Fluoroacetate-Mediated Toxicity of Fluorinated Ethanes

Keller, Douglas A.; Roe, Denko; Lieder, Paul H.

doi:10.1006/faat.1996.0058

“…Since CDFA is chemically very similar to TFA, these two substances may act through the same mode of action in Myriophyllum spp. Trifluoroacetic acid has been surmised to act through inhibition of aconitase in the citric acid cycle [5], as do other HAAs [17][18][19]. Previous studies with monofluoroacetic acid [18,19] showed a marked increase in concentrations of citrate in animal tissue and serum exposed to these HAAs.…”

Section: Introductionmentioning

confidence: 99%

“…Trifluoroacetic acid has been surmised to act through inhibition of aconitase in the citric acid cycle [5], as do other HAAs [17][18][19]. Previous studies with monofluoroacetic acid [18,19] showed a marked increase in concentrations of citrate in animal tissue and serum exposed to these HAAs. Currently, the hypothesis that TFA acts through the inhibition of the citric acid cycle does not seem feasible due to the apparent lack of either inorganic or organic means of degrading TFA, which would be required to produce the necessary halocitrate to inhibit the enzyme aconitase.…”

Section: Introductionmentioning

confidence: 99%

Chlorodifluoroacetic Acid Fate and Toxicity to the Macrophytes Lemna Gibba, Myriophyllum Spicatum, and Myriophyllum Sibiricum in Aquatic Microcosms

Hanson¹,

Sibley²,

Mabury³

et al. 2001

Environ Toxicol Chem

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Chlorodifluoroacetic acid (CDFA) is a novel haloacetic acid (HAA) and has been recently documented in aquatic systems. It is a suspected degradation product of the refrigerants 1,1,2-trichloro-1,1-difluoroethane (CFC-113) and 1-chloro-1,1-difluoroethane (HCFC-142b). Haloacetic acids can be phytotoxic, putatively acting through inhibition of the citric acid cycle. Replicate (n = 3) 12,000-L model aquatic ecosystems (microcosms) were dosed once at 0.5, 1, 5, and 20 mg/L of neutralized CDFA. Three microcosms served as controls. Each microcosm was stocked with eight individual apical shoots of both Myriophyllum spicatum and Myriophyllum sibiricum and sampled at regular intervals over a 42-d exposure period. The plants were assessed for the somatic endpoints of plant length, root growth, node number, and wet and dry mass and the biochemical endpoints of chlorophyll-a/b and carotenoid content as well as citric acid levels. The duckweed Lemna gibba was also introduced into these systems and monitored over a period of 14 d for wet/dry mass, plant/frond number, chlorophyll content, and growth rate. Concentrations of CDFA remained constant in the water column over the course of the fate investigation (241 d), indicating that this compound undergoes little, if any, degradation in aquatic systems. Results showed few statistically significant differences from controls for all three plant species with exposure to CDFA but no biologically relevant impacts. Overall, CDFA does not appear to pose any risk to these aquatic macrophytes at current environmental concentrations.

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“…Rats exposed to 3000 ppm DFE for 4 h showed no signs of adverse effect [ 11 ]. The substance may, however, induce cardiac sensitization at higher exposure levels (150,000 ppm).…”

Section: Introductionmentioning

confidence: 99%

1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling

Huet

¹

,

Johanson

²

2020

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(1) Background: Inhalant abuse and misuse are still widespread problems. 1,1-Difluoroethane abuse is reported to be potentially fatal and to cause acute and chronic adverse health effects. Lab testing for difluoroethane is seldom done, partly because the maximum detection time (MDT) is unknown. We sought to reliably estimate the MDT of difluoroethane in blood after inhalation abuse; (2) Methods: MDT were estimated for the adult male American population using a physiologically based pharmacokinetic (PBPK) model and abuse patterns detailed by two individuals. Based on sensitivity analyses, variability in huffing pattern and body mass index was introduced in the model by Monte Carlo simulation; (3) Results: With a detection limit of 0.14 mg/L, the median MDT was estimated to be 10.5 h (5th–95th percentile 7.8–12.8 h) after the 2-h abuse scenario and 13.5 h (10.5–15.8 h) after the 6-h scenario. The ranges reflect variability in body mass index and hence amount of body fat; (4) Conclusions: Our simulations suggest that the MDT of difluoroethane in blood after abuse ranges from 7.8 to 15.8 h. Although shorter compared to many other drugs, these MDT are sufficient to allow for testing several hours after suspected intoxication in a patient.

