Million Dollar Jury Award in Equitrol Lawsuit; Farnam Plans Appeal
(Updated Story) A jury awarded $1,007,500 to plaintiffs who alleged in a lawsuit that Farnam's Equitrol, a feed-through fly control product, was defectively designed and caused harm to their Thoroughbred and Warmblood sport horses. Farnam countered with a press release stating that it is appealing the decision and believes that the court decision is incorrect on legal and factual grounds.
The jury in the three-week trial in Santa Ana, Calif., over which U.S. District Court Judge James V. Selna presided, ruled in Farnam's favor on another point, which was an allegation that the company intentionally misrepresented the product.
Equitrol's active ingredient tetrachlorvinphos (TCVP, also known by the trade name Rabon; more on this later) is widely used by several companies in feed-through larvicides for cattle and horses and in fly control products for several other species. Equitrol has been available since 1983 and has been reported as effective in killing fly larvae in the manure before they have a chance to mature. According to Anne Robertson, Public Relations Director for Farnam Companies, both TCVP and Equitrol itself were recently re-registered by the Environmental Protection Agency (EPA). This was because several years ago, the EPA began the process of requiring all older pesticides that were registered with the EPA to go through another in-depth assessment.
Charlotte and Christopher Wrather, owners of Cottonwood Ranch in Los Alamos, Calif., and the ranch's manager/trainer Lori Akari, claimed that they fed Equitrol as directed, and that it caused or exacerbated a variety of health problems in their horses, "including reproductive problems and birth defects, stunted and retarded growth, hyperexcitability and other neurologic dysfunctions, laminitis, immunosuppression evidenced by unusual or unusually severe infections, 'low thyroid,' diarrhea, and colic."
Chris Jacobi, president of Farnam Horse Products, stated in a company release, "We stand by the product's safety and effectiveness reflected by its long-standing tenure in the marketplace. All of our products undergo extensive testing before they can become available to consumers and are designed to help horses and their owners."
Charlotte Wrather said that their horses were on Equitrol from 1996 through August 2000 during their area's fly season, which is from about April through November. During some parts of 1997 and 1998, she fed a different feed-through larvicide called Equifly. In the summer of 2000, she read an article in The Horse Journal that questioned the safety of feed-through fly control and decided to test her horses' cholinesterase levels (which is explained in a moment). "We tested the cholinesterase of selected horses while on Equitrol, discontinued the Equitrol, and tested again about eight weeks later," said Wrather, and she said they found that Equitrol significantly depressed serum cholinesterase levels in their horses.
Of the laundry list of problems listed earlier in this story, Wrather highlighted behavior problems, reproductive issues, and stunted growth in her interview with The Horse.
The behavior problems included "hyperexcitability in some horses rather like attacks, in others, rather like learning disabilities," according to Cottonwood information. "We won't get on one of these (affected) horses. That's how unpredictable they are," Wrather said. "One horse remembers what a halter is, the next day he doesn't."
The reproductive problems described to the jury were "delivery abnormalities such as dystocia and uterine inertia (failure of the uterus to contract correctly during labor), birth defects, angular (limb) deformities serious enough to require surgery, difficulty/inability in conceiving, abortion, and resorption," according to Cottonwood information. Wrather also said she noticed that when she took her six or seven yearlings off Equitrol that year, they had sudden growth spurts, suggesting to her that their growth had been stunted while on Equitrol.
Cholinesterase Inhibitors and Organophosphate Toxicity
Tetrachlorvinphos is an organophosphate cholinesterase inhibitor that generally is considered to have low mammalian toxicity.
"Acetylcholinesterase binds those enzymes that can metabolize or degrade the neurotransmitter acetylcholine," said Steven Nicholson, DVM, Dipl. ABVT, a veterinary toxicologist at Louisiana State University (LSU) and a livestock extension veterinarian with LSU's Ag Center. He explained, "When an animal gets a toxic dose (of organophosphate), that neurotransmitter accumulates at cholinergic nerve endings to organs and to what we call the neuromuscular junction." This accumulation of acetylcholine causes overstimulation of these nerve impulses. In other words, excess acetylcholine interferes with communication between nerves to organs and between nerves to muscle cells. (This is the mode by which TCVP targets and kills fly larvae--feed-through products with TCVP are designed so the TCVP passes through the digestive system of the mammal, being absorbed only minimally before being excreted in the manure where fly larvae reside.)
