“Educating and Empowering"
With Holistic Actions! and home-opathy
Home is where healing happens best.
The original HomeVet© Since 1987



Is It Safe to Use Strong Chemicals to Kill Fleas and Ticks?

Tempting as it may be to simplistically consider fleas as horrible insects, the bane of cats and dogs everywhere, poisoning your cat or dog in a vain attempt to wipe fleas out of existence doesn’t really make sense.

Even though more than half a billion dollars annually are spent on products that kill fleas in that vain pursuit.

Of course fleas can make cats and dogs (and everyone else in the household) perfectly miserable. But it’s not as if using toxic flea-killing chemicals is the only way to control fleas. When we attempt to get rid of our animals’ fleas by utilizing chemicals that are toxic to the brain and nervous system, that may disrupt hormone (endocrine) systems, and that cause cancer, it’s sort of like burning the house down to get rid of ants – effective, sure, but what are you left with?

New flea and tick products not safer

All pesticides pose some degree of health risk to humans and animals. Despite advertising claims to the contrary, both over-the-counter and veterinarian-prescribed flea-killing topical treatments are pesticides that enter our cats’ and dogs’ internal organs (livers, kidneys), move into their intestinal tracts, and are eventually eliminated in their feces and urine. Not only that, but the humans and other household animals who closely interact with cats and dogs who have been treated with these chemicals can be affected by the toxins. What happens to the health of all exposed individuals during this systemic absorption and filtration process varies from animal to animal, but the laboratory and field trial results clearly indicate toxicity on the chronic and acute levels.

Until recently, foggers, flea collars, powders, sprays, shampoos, and dips containing organophosphates (chlorpyrifos, malathion, diazinon), pyrethrins, synthetic pyrethroids, and carbamates, were the cutting-edge solutions to our flea problems. They were effective, but unfortunately, they also caused disease and sometimes death. Given enough time, most pesticides eventually cause enough human and animal injuries that they are identified as hazards and are removed from the market.

While the newest flea products – so-called “spot-on” liquids that are applied monthly to a cats’ and dog’s skin – are being marketed aggressively by the manufacturers and veterinarians and represented as safe alternatives to their predecessors, the fact is, they are simply newer. All the “active” ingredients in these spot-on preparations – imidacloprid, fipronil, permethrin, methoprene, and pyriproxyfen – have been linked to serious health effects in laboratory animals (see chart at end of article).

“The public must recognize that any decision to use a pesticide, or to otherwise be exposed to pesticides, is a decision made in ignorance,” says Eliot Spitzer, Attorney General of the New York Environmental Protection Bureau. “We do not know the identity of the chemicals to which we are exposed. We cannot make informed individual decisions on the acceptability of those exposures, a basic element in the maintenance and protection of our own health.” Spitzer adds, “The requirements for marketing a new product fall considerably short of providing safety for our animal and human families.”

 Active and inert ingredients in flea and tick products:

To fully understand the risks associated with any of these products, it is important to understand the various components in a flea product, or any chemical product that you may prescribe in your veterinary practice, for that matter.

Like other chemical products, all flea products are made up of “active” and “inert” ingredients; strangely, the actual definitions of those phrases are very different from what they seem to connote. In the case of flea-killing chemicals, the “active” ingredient does, in fact, target and kill fleas – but some of the “inert” ingredients are poisons, too.

While the word “inert” suggests benign activity and even connotes safety in the minds of many veterinarians and lay people, legally, it simply means added substances that are not the registered “active” ingredient. This is important because most people assume that only the “active” ingredient in a chemical product is of concern. Many people feel comforted by the idea that a product contains only a minuscule amount of an “active” ingredient and up to 99.9 percent “inert” ingredients – a typical formula in many pesticide products. Actually, this makeup should frighten veterinarians and consumers a like.

