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Apr200

CONS U M ER ALERT
Are “Spot-On” Flea Killers Safe?
Absolutely not, says our author, despite what the commercials say. BY KATHLEEN DUDLEY
Tempting as it may be to simplistically
consider fleas as horrible insects, thebane of dogs everywhere, poisoningyour dog in a vain attempt to wipefleas out of existence doesn’t really make sense. Even though more than half abillion dollars annually are spent on prod-ucts that kill fleas in that vain pursuit.
everyone else in the household) perfectlymiserable. But it’s not as if using toxic flea-killing chemicals is the only way to controlfleas. When we attempt to get rid of ourdogs’ fleas by utilizing chemicals that are toxic to the brain and nervous system, that and that cause cancer, it’s sort of like burning the house down to get rid of ants – effective, describe effective, nontoxic methods of flea containing organophosphates (chlorpyrifos, vidual decisions on the acceptability of those control. No dogs (or any other members of malathion, diazinon), pyrethrins, synthetic exposures, a basic element in the mainte- nance and protection of our own health.” methods, and no dogs (or any other members cutting-edge solutions to our flea problems.
Spitzer adds, “The requirements for market- They were effective, but unfortunately, they ing a new product fall considerably short of contrast, dogs do get sick and die from the also caused disease and sometimes death.
providing safety for our animal and human toxic chemicals we will describe in this eventually cause enough human and animalinjuries that they are identified as hazards Active and inert ingredients
New products not safer
To fully understand the risks associated with All pesticides pose some degree of health any of these products, it is important to un- risk to humans and animals. Despite adver- called “spot-on” liquids that are applied derstand the various components in a flea tising claims to the contrary, both over-the- monthly to a dog’s skin – are being marketed product, or any chemical product that you counter and veterinarian-prescribed flea- killing topical treatments are pesticides that enter our dogs’ internal organs (livers, kid- alternatives to their predecessors, the fact products are made up of “active” and “inert” neys), move into their intestinal tracts, and is, they are simply newer. All the “active” ingredients; strangely, the actual definitions are eventually eliminated in their feces and ingredients in these spot-on preparations – of those phrases are very different from what they seem to connote. In the case of flea- other household animals who closely inter- methoprene, and pyriproxyfen – have been killing chemicals, the “active” ingredient linked to serious health effects in laboratory does, in fact, target and kill fleas – but some these chemicals can be affected by the tox- of the “inert” ingredients are poisons, too.
ins. What happens to the health of all ex- “The public must recognize that any de- While the word “inert” suggests benign posed individuals during this systemic ab- cision to use a pesticide, or to otherwise be sorption and filtration process varies from exposed to pesticides, is a decision made in minds of many consumers, legally, it simply animal to animal, but the laboratory and field ignorance,” says Eliot Spitzer, Attorney trial results clearly indicate toxicity on the registered “active” ingredient. This is important because most people assume that identity of the chemicals to which we are only the “active” ingredient in a chemical 18 | FEBRUARY 2002 Copyright 2002, Belvoir Publications, Inc.
cent of a test population – and to determine comforted by the idea that a product contains to disclose all the ingredients in their prod- the acute and chronic effects. Throughout only a minuscule amount of an “active” and following the test, subjects are killed in ingredient and up to 99.9 percent “inert” when the U.S. Congress passed the Federal order to study the specific system damage ingredients – a typical formula in many Insecticide, Fungicide, and Rodenticide Act (lungs, kidney, etc.). Acute disease tests, pesticide products. Actually, this makeup (FIFRA), allowing manufacturers confiden- such as nervous system and skin reactions, tiality on issues they claimed would other- can be performed over a relatively short time period. Most studies are conducted for 3-, petition. “Inert” ingredients, in other words, 13-, or 52-week intervals, and use exagger- agency that oversees the pesticide industry) became protected by industry as “trade se- requires a higher (if not high enough) stan- crets.” While protecting industry, this act dard of scrutiny for “active” ingredients; supersedes the public’s right to know to what “Because of the short period under which these must undergo a battery of tests to de- the studies are conducted, the health effects termine their toxicological profiles, be reg- resulting from the higher doses of the chemi- istered with the EPA, and be listed on the without full disclosure, we are unable to cals are relevant,” says Dr. Virginia Dobozy product inserts and packaging. In contrast, make educated decisions as to which chemi- of the EPA’s Pesticide Division. These ef- “inert” ingredients need not be listed on the product inserts and packaging and are sub- ject to much less testing than the “active” Laboratory studies
sponses; weight increase of the spleen, thy- ingredients; “inerts” are generally tested in Obviously, products undergo testing in or- mus, and adrenal glands; and/or atrophy of short-term studies for acute toxicity only.
