroethane

“…Among them, 1,1dichloro-1-fluoroethane is a potential substitute for trichlorofluoromethane (also known as CFC-11) in foam-blowing operations and as a cleaning agent in the computer industry. 2,4 We report a fatal intoxication involving 1,1-dichloro-1-fluoroethane.…”

“…During the past 25 years, previously fatal conditions, such as advanced testicular cancer, 2 Hodgkin's disease, 3 and childhood leukemia, 4 have become curable in more than 70 percent of cases, and up to 50 percent of patients with non-Hodgkin's lymphomas may now be cured. 5 Prospective, randomized trials have shown that postoperative (i.e., adjuvant) therapy leads to a 25 to 30 percent reduction in mortality among patients with locally advanced breast cancer 6 or colorectal cancer.…”

“…3 The study by Dr. Glaser and his colleagues is interesting, but most of their patients had acute, rather than chronic, heart failure. Even though Haber et al 4 concluded from their study of chronic heart failure that the "lack of discriminatory power [of the sedimentation rate] greatly limits the value of the test in the routine management of this disorder," they also state that their data "provide objective evidence . .…”

Winning the War on Cancer

“…During the past 25 years, previously fatal conditions, such as advanced testicular cancer, 2 Hodgkin's disease, 3 and childhood leukemia, 4 have become curable in more than 70 percent of cases, and up to 50 percent of patients with non-Hodgkin's lymphomas may now be cured. During the past 25 years, previously fatal conditions, such as advanced testicular cancer, 2 Hodgkin's disease, 3 and childhood leukemia, 4 have become curable in more than 70 percent of cases, and up to 50 percent of patients with non-Hodgkin's lymphomas may now be cured.…”