Why? Because the Environmental Protection Agency (EPA, the government agency that oversees the pesticide industry) requires a higher (if not high enough) standard of scrutiny for “active” ingredients; these must undergo a battery of tests to determine their toxicological profiles, be registered with the EPA, and be listed on the product inserts and packaging. In contrast, “inert” ingredients need not be listed on the product inserts and packaging and are subject to much less testing than the “active” ingredients; “inerts” are generally tested in short-term studies for acute toxicity only.

The word “inert” implies chemicals that are somehow inactive. In actuality, many “inert” ingredients used in pesticides are as toxic, or more toxic, than the registered “active” ingredients. For example, naphthalene, one of the “inerts” in an imidacloprid product, showed clear evidence of cancer activity through inhalation (nasal cancers), as well as anemia, liver damage, cataracts, and skin allergies. An unidentified “inert” ingredient in the flea product Advantage was implicated in the death of kittens who received doses within laboratory tolerances.

Why don’t pesticide manufacturers have to disclose all the ingredients in their products? This kettle began brewing in 1949, when the U.S. Congress passed the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), allowing manufacturers confidentiality on issues they claimed would otherwise make them vulnerable to market competition. “Inert” ingredients, in other words, became protected by industry as “trade secrets.” While protecting industry, this act supersedes the public’s right-to-know to what we are being exposed and the health hazards resulting from these exposures. And without full disclosure, we are unable to make educated decisions as to which chemicals we want to avoid.

 Laboratory studies of chemicals used in flea and tick products

Obviously, products undergo testing in order to qualify for EPA registration, and presumably, most of the overt dangers a product can exert are ameliorated before the product can be marketed. Scientists use healthy, adult, genetically identical mammals to test pesticides, and then extrapolate health information regarding the safety of the product to domestic animals and human beings. In the case of flea products, the laboratory tests are performed on live mice, rats, cats, and dogs.

These toxicological studies are performed to establish the LD 50 – the oral dose at which the product would kill 50 percent of a test population – and to determine the acute and chronic effects. Throughout and following the test, subjects are killed in order to study the specific system damage (lungs, kidney, etc.). Acute disease tests, such as nervous system and skin reactions, can be performed over a relatively short time period. Most studies are conducted for 3-, 13-, or 52-week intervals, and use exaggerated dosages to compensate for the short testing periods.

“Because of the short period under which the studies are conducted, the health effects resulting from the higher doses of the chemicals are relevant,” says veterinarian, Dr. Virginia Dobozy of the EPA’s Pesticide Division. These effects can include head-nodding; facial twitching; exaggerated blinking; gag responses; weight increase of the spleen, thymus, and adrenal glands; and/or atrophy of the thymus.

Long-term studies, needed to understand the chronic effects of the pesticides, are few by comparison. Chronic disease such as cancer, immune suppression, developmental or reproductive damage, and DNA damage can take months or years to manifest.  Since these studies are not required by the EPA in order for a new pesticide product to be registered, the registrant often does not include these in their budget, nor in their data to the US EPA for registration of their new pesticide.   “The cancer study for Frontline was terminated early”, says Dr. Dobozy, “due to excessive deaths early on in the experiments”.

However, the cumulative effect – potential damage from continued use of one specific pesticide product or multiple products over a cat’s or dog’s lifetime – is unknown. Also unknown is the potential for synergistic effects – combined impacts of chemical exposures from their home and outdoor environments. Neither the cumulative nor the synergistic effects of chemicals in products are required to be tested by the EPA before a product is made commercially available. So, our cats and dogs may be more vulnerable to unknown chemical-related dangers than the happy commercials and product literature would have you believe.

Critics of the pesticide industry claim that the EPA registers pesticides not on safety, but on a cost-benefit basis, balancing health and environmental concerns against the economic gain to the manufacturer and the end user of the product. But even if the pesticide manufacturers and the EPA are not overly concerned about our safety, we as veterinarians, consumers, and guardians should be very concerned.