Nicholson added, "This eventually translates into clinical signs in an acutely poisoned animal that include diarrhea, shortness of breath, and sometimes excessive lacrimation (tearing). There also might be some signs of colic in the horse, muscle tremors that might actually proceed into convulsions, and perhaps excessive sweating."
Farnam's press release explained that although Equitrol is formulated to maximally pass through the animal's digestive system, as with most ingested substances, a minimal amount of the ingredient will be absorbed. It said that following Equitrol administration, a reduction in "whole blood cholinesterase" is expected in horses, but most of this drop is due to the greater decrease seen in plasma (the fluid around blood cells) compared to any decrease inside blood cells. "Both in-vivo and in-vitro studies have shown that this plasma cholinesterase activity is markedly more sensitive to TCVP and merely shows exposure to the ingredient, while blood cell and muscle cholinesterase activities were not affected," stated the release. (An Oklahoma State University study that is not yet published examined blood cell and muscle cholinesterase levels from which this statement is based.)
Nicholson explained, "There seems to be a better correlation between red cell cholinesterase (levels) and exposure than does the serum or so-called pseudo-cholinesterase. Most of us (toxicologists) like to get the red blood cell cholinesterase levels (as a measurement to ascertain poisoning).
"This product (TCVP) has been around a long time," added Nicholson. "I'd like to back up here and say that Rabon and these types of products are generally safe--you don't see any clinical adverse effects. I can't say I've seen a clinical case caused by ingestion of the products in any livestock species--which is not to say it doesn't happen."
How Much Is Toxic?
So exactly how much of a drop in cholinesterase in serum or blood signifies toxicity? The answer is not clear. Nicholson explained, "If you drew a blood sample and submitted it to the lab, typically you'd expect most (results from organophosphate-) poisoned horses to come back with cholinesterase levels less than, say, 25% of normal, or depressed 75%."
A July 2, 2002, memo from the EPA posted on the Cottonwood Ranch web site reviewing past TCVP research agreed with Nicholson's statement: "In an article in the veterinary literature, cholinesterase activity less than 50% of normal in the blood of horses is considered indicative of significant exposure to an anti-cholinesterase agent. Cholinesterase activity less than 25% of normal has been associated with cases of severe anti-cholinesterase poisoning."
John Madigan, DVM, MS, Dipl. ACVIM, professor of medicine and epidemiology and section chief of equine medicine at the Veterinary Medical Teaching Hospital at the University of California, Davis, testified as an expert witness in the case for the plaintiffs. He could not comment on the case directly, but reminded The Horse of comments on Equitrol that he had made during the Kester News Hour on Nov. 22, 2003, during the AAEP Convention in New Orleans, La. These included:
- Suspected adverse reactions to Equitrol reported by a horse owner in Texas prompted testing for blood cholinesterase levels. Whole blood cholinesterase levels had dropped by over 50% to a level, where when accompanied by clinical signs of organophosphate toxicity, are indicative of organophosphate poisoning.
- Data from a study in Oklahoma showed a drop in plasma cholinesterase, but no (drop in) red cell cholinesterase and no effect on muscle tissue acetylcholinesterase (with Equitrol usage).
- A UC Davis study (described below) revealed a substantial drop in whole blood cholinesterase in experimental horses fed Equitrol for 30 days.
- In pregnant mares and mares with foals which practice coprophagy (eating of feces), be very careful with feed-through fly control.
Madigan referred The Horse to the abstract of the Equitrol study that he and colleagues completed last year. It has not been published in peer-reviewed literature, so specific numbers are unavailable, but general conclusions were as he described during the Kester News Hour: That whole blood cholinesterase levels decreased significantly in response to TCVP feeding, indicating TCVP absorption. He and colleagues were not able to find any changes in cytokine or thyroid parameters during the trial in TCVP-fed or control animals. Behavioral testing revealed evidence of higher excitability in animals when they were on TCVP than when they were not. Madigan's team believes that additional studies are warranted to further understand the metabolic, immunologic, and behavioral effects of TCVP in horses. The study abstract can be found at www.vetmed.ucdavis.edu/ceh/info-EquitrolStudy-4-1-04.pdf
After looking at the UC Davis study abstract and studies cited by the EPA, Nicholson said, "(The UC Davis researchers) were trying to drive home the point that enough of this material was absorbed to actually have an effect systemically. That's a substantial drop (in whole blood cholinesterase levels), and clearly shows that they were exposed to an organophosphate."