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“…Since CDFA is chemically very similar to TFA, these two substances may act through the same mode of action in Myriophyllum spp. Trifluoroacetic acid has been surmised to act through inhibition of aconitase in the citric acid cycle [5], as do other HAAs [17–19]. Previous studies with monofluoroacetic acid [18, 19] showed a marked increase in concentrations of citrate in animal tissue and serum exposed to these HAAs.…”

Section: Introductionmentioning

confidence: 99%

“…Trifluoroacetic acid has been surmised to act through inhibition of aconitase in the citric acid cycle [5], as do other HAAs [17–19]. Previous studies with monofluoroacetic acid [18, 19] showed a marked increase in concentrations of citrate in animal tissue and serum exposed to these HAAs. Currently, the hypothesis that TFA acts through the inhibition of the citric acid cycle does not seem feasible due to the apparent lack of either inorganic or organic means of degrading TFA, which would be required to produce the necessary halocitrate to inhibit the enzyme aconitase.…”

Section: Introductionmentioning

confidence: 99%

Chlorodifluoroacetic acid fate and toxicity to the macrophytesLemna gibba, Myriophyllum spicatum, andMyriophyllum sibiricumin aquatic microcosms

Hanson

¹

,

Sibley

²

,

Mabury

³

et al. 2001

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

Chlorodifluoroacetic acid (CDFA) is a novel haloacetic acid (HAA) and has been recently documented in aquatic systems. It is a suspected degradation product of the refrigerants 1,1,2-trichloro-1,1-difluoroethane (CFC-113) and 1-chloro-1,1-difluoroethane (HCFC-142b). Haloacetic acids can be phytotoxic, putatively acting through inhibition of the citric acid cycle. Replicate (n = 3) 12,000-L model aquatic ecosystems (microcosms) were dosed once at 0.5, 1, 5, and 20 mg/L of neutralized CDFA. Three microcosms served as controls. Each microcosm was stocked with eight individual apical shoots of both Myriophyllum spicatum and Myriophyllum sibiricum and sampled at regular intervals over a 42-d exposure period. The plants were assessed for the somatic endpoints of plant length, root growth, node number, and wet and dry mass and the biochemical endpoints of chlorophyll-a/b and carotenoid content as well as citric acid levels. The duckweed Lemna gibba was also introduced into these systems and monitored over a period of 14 d for wet/dry mass, plant/frond number, chlorophyll content, and growth rate. Concentrations of CDFA remained constant in the water column over the course of the fate investigation (241 d), indicating that this compound undergoes little, if any, degradation in aquatic systems. Results showed few statistically significant differences from controls for all three plant species with exposure to CDFA but no biologically relevant impacts. Overall, CDFA does not appear to pose any risk to these aquatic macrophytes at current environmental concentrations.

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Fluoroacetate-Mediated Toxicity of Fluorinated Ethanes

Cited by 38 publications

References 10 publications

Chlorodifluoroacetic Acid Fate and Toxicity to the Macrophytes Lemna Gibba, Myriophyllum Spicatum, and Myriophyllum Sibiricum in Aquatic Microcosms

Chlorodifluoroacetic Acid Fate and Toxicity to the Macrophytes Lemna Gibba, Myriophyllum Spicatum, and Myriophyllum Sibiricum in Aquatic Microcosms

1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling

Chlorodifluoroacetic acid fate and toxicity to the macrophytesLemna gibba, Myriophyllum spicatum, andMyriophyllum sibiricumin aquatic microcosms

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