der to qualify for EPA registration, and pre- The word “inert” implies chemicals that sumably, most of the overt dangers a prod- are somehow inactive. In actuality, many the chronic effects of the pesticides, are few “inert” ingredients used in pesticides are by comparison. Chronic disease such as can- as toxic, or more toxic, than the registered healthy, adult, genetically identical mam- cer, immune suppression, developmental or “active” ingredients. For example, naphtha- mals to test pesticides, and then extrapolate lene, one of the “inerts” in an imidacloprid health information regarding the safety of the product to domestic animals and human activity through inhalation (nasal cancers), beings. In the case of flea products, the labo- potential damage from continued use of one as well as anemia, liver damage, cataracts, ratory tests are performed on live mice, rats, and skin allergies. An unidentified “inert” products over a dog’s lifetime – is unknown.
ingredient in the flea product Advantage was Also unknown is the potential for synergistic implicated in the death of kittens who re- performed to establish the LD 50 – the oral ceived doses within laboratory tolerances.
dose at which the product would kill 50 per- exposures from their home and outdoorenvironments. Neither the cumulative northe synergistic effects of chemicals inproducts are required to be tested by the EPA Spot-On Pesticides and Their Ingredients
Advantage
Frontline Top Spot
(MSDS indicate inerts include some solvents) (MSDS indicates inerts include ethanol safety, but on a cost-benefit basis, balanc- Adams Spot-on Flea & Tick Control
against the economic gain to the manufac- (Note: Frontline Plus is essentially the same
turer and the end user of the product. But as Frontline Top Spot, but with the addition even if the pesticide manufacturers and the BioSpot Flea & Tick Control
Zodiac FleaTrol Spot On
Too good to be true
Today, spot-on flea preparations are consid- Defend EXspot Treatment
products, and sell swiftly in veterinary clin- ics and pet stores. Each of the makers of (800) 842-3532 or www.sgp.com/main.htmlActive ingred: these products claim that they are safe – safer than ever – and that only the targeted in-sects will be affected by the products’ neu- TO SUBSCRIBE: www.whole-dog-journal.com Copyright 2002, Belvoir Publications, Inc.
Adverse Effects of Ingredients Found in Spot-On Products
INGREDIENT
AFFECTED SYSTEM
LABORATORY ANIMAL HEALTH EFFECTS
Fipronil
Thyroid cancer (possible human carcinogen) Increased organ weights, altered thyroid hormones Loss of appetite, underactivity, convulsions, whining, barking, crying (vocalization), body twitches/tremors, overactivity, salivation, stiffened limbs, unsteady gait, incoordination, labored breathing Reduced fertility, decreased litter size and body weights in litters, fetus mortality Severe moist inflammation, ulcerations, skin sloughing, chemical burn, itching,hair loss at and beyond the application site Imidacloprid
Yet to be determined; evidence of thyroid lesions in dogs Liver, kidney, thyroid, heart, lungs, spleen, adrenal, brain, gonads; liver toxicity,increased organ weights, thyroid lesions, increased cholesterol levels in dogs Incoordination and labored breathing, muscle weakness including musclesnecessary for breathing Increased miscarriages and smaller offspring Methoprene
Headaches, eye and throat irritation, difficulty breathing, confusion, dizzinessand nausea in humans Permethrin
Liver and lung tumors (possible human carcinogen) Tremors, incoordination, elevated body temperature, increased aggressivebehavior, learning disruption Bone marrow changes in laboratory animals Pyriproxyfen
Butylhydroxanisole
Animal carcinogen (possible human carcinogen) Butyldydroxytoluene
Animal carcinogen (possible human carcinogen) Carbitol
Headache, depression, nausea, vomiting, diarrhea, abdominal and lumbar pain Pathological lesions in brain, lungs, liver menni; possibility of pulmonary edema,intravascular hemolysis and bone marrow depression Polyvinlpyrrolidone
Sources of the above information include reports from the Environmental Protection Agency; Occupational Safety & Health Administration, US Dept. of Labor; Extoxnet:Extension Toxicology Network; Journal of Pesticide Reform, Material Safety Data Sheets, Pesticide Action Network North America, and more. rotoxic impacts. The products are frequently pyrethroid insecticide) – all work by disrupt- tion, labored breathing, thyroid lesions, re- advertised as safe for small children and ing the nervous system of insects, killing by adults as well as puppies (over eight weeks) contact or ingestion. The fourth type con- and geriatric dogs. Do they sound too good tains insect growth regulators (IGR), which Fipronil was introduced in the United
don’t kill, but interrupt the flea’s life cycle.
