Abstract
Sodium fluoroacetate (1080) is a highly toxic metabolic poison that has the potential because of its lack of defined color, odor, and taste and its high water solubility to be intentionally or unintentionally ingested through food adulteration. Although the mechanism of action for 1080 has been known since the 1950's, no known antidote exists. In an effort to better understand the cardiopulmonary impacts of 1080, we utilized whole-body plethysmography and telemeterized Sprague-Dawley rats which allowed for the real-time measurement of respiratory and cardiac parameters following exposure using a non-invasive assisted-drinking method. Overall, the animals showed marked depression of respiratory parameters over the course of 24 hours post-exposure and the development of hemorrhage in the lung tissue. Tidal volume was reduced by 30% in males and 60% in females at 24 hours post-exposure, and respiratory frequency was significantly depressed as well. In telemeterized female rats, we observed severe cardiac abnormalities, highlighted by a 50% reduction in heart rate, 75% reduction in systolic blood pressure, and a 3.5-fold lengthening of the QRS interval over the course of 24 hours. We also observed a reduction in core body temperature of nearly 15°C. Our study was able to describe the severe and pronounced effects of sodium fluoroacetate poisoning on cardiopulmonary function, the results of which indicate that both tissue specific and systemic deficits contribute to the toxicological progression of 1080 intoxication and will need to be accounted for when developing any potential countermeasure for 1080 poisoning.
Highlights
Sodium fluoroacetate (1080) is a colorless, odorless, tasteless, water-soluble metabolic poison that inhibits the citric acid cycle and reduces the rate of cellular metabolism (Goncharov, 2009; Parton, 2013)
When administered a 0.85 LD50 dose of 1080, the median times for onset of convulsions were 85 ± 21 min in males and 113 ± 5 min in females. Both male and female rats that survived to 24 h exhibited a significant decrease in body weight compared to control, with the exposed males’ body weights decreasing 8.9 ± 1.4% (p < 0.05, Student’s t-test, n = 13–18) and females’ weights decreasing 6.7 ± 1.2% (p < 0.05, Student’s t-test, n = 4–5)
We did not observe any significant change in Anion gap (AG) (16.8 ± 3.6 mmol/L in controls vs. 15.1 ± 2.6 mmol/L in exposed), which is a typical indicator of metabolic acidosis (Zingg, Bhattacharya, & Maerz, 2018)
Summary
Sodium fluoroacetate (1080) is a colorless, odorless, tasteless, water-soluble metabolic poison that inhibits the citric acid cycle and reduces the rate of cellular metabolism (Goncharov, 2009; Parton, 2013). The United States tightly regulates the availability of the extremely toxic 1080 to sheep and goat farmers for managing coyote predation (Parton, 2013; Services, 2010), other nations, including Australia, New Zealand, Mexico, Japan, South Korea, and Israel, use it as a rodenticide to control invasive and nuisance mammals (Eason, 2002; Proudfoot, Bradberry, & Vale, 2006; Sherley, 2007). In March 2015, eco-terrorists in New Zealand threatened to poison infant and other dairy formula with 1080 due to their Department of Conservation’s controversial use of the chemical for pest control (Brockett & Withers, 2015; Cooney, Varelis, & Bendall, 2016; Hume, 2015).
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