Are the claims made for the newer flea and tick products too good to be true?

Today, spot-on flea preparations are considered by many as the Rolls Royce of flea products, and sell swiftly in veterinary clinics and pet stores. Each of the makers of these products claim that they are safe – safer than ever – and that only the targeted insects will be affected by the products’ neurotoxic impacts. The products are frequently advertised as safe for small children and adults as well as kittens (as young as eight weeks) and puppies (as young as seven weeks) and geriatric cats and dogs. Do they sound too good to be true? Well, perhaps they are.

The spot-on flea products fall into four general categories of insecticides. All have neurotoxic effects. The first three – imidacloprid (a chloro-nicotinyl insecticide), fipronil (a phenylprazole insecticide), and permethrin (a synthetic broad spectrum pyrethroid insecticide) – all work by disrupting the nervous system of insects, killing by contact or ingestion. The fourth type contains insect growth regulators (IGR), which don’t kill, but interrupt the flea’s life cycle.

Imidacloprid is the first of its class of insecticides, and is relatively new on the block; it was introduced in 1994. Laboratory testing on mice, cats, dogs, and rats, indicates that this insecticide can be neurotoxic to laboratory animals, causing incoordination, labored breathing, thyroid lesions, reduced birth weights, and increased frequency of birth defects.

Fipronil was introduced in the United States in 1996. It is a neurotoxin and suspected human carcinogen. Fipronil can cause liver toxicity, thyroid lesions (cancer), damage to the kidneys, increased cholesterol levels, alterations in thyroid hormones, incoordination, labored breathing, increased miscarriages, and smaller offspring.

In a review of the fipronil pet formulations, Dr. Virginia Dobozy of the EPA’s Pesticide Division states that “this is a persistent chemical that has the potential for nervous system and thyroid toxicity after long term exposure at low dosages.”

Permethrin, a synthetic broad spectrum pyrethroid insecticide, is suspected to be an endocrine disrupter and a carcinogenic insecticide (causing lung cancer and liver tumors in laboratory animals). Some permethrin products have additional “active” ingredients in lesser percentages, and include methoprene, and pyriproxyfen (described below).

Methoprene and pyriproxyfen are both insect growth regulators (IGR), which limit the development of juvenile fleas so they cannot reproduce. Test results indicate that methoprene causes enlarged livers and degeneration of parts of the kidneys.

All of the above active ingredients have induced responses in laboratory animals that give cause for alarm. While these new products are suggested as safer than their predecessors, they indicate high levels of acute and chronic poisoning from short-term use.

Method of action of spot-on flea products

Whether or not it is purposeful, manufacturers of these spot-on flea products have managed to convince many veterinarians and animal guardians that these products are not absorbed into our cats’ or dogs’ systems. The companies’ literature describes in vague and contradictory detail how the chemicals don’t go beyond the hair follicles and fat layers of the cats’ or dogs’ skin.

Take, for example, information published on Merial’s Web site for Frontline (“How Frontline Works”). In one place, it clearly states that fipronil (Frontline’s “active” ingredient) is absorbed into the skin (“Sebaceous glands provide a natural reservoir for Frontline . . .”), but other statements suggest that fipronil stays there and then leaves through the same entry point without moving into any other parts of the cat’s and dog’s body – an illogical conclusion.

When Dr. Dobozy reviewed the results of a fipronil metabolism study, she reported that “significant amounts of radio-labeled fipronil were found [not only] in various organs and fat  at 168 hours post-dosing for all dose groups . . . [but they were also] excreted in the urine and feces, and were present in other parts of the body—fat included . . . which demonstrated that the chemical is absorbed systemically.”

Veterinarians and animal guardians who pay close attention can witness evidence that these products are indeed systemically absorbed. Dr. Stephen Blake, a San Diego veterinarian, relates a client’s experience: “We put Advantage on the backs of our dogs and could smell it on their breath in a matter of minutes following the application.” Blake stated that this indication of immediate absorption did not tally with what he had been led to believe by reading Bayer’s literature. He continues to question its safety for his clients’ animals.

