Subchronic Inhalation Toxicity Studies with Hydrochlorofluorocarbon 123 (HCFC 123)

Rusch, George M.; Trochimowicz, Henry J.; MALLEY, LINDA J.; Kelly, David P.; Peckham, John; Hansen, John F.; Charm, Joel B.

doi:10.1006/faat.1994.1095

Cited by 27 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microscopic examination found centrilobular hepatocyte enlargement and vacuolation at the two highest levels and hepatocyte enlargement at 100 ppm. This observation is consistent with effects typically reported for compounds inducing peroxisome proliferation and has been reported previously (Rusch, 1994). There were no other treatment-related effects.…”

Section: Discussionsupporting

confidence: 93%

“…Typically, as the number of fluorine atoms increases, the toxicity decreases. This can be seen by a comparison of the subchronic toxicity of these three compounds (Rusch et al, 1994;Malley et al, 1995;Kawano et al, 1995). HCFC 123, being the most biologically active compound in this series, was selected as a surrogate for all three compounds for evaluation of reproductive toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…As prior 300, and 1000 ppm exposure level groups (Table 8). In the studies (Rusch et at, 1994;Malley et al, 1995) as well as Chol.…”

Section: Two-generation Reproduction Studymentioning

confidence: 98%

“…HCFC 123 was one of the first and most extensively studied materials. The first publication in this series (Rusch et al, 1994) described the results of a series of subchronic inhalation toxicity studies. Briefly, exposures were conducted with vapor concentrations of 300 to 20,000 ppm, 6 hr per day, 5 days per week for either 4 or 13 weeks.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Inhalation Teratology and Reproduction Studies with 1, 1-Dichloro-2,2,2-Trifluoroethane(HCFC-123)

Malinverno¹,

Rusch²,

Millischer³

et al. 1996

Toxicol Sci

View full text Add to dashboard Cite

HCFC 123 is one of the chemicals being developed as a replacement for CFC 11 in refrigerant and solvent applications. Supplementing earlier rat teratology studies, a rabbit inhalation teratology study was conducted. In addition, one-generation and twogeneration inhalation reproduction studies were conducted. In the teratology study, the pregnant rabbits were exposed to levels of 0 (control), 500, 1500, and 5000 ppm, 6 hr per day from Days 6 through 18 of gestation. Slight body weight losses and reduced food consumption were seen in does in all three exposure level groups. This response followed an exposure-related pattern. There were no other signs of maternal toxicity. There was also no evidence of treatment-related effects on the kits. A probe one-generation reproduction study was conducted. In this study four groups of 12 male and 12 female rats were exposed to vapors of HCFC 123 6 hr per day, 7 days per week from 4 weeks prior to mating through weaning of their offspring. The exposure levels for this study were 0 (control), 300, 1000, and 5000 ppm. There were no effects on mating and fertility, or on pup survival or birth weight. A two-generation study was subsequently conducted. In this study, five groups of 32 male and female rats were exposed to HCFC 123 from 6 weeks of age through weaning. From the offspring of these animals, groups of 28 males and females were selected for the F, generation. These animals were exposed to HCFC 123 from weaning (4 weeks of age) through weaning of the F, generation. All exposures were 6 hr per day, 7 days per week. The exposure levels for this study were 0 (control), 30, 100, 300, and 1000 ppm. There were no effects on any of the fertility or reproductive indices measured. As with prior studies, decreases in serum triglyceride levels were seen. Pup survival and birth weight were unaffected by treatment. Pup body weight gain was lower in all treatment groups during nursing, following an exposure-related pattern.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

“…As prior 300, and 1000 ppm exposure level groups (Table 8). In the studies (Rusch et at, 1994;Malley et al, 1995) as well as Chol.…”

Section: Two-generation Reproduction Studymentioning

confidence: 98%

mentioning

confidence: 99%

See 2 more Smart Citations

Inhalation Teratology and Reproduction Studies with 1, 1-Dichloro-2,2,2-Trifluoroethane(HCFC-123)

Malinverno¹,

Rusch²,

Millischer³

et al. 1996

Toxicol Sci

View full text Add to dashboard Cite

show abstract

“…These reviews concluded that HCFC-123 has a rather low order of acute inhalation toxicity in animals, the primary toxic effect being central nervous system depression. Nevertheless, several of these studies reported adverse effects on a number of physiological, biochemical and histologic parameters, particularly in the liver, following either single acute or repeated exposure to HCFC-123 (Marit et al 1994;Rush et al 1994). HCFC-123 has also been reported to have a tumorigenic effect (Malley et al 1995), which has been related to the peroxisome proliferation activity (Rush et al 1994).…”

mentioning

confidence: 99%

Bioactivation and Cytotoxicity of 1,1‐Dichloro‐2,2,2‐trifluoroethane (HCFC‐123) in Isolated Rat Hepatocytes*