In recent years, pediatricians have expressed concern about the possible effects of other cholinesterase-inhibiting insecticides used in agriculture and urban settings (sprays, fogs, and injectables for cracks and crevices in homes) on children's nervous system development, behavior disorders, and other subtle but lasting neurological effects. Nicholson does not recall studies relating to equine or livestock development in relation to cholinesterase inhibitors, specifically TCVP.
Warren Porter, PhD, of the Department of Zoology at the University of Wisconsin, Madison, was an expert witness in the case for the plaintiffs and could not comment on it directly. He explained his thoughts on organophosphate levels and toxic effects in horses: "Since there is typically no testing for immune, endocrine, or neurological effects, especially subtle effects on learning and behavior, in the physiological dose ranges where responses to the same chemical may be quite different than when given in high doses, horse owners may want to exercise caution in applying chemicals to their horses. It is important to realize that the current assumption of linear dose effects typically used in toxicology testing is being questioned by eminent endocrinologists whose data and theory suggest that up to 10,000-fold errors in estimating effects can be made using a linear dose assumption for very low doses of endocrine disrupting chemicals (Welshon et. al, Env. Health Persp., 2003)." In other words, the usual way to test compounds for toxicity is now being revised by top endocrinologists, and Porter feels the EPA registration process, which doesn't consider endocrine effects, might be seriously flawed for low-dose effects of these products.
"Surfactants and organic soaps present in various pesticides may promote their absorption into the blood through skin, respiratory surfaces, and the lacteals of the gut lining," Porter added. "These fat-soluble substances may cross membranes, such as the blood brain barrier and placental tissues. Thus, these biologically active molecules may gain access to the command and control center of the body and the developmental processes of a fetus in utero."
Porter explained that horse owners typically aren't dealing with a toxic dose of organophosphate, but a much lower level. "It is important to realize that hormone changes and responses to them and possibly organophosphates may take place in the parts per trillion in mammals, especially in fetuses," said Porter. "More and more chemicals are being identified as being hormonally active at very low levels."
He also explained that in humans, it has been shown that mutations in various defensive enzymes can alter their sensitivity to chemicals by altering the enzymes' ability to detoxify them. "Somewhere between one third and one half of the human population apparently is more susceptible to chemicals," he said. "I don't think it is known in horses yet whether similar mutations exist. Since they can occur in laboratory experimental animals, it is not unreasonable to suspect the same might be true in horses."
Addressing reproductive issues mentioned by the plaintiffs, "Farnam does not agree that there are any legitimate medical studies or any other medical literature demonstrating that the use of Equitrol on a pregnant or nursing mare would be harmful," said the Farnam release. "However, the company recommends that horse owners discuss with their personal veterinarians its use with specific horses and their particular situations."
Robertson added, "There is a pending labeling change which EPA has yet to finalize and implement for various products containing TCVP. In spite of rumors to the contrary, however, this pending labeling change will not warn against using TCVP-containing oral larvacides in pregnant and breeding mares. It will direct horse owners to consult their veterinarians before using on certain groups of animals, such as debilitated, aged, breeding, pregnant, or nursing animals.
"This is standard language that EPA brought over from FDA drug labeling in spite of the fact that, during this recent EPA assessment of the active ingredient, the EPA itself stated that 'there are no data from controlled studies which demonstrate that Equitrol causes or is associated with reproductive problems in horses and there are limited incident reports.' "
Farnam is required to report adverse events with EPA-registered products to the EPA. According to the July 2002 EPA memo, there had been three incident reports of reproductive problems in mares while being treated with Equitrol, with one of those concerning a horse with a history of failure to conceive or abortion.
According to Robertson, overall, "We get about a dozen calls a year--clarifications, questions, and concerns, which is pretty minimal."