Neurological health effects of spot-on flea and tick products

Logic tells us that a topical chemical that is not absorbed into the skin has no chance of causing neurotoxic effects. Then why do the Material Data Safety Sheets (MSDSs) for all the permethrin-containing pesticides recommend preventing their products from having prolonged contact with the skin? And why do they all state that skin sensations, such as “numbness and tingling,” can occur? Schering-Plough’s MSDS makes an additional statement about its Defend EXspot Treatment: “can be harmful if absorbed through the skin and harmful following inhalation,” causing headaches, dizziness, and nausea.

Bayer does not reveal more than 90 percent of the ingredients in Advantage, but its MSDS does warn us to “use a respirator for organic vapors” in order to avoid “respiratory tract irritation and other symptoms such as headache or dizziness” (symptoms of nervous system exposure). Bayer’s promotional literature for Advantage, however, states that “studies prove that using 20-24 times the dosage on dogs and cats does not cause any internal or external side effects,” and that “. . . switching to Advantage from another flea control product poses virtually no risk to your pet.”

Dr. Graham Hines, a veterinarian from the United Kingdom, treated a four-year-old female German Shepherd who had two Advantage Top Spot treatments. He reported that “both times she became unusually clingy, and would not leave her guardian’s side, yet paced up and down all day, very restlessly. These symptoms persisted for 48 hours before a gradual return to her normal state.” The neurotoxic effects were clear to Dr. Hines.

Dr. Blake also finds different results than the Bayer literature. “We are told that the product affects only insects’ nervous systems, not mammals’. Several of my clients told me that they accidentally got some Advantage on their hands and when they touched their mouths, their lips became immediately numb for several hours. So much for not having an effect on the nervous system of mammals.”

Acute symptoms of headache, nausea, and abdominal and lumbar pain are associated with carbitol, one of the “inert” ingredients in Frontline. According to the MSDS, carbitol induced these symptoms in laboratory settings.

Curiously, these potential side effects are not published in the literature accompanying the products, nor do many veterinarians know the dangers. But there are hundreds of EPA incident reports as well as numerous anecdotal reports from veterinarians in the U.S. and the U.K. of cats and dogs who were treated with spot-on products who have displayed signs of neurological damage, such as depression, lethargy, convulsions, underactivity, tremors, overactivity, stiffened limbs, and lameness.

Adverse skin effects of spot-on flea and tick products

Topical skin irritation is listed on all the MSDSs of the products reviewed in this article; however, product literature inserts fail to emphasize the extreme nature of the problems. They all instruct the users that their products are for “external use only,” and to “avoid contact with the skin,” but only Merial’s product insert appears to suggest there is some possibility of adverse skin contact reactions.

Dr. Dee Blanco, a holistic veterinarian practicing in New Mexico, treated 20 dogs for adverse reactions to Farnam’s flea product. In a letter to the Farnam regarding a client who had used one of Farnam’s permethrin-based insecticides, Dr. Blanco stated, “All the dogs (20 out of her 24 dogs treated with BioSpot) had pruritus with bleeding and cracking of the skin, various degrees of erythema, many fluid vesicles, severe hair loss, and elephantiasis with chronic itching. Many also showed severe mental depression, lethargy, and symptoms concomitant with aggravated liver toxicity. All symptoms appeared within two weeks after applications of your (BioSpot) product, also a consistent time-frame for liver toxicity after absorption through the skin. . . To date, most of the dogs have dramatically improved but a few still remain symptomatic.”

Dr. Blanco also stated that one dog died of liver cancer within three months of this BioSpot application, which she says “could have been exacerbated by the application of BioSpot.” Permethrin is indicated as a possible carcinogen by the EPA, causing liver enlargement and cancers in laboratory mammals.