Ferrara

Zanovello

Bortolato

et al. 2001

Pharmacology & Toxicology

View full text Add to dashboard Cite

Abstract:The bioactivation and cytotoxicity of 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123), a replacement for some ozone-depleting chlorofluorocarbons, were investigated using freshly isolated hepatocytes from non-induced male rats. A time-and concentration-dependent increase in the leakage of lactate dehydrogenase and a concentration-dependent loss of total cellular glutathione were observed in cells incubated with 1, 5 and 10 mM HCFC-123 under normoxic or hypoxic (about 4% O 2 ) conditions. Lactate dehydrogenase leakage was completely prevented by pretreating the cell suspension with the free radical trapper N-t-butyl-a-phenylnitrone. The aspecific cytochrome P450 (P450) inhibitor, metyrapone, totally prevented the lactate dehydrogenase leakage from hepatocytes, while two isoform-specific P450 inhibitors, 4-methylpyrazole and troleandomycin (a P450 2E1 and a P450 3A inhibitor, respectively), provided a partial protection against HCFC-123 cytotoxicity. Interestingly, pretreatment of cells with glutathione depletors, such as phorone and diethylmaleate, did not enhance the HCFC-123-dependent lactate dehydrogenase leakage. Two stable metabolites of HCFC-123, 1-chloro-2,2,2-trifluoroethane and 1-chloro-2,2-difluoroethene, were detected by gas chromatography/mass spectrometry analysis of the head space of the hepatocyte incubations carried out under hypoxic and, although at a lower level, also normoxic conditions, indicating that reductive metabolism of HCFC-123 by hepatocytes had occurred. The results overall indicate that HCFC-123 is cytotoxic to rat hepatocytes under both normoxic and hypoxic conditions, due to its bioactivation to reactive metabolites, probably free radicals, and that P450 2E1 and, to a lower extent, P450 3A, are involved in the process.

show abstract

Organic Chlorofluoro Hydrocarbons

Gadagbui,

Onyema

2023

Patty's Toxicology

View full text Add to dashboard Cite

This chapter is about organic chlorofluoro hydrocarbons, which are fully or partly halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F). In the early 1930s, chlorofluorocarbons (CFCs) were introduced in the 1930s as “safe” replacements for refrigerants such as sulfur dioxide, ammonia, carbon tetrachloride, and chloroform. The list was later expanded during World War II to include their use to produce insecticide aerosols to protect the troops in tropical areas against malaria and other insect‐borne diseases. Current usages include foam blowing, precision cleaning, and propellants for medicinal, cosmetic, and general‐purpose aerosols, air conditioning, and refrigeration. The expanded use of these CFCs has resulted in their emissions into the atmosphere. The CFCs have low chemical reactivity, long atmospheric lifetime, and are globally distributed. However, since they are ozone‐depleting and are also powerful greenhouse gases (GHGs), development was initiated to replace them with comparatively less ozone‐depleting and less greenhouse‐warming hydrochlorofluorocarbons (HCFCs). Subsequently, hydrofluorocarbons (HFCs) were developed that were both less ozone‐depleting and less GHGs accumulating. Both CFCs and HCFCs are controlled under the Montreal Protocol. The widespread use concerns about their environmental and human health effects of these substances have been extensively reviewed. This chapter updates information on the health effects of some of the major and minor CFCs, HCFCs, and HFCs, their global emissions estimates, the discrepancies, if any, between the major reporting regions and the global atmospheric emissions values, and the likely sources of the gap between the atmospheric measurements and the reported emissions.

show abstract

Subchronic Inhalation Toxicity Studies with Hydrochlorofluorocarbon 123 (HCFC 123)

Cited by 27 publications

References 0 publications

Inhalation Teratology and Reproduction Studies with 1, 1-Dichloro-2,2,2-Trifluoroethane(HCFC-123)

Inhalation Teratology and Reproduction Studies with 1, 1-Dichloro-2,2,2-Trifluoroethane(HCFC-123)

Bioactivation and Cytotoxicity of 1,1‐Dichloro‐2,2,2‐trifluoroethane (HCFC‐123) in Isolated Rat Hepatocytes*

Organic Chlorofluoro Hydrocarbons

Contact Info

Product

Resources

About