The Clinical Vantage Point
Veterinarians affected horses included Mark Rick, DVM, and Greg Parks, DVM, of Alamo Pintado Equine Medical Center in Los Olivos, Calif., and David Jensen, DVM, of San Marcos Equine Practice in Los Alamos. They testified as percipient witnesses (a percipient witness is someone who testifies about what he or she observed in a particular situation).
Rick has treated the Wrathers' horses for at least 12 years and pulled records on 30-40 horses for the case. He strongly emphasized that as percipient witness, questions were never posed to him that would have him speculate or comment on the cause of problems in the Wrathers' horses, since he was not an expert witness. He was voluntarily available during the course of the trial to comment on the clinical signs, diagnoses, and treatment of horses. "I was on the farm, seeing the horses and treating and scratching my head about why some of the things were happening," he said.
"There was a variety of problems, which taken singly, would probably have not been that unusual," said Rick. "An abortion or stillborn foal, a mare that's difficult to get in foal, diarrhea, crooked legs, colic, laminitis, respiratory disease, a kind of unthriftiness, a little bit of spookiness, maybe a little stunted growth…Do you see these things on other farms? Absolutely. Do you see them on every farm you go to? No. Do you see them on farms with high numbers of horses? Yes. Could these problems only be caused by something bizarre that we'd never heard of or seen before? No, but the number of (unusual combinations of clinical signs in) cases that we saw in relation to the number of horses she had was excessive. We had no clue what was going on. It wasn't until after the fact that we finally realized that maybe there was an association between the fly control product and what was going on at the farm. That's when the experts came in.
"I came away (from the trial) feeling that what the Wrathers were doing, they weren't doing because they had an ax to grind or they wanted to make a lot of money. They did it because they thought that this might be the cause of their losses," said Rick. "That's what caused me to say I would even testify; I did it voluntarily because I did see problems (in their horses)."
Rick said that he has not seen a rash of problems like those at Cottonwood in any other clients' animals.
Wrather said, "It's not about us anymore--obviously a little of this is about us, and we may not have sued if we did not have economic loss. But this is really, at this point, about the horses. If I had my druthers, I wouldn't have anyone know I exist. But now I want this story as many places as we can get it."
It cannot be definitively proven whether or not Equitrol caused any or all of the problems in the Cottonwood horses because so little is understood about organophosphate toxicity. Farnam holds that more than 30 million doses have been administered since 1983 and that very few adverse events have been reported. The Wrathers believe Equitrol is the only thing that makes the problems with their horses add up.
Researchers are working to learn more about these chemicals and their effects on horses.
Porter said the take-home message for horse owners from this trial would be, "You have to live with the consequences of your decisions, and always consult with your veterinarian before using chemicals on your horses."
Porter said if horse owners would like to learn more about subtle biological effects of low-level mixtures of pesticides they can look at papers he and colleagues published in 1999 and in 2002 at www.wisc.edu/zoology/faculty/fac/Por/Por.html.
Web sites of the Defendant and Plaintiff:
- Organophosphates are contained in some feed-through fly control products for horses, cattle, and other species (including tetrachlorvinphos, TCVP, the active ingredient in Equitrol).
- Organophosphates can cause toxicity in mammals.
- Cholinesterase levels decrease in plasma and whole blood after organophosphates are absorbed by horses; plasma levels are more sensitive to the presence of organophosphates.
- No one knows how much organophosphate is needed to cause toxicity in horses.
- Unpublished research suggests that TCVP can cause behavior changes in horses.
- TCVP has been used as a larvacide in horses since 1983 under the name Equitrol.
- Very few adverse reactions have been reported to the federal government in association with TCVP administration in horses.
- Check with your veterinarian before using any medications in your horses, especially those which are debilitated, old, pregnant, or nursing.
About the Author
Stephanie L. Church, Editor-in-Chief, received a B.A. in Journalism and Equestrian Studies from Averett College in Danville, Virginia. A Pony Club and 4-H graduate, her background is in eventing, and she is schooling her recently retired Thoroughbred racehorse, Happy, toward a career in that discipline. She also enjoys traveling, photography, cycling, and cooking in her free time.