When Dr. Dobozy reviewed the reports from fipronil product studies, she found that Frontline “does not adequately describe the severe reactions” reported by veterinarians – sloughing, “chemical burn” conditions, and extensively affected areas well beyond the application site. When these incidents were reported, Merial recommended bathing the cats and dogs. That’s strange, because their literature indicates the product remains effective after bathing.

The MSDS for Bayer’s Advantage tell us that “prolonged contact with the skin can cause defatting of the skin due to solvent component in the products,” to “avoid skin contact,” “to wear appropriate gloves when handling the product,” and to “wash off any contamination.”

Chronic diseases and flea and tick products

Based upon toxicological studies, a dog suffering from liver, kidney, thyroid, adrenal, spleen, lung, brain or gonadal conditions could experience heightened states of chronic diseases, with the potential for development of cancer, when spot-on flea preparations are used. Permethrin is linked to malignant liver and lung tumors and autoimmune system disease, and at very low levels suppresses the immune system. Thyroid lesions have developed in laboratory studies in dogs during imidacloprid tests. Further studies are necessary to understand the possibilities of malignancy. Thyroid cancer has been linked to fipronil, according to the EPA. The data from the metabolism and chronic toxicity studies for fipronil indicate that “ . . . this is a persistent chemical and has the potential for nervous system and thyroid toxicity after long-term exposure at low levels,” according to Dr. Dobozy.

In the Journal of Pesticide Reform, author Caroline Cox cites studies that show thyroid sensitivity to imidacloprid can result in thyroid lesions, as well as increased incidences of miscarriages, mutagenic (DNA damage) abnormalities, and abnormal skeletons in animal studies. In addition, one metabolite (breakdown of the chemical into new chemical compounds during the metabolism process in the body) of imidacloprid appears to be far more toxic to mammals than the imidacloprid itself.

General risk factors in the use of flea and tick chemicals

Of course, not all cats and dogs exhibit immediately noticeable symptoms when dosed with a commercial spot-on flea product. Adult animals and those with healthy immune systems are less likely to show immediate signs compared to animals that are young, old, or suffering from chronic disease. Animals with repeated exposures to pesticides and/or with exposures from multiple sources such as a flea collar; other dips, sprays, dust, or flea bombs; yard pesticides; and house termite extermination, are more likely to react. The repetitive, cumulative and synergistic impacts of pesticides can take a heavy toll on animals.

Dr. Jerry Blondell, of the US EPA Office of Pesticides, has indicated clearly “not to use pesticides on the old, the sick, or the young.” While some of the literature for the spot-on products does discourage this usage, many cat and dog guardians and veterinarians overlook or disregard these written precautions.

Although the number of cats and dogs reported to react to these products may seem small, this does not suggest the overall impact is small. First, spot-on products are relatively new, and many problems are cumulative.

Second, reactivity to chemicals in a population is similar to other population statistics and is represented by a bell-shaped curve. In other words, at one end of the spectrum are sensitive individuals, and at the opposite end are resistant individuals; these groups are relatively small compared to the vast middle group, who show varying degrees of susceptibility – but who are all susceptible. Thus the sensitive group – cats and dogs who have displayed signs of toxicity – happen to be the sentinels for the younger, healthier ones who will eventually be affected; it’s just a matter of time.

But who would think the time span could be so short?  Through a Freedom of Information Act (FOIA) request for incident reports for both Advantage and Frontline products, thousands of reported adverse effects came flooding in. No longer are we looking at just laboratory test results, but finally the actual day-to-day effects from the use of the spot-on flea products.

Within one year of the introduction of Bayer’s product, Advantage, into the U.S., Bayer had received well over 600 incident reports, possibly close to 700.  Bayer’s reports to the US EPA were in poor condition and poorly documented, thus the EPA reviewers could only estimate the exact totals.

These reports alone included at least 70 deaths (17 dogs, 46 cats, 7 unspecified), 300 reports of skin irritation, 73 reports of central nervous system disturbances, including convulsions (seizures), 90 reports of lethargy, malaise, etc., and 92 reports of vomiting, diarrhea, or other gastrointestinal reactions.  Some animals had more than one reaction, but each animal was listed only one time in the above statistics.  Included with these were thousands of human incident reports listing adverse effects such as a non-asthmatic veterinarian who developed an asthmatic attack while treating a cat, women and men reporting extremity numbness, dizziness, and burns on their hands, and a shocking report of a previously healthy 12 year old boy who developed a grand mal seizure one hour after handling his Advantage-treated cat..

The New York  Attorney General’s statement that any decision to use pesticides is one made in ignorance, goes right to the heart of the matter.  There are no short cuts without a price attached.


  1. Eliot Spitzer, Attorney General of New York State, Environmental Protection Bureau, May The Secret Ingredients In Pesticides: Reducing the Risk
  2. United Nations Environment Prog., International Labor Org., and World Health Org., 1989 Allethrins: Allethrin, d-allethrin, bioallethrin, and s-bioallethrin.  Environmental Health Criteria 87. Geneva, Switzerland: WHO.
  3. Bayer web page
  4. Journal of Pesticide Reform/Fall 1997 Vol 17, No. 3 Table 1, Hazards of Flea Control Pesticides
  5. Dr. Virginia Dobozy, US EPA Pesticide Division, Health Effects-recommendations re:  Metabolism Study/Rat (85-1): MRID #429186-55 Fiprionil and Radioactive chemicals, June 28 1994
  6. IBID   
  7. PANNA fact sheet “chlorpyrifos
  8. Natural Resources Defense Council NRDC Poisons on Pets: Health Hazards from Flea and Tick Products, November 2001.
  9. NPTN fact sheet/Hayes, WJ (1982) Pesticides Studied In Man.  Baltimore:  Williams & Williams./Leahey, JP (Ed). (1985). The pyrethroid insecticides.  Philadelphia: Taylor & Francis Ltd. .
  10. Natural Resources Defense Council NRDC Poisons on Pets: Health Hazards from Flea and Tick Products, November 2001 –Adverse Effects on Pets from Select Products, pg 39
  11. EPA Press Advisory June 6 1997, Agreement Reached Between ZEPA And Chlorpyrifos Pesticide Registrants
  12. Bayer Web site
  13. US EPA Federal Register June 14, 2000  www.epa/gov/fedrgstr/EPA-PEST/2000/June/Day-14/p15034,htm
  14. Northwest Coalition Against Pesticides NCAP report Worst Kept Secrets: Toxic inert ingredients in pesticides
  15. NCAP et al Petition to require disclosure of inert ingredients on pesticide product Labels.
  16. NCAP report Worst Kept Secrets: Toxic inert ingredients in pesticides
  17. International Agency for Research on Cancer, IARC 1997 Monographs, Vols. 1-69, Lyon, France  
  18. The National Toxicology Program-Oregon State University Web Site
  19. Journal of Pesticide Reform, Caroline Cox, “Imidacloprid” fact sheet/Bayer Corp. Agriculture Div. 1996, Letter from T. McNamara, Biochemistry and pesticide registration manager to US EPA officer of Pesticide Project, 6(a)2 Document Processing Clerk, June 7/ Bayer Corp, Agricultural Div. 1996, Evaluation for topical use of imidacloprid (Advantage). Spot on  5 week old kittens, Shawnee Mission, KS., Aug 20.
  20. MSDS reference for Crop Protection Chemicals. 4th edition.  1992. New York, NY: Chemical and Pharmaceutical Press.
  21. US Dept. of Health and Human Services.  Public Health Service.
  22. Lawrence T Glickman et al., “Epidemiologic Study of Insecticide Exposures Obesity, and Risk of Bladder cancer in Household Dogs,” Journal of Toxicology and Environmental Health
  23. International Agency for Research on Cancer (IARC). IARC
  24. NCAP, Sandia. Marquardt, et al “Inert” Ingredients in Pesticides 1987-1997
  25. US EPA, Virginia Dobozy VMD,   June 28, 1994, M & B 46030 (fipronil)-Review of Toxicology Data Submitted by the Registrant
  26. NCAP, Caroline Cox/Soto, A M, KL Chung, and C Sonnenschein.  1994.  The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen –sensitive cells.  Environ. Health Perspect. 102:380-383.
  27. Our Daily Poisons, Leonard Wickenden, The Devin –Adair Company, NY 1956
  28. Cynthia Wilson, Chemical Exposure and Human Health: A Reference to 314 Chemicals with a guild to Symptoms and a Directory of Organizations, McFarland and Company
  29. Bayer Web site
  30. Merial Web site
  31. Journal of Pesticide Reform Vol 21, No 1, Spring 2001, Caroline Cox, “Imidacloprid”/Lagadic, Laurent, Ludovic Bernard, and Wolfgang Leicht.  1993.  Topical and oral activities of imidacloprid and cyfluthrin against susceptible laboratory strains of Heliothis virescens and Spodoptera Iittoralis. Pestic. Sci, 38(4):29-34.
  32. Journal of Pesticide Reform Vol 21, No 1, Spring 2001, Caroline Cox, “Imidacloprid”/US EPA Office of Pesticide Programs.  1996.  Imidacloprid.  Evaluation of products labeling data submitted and identification of outstanding toxicology data requirements.  Memo from MS Ottley, Health Effects Div., to P Jenkins, Registration Div Washington DC Mar 5
  33. Journal of Pesticide Reform Vol 21, No 1, Spring 2001, Caroline Cox, “Imidacloprid”/US EPA Office of Pesticide Programs. 1994. Pesticide fact sheet: Imidacloprid.  Washington DC Mar 18
  34. US EPA Prevention.  Pesticides and Toxic Substances.  1991.  Reregistration Eligibility Document (RED): Methoprene.  Washington DC Mar.
  35. PANNA web site for Imidacloprid
  36. Merial web site  “How Frontline Works” Nov 26 2001
  37. IBID
  38. IBID
  39. MRID #43577715
  40. Journal of Pesticide Reform Vol 21, No 1, Spring 2001, Caroline Cox, “Imidacloprid”/Holmes, P., LSR 92/RHA311/0464, M & B 46030 (Fipronil): Toxicity Study by Oral (Capsule) Administration to Beagle Dogs for 52 Weeks, November 16, 1992, Life Science Research Limited Suffolk, England by Rhone-Poulenc Ag Company
  41. Dr. Virginia Debozy, review of Fipronil Pet Products
  42. MSDS for diethylene glycol monoethyl ether
  43. ILO Encyclopedia of Occupational Health and Safety. Vols1 & 11  Geneva, Switzerland: 1983 975 **Peer Reviewed**)   Bayer’s flea product, Advantage, produced such symptoms as apathy, labored breathing, incoordination, emaciation, and convulsions, according to the “Imidacloprid”  fact sheet by the Northwest Coalition for Alternatives to Pesticides (NCAP).  
  44. US EPA Dobozy review of adverse effects “Frontline”.
  45. US EPA Fact sheet, “Imidacloprid
  46. US EPA Federal Register online
  47. Lawrence T. Glickman et al., “Epidemiologic Study of Insecticide Exposures Obesity, and Risk of Bladder Cancer in Household Dogs,” Journal of Toxicology and Environmental Health, 28:407-414
  48. MSDS-Frontline, Advantage
  49. ILO Encyclopedia of Occupational Health and Safety. Vols. 1 & 11 Geneva, Switzerland: 1983 975 **Peer Reviewed**)
  50. IARC.  Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.  Geneva:  WHO, International Agency for Research on Cancer, 1972-Present. (Multi volume work)., p.57-59 , 1987 **Peer Reviewed**
  51. EXTOXNET Fact sheet Permethrin,
  52. Journal of Pesticide Reform, Volume 21, Number 1 Spring 2001, Caroline Cox, “Imidacloprid”/US EPA Office of Pesticdes. 1994. Tox oneliners: Imidacloprid, Washington, DC Jan 3, p.1/Ref. #28. SeeSee attached Data Evaluation Report for MRID Nos. 422563-40 and 422563-39.
  53. Journal of Pesticide Reform, Vol 11, No.2, August 2001, Caroline Cox, “Imidacloprid”/Tomizawa, M. and JE Casida. 1999. Minor Structural Changes In Nicotinoid Insecticides Confer Differential Subtype Selectivity for Mammalian nicotinic acetylcholine receptors.  Bri. J Pharmacol 127:115-122
  54. Journal of Pesticide Reform Vol 14, No 4, Winter 1994, Caroline Cox, “Chlopyrifos”/RA Huff, JJ Corcoran, JK Anderson and MB Abou-Donia, Department of Pharmacology, Duke Univeristy Medical Center, Durham, North Carolina, Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP accumulation in rat striatum, Journal of Pharmacology and Experimental Therapeutics, Volume 269, Issue 1, pp. 329-335, 04/01/1994
  55. Journal of Pesticide Reform Vol 11, No 2, August 2001, Caroline Cox, “Imidacloprid”/Sander, J. and Buerkle, G. 1971. Induction of Malignant Tumors in Rats by Oral Administrations of 2-imidazolidinone and Nitrite. Z. Krebsforsch 75(4):301-304.(Abstract) / Szegedi, M 1983. Comparative mutagenic Investigation of the Decomposition Products of Alkylene bis(dithiocarbamate) fungicides and Neviram 80WP. Nehezvegyip.Kut.Intez.Kozl. 14:37-51. (Abstract)
  56. NPTN Pesticides in Indoor Air of Homes-General Fact Sheet/ EXTOXNET Oregon State University
  57. MSDS reference for Crop Protection Chemicals. 4th edition.  1992. New York, NY: Chemical and Pharmaceutical Press.
  58. US Dept. of Health and Human Services.  Public Health Service.
  59. Lawrence T. Glickman et al., “Epidemiologic Study of Insecticide Exposures Obesity, and Risk of Bladder Cancer in Household Dogs,” Journal of Toxicology and Environmental Health, 28:407-414
  60. Dr. Jerry Blondell, US EPA Pesticide Division, telephone communication, re:  Organophosphates/chlorpyrifos,  October 6 1998.
  61. EXTOXNET Fact sheet “Permethrin”
  62. US EPA Fipronil-Review of Incident Reports for Three Products– Review of Incidents from March 17, 1997-April 13 1998
  63. Review by Virginia Dobozy April 16 1997 “Fipronil-Review of Incident Reports for Three Products––Frontline Spray Treatment (65331-1), Top Spot for Cats (65331-2) and Top Spot for Dogs (65331-3).
  64. NCAP and the Journal of Pesticide Reform,  Godfrey, D.R. 1999. Dermatosis and Associated Systemic Signs in a Cat With Thymoma and Recently Treated With an Imidacloprid Preparation. J Small Animal Practice  40:333-337
  65. National Household Pesticides Usage Study,
  66. Telephone conversation re:  Organophosphates/chlorpyrifos,  October 6, 1998
  67. David Steinman, Living Healthy in a Toxic World/Briggs & Carson Council.  Basic Guide to Pesticides, p 211


Please note: The information provided here is intended to supplement the recommendations of your veterinarian. Do not disregard veterinary advice or delay treatment based on information on this site. Nothing can replace a complete history and physical examination performed by your veterinarian. -Dr. Jeff