States in 1996. It is a neurotoxin and sus- Imidacloprid is the first of its class of
general categories of insecticides. All have insecticides, and is relatively new on the cause liver toxicity, thyroid lesions (cancer), block; it was introduced in 1994. Labora- damage to the kidneys, increased cholesterol imidacloprid (a chloro-nicotinyl insecti- tory testing on mice, dogs, and rats, indi- levels, alterations in thyroid hormones, in- cide), fipronil (a phenylprazole insecticide), cates that this insecticide can be neurotoxic coordination, labored breathing, increased and permethrin (a synthetic broad spectrum to laboratory animals, causing incoordina- miscarriages, and smaller offspring.
20 | FEBRUARY 2002 Copyright 2002, Belvoir Publications, Inc.
could smell it on their breath in a matter of Learning to Read the Label
minutes following the application.” Blake stated that this indication of immediate ab- sorption did not tally with what he had been led to believe by reading Bayer’s literature.
He continues to question its safety for his Neurological health effects
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 rec-
ommend preventing their products from hav-
ing prolonged contact with the skin? And
why do they all state that skin sensations,
such as “numbness and tingling,” can oc-
cur? Schering-Plough’s MSDS makes an ad-
ditional statement about its Defend EXspot
through the skin and harmful following in- halation,” causing headaches, dizziness, and cent of the ingredients in Advantage, but itsMSDS does warn us to “use a respirator for companies’ literature describes in vague and organic vapors” in order to avoid “respira- tions, Dr. Virginia Dobozy of the EPA’s Pes- contradictory detail how the chemicals don’t tory tract irritation and other symptoms such ticide Division states that “this is a persis- go beyond the hair follicles and fat layers of tent chemical that has the potential for ner- nervous system exposure). Bayer’s promo- vous system and thyroid toxicity after long tional literature for Advantage, however, lished on Merial’s Web site for Frontline states that “studies prove that using 20-24 Permethrin, a synthetic broad spectrum
(“How Frontline Works”). In one place, it times the dosage on dogs and cats does not pyrethroid insecticide, is suspected to be an clearly states that fipronil (Frontline’s “ac- cause any internal or external side effects,” endocrine disrupter and a carcinogenic in- tive” ingredient) is absorbed into the skin and that “. . . switching to Advantage from secticide (causing lung cancer and liver tu- another flea control product poses virtually permethrin products have additional “ac- tive” ingredients in lesser percentages, and the United Kingdom, treated a four-year-old include methoprene, and pyriproxyfen (de- vantage Top Spot treatments. He reported Methoprene and pyriproxyfen are both
insect growth regulators (IGR), which limit clingy, and would not leave her guardian’s the development of juvenile fleas so they parts of the dog’s body – an illogical con- side, yet paced up and down all day, very cannot reproduce. Test results indicate that restlessly. These symptoms persisted for 48 methoprene causes enlarged livers and de- hours before a gradual return to her normal the results of a fipronil metabolism study, state.” The neurotoxic effects were clear to she reported that “significant amounts of ra- induced responses in laboratory animals that dio-labeled fipronil were found [not only] Dr. Blake also finds different results than give cause for alarm. While these new prod- in various organs and fat . . . [but they were the Bayer literature. “We are told that the ucts are suggested as safer than their prede- also] excreted in the urine and feces, and product affects only insects’ nervous sys- cessors, they indicate high levels of acute were present in other parts of the body . . .
tems, not mammals’. Several of my clients and chronic poisoning from short-term use.
Method of action
touched their mouths, their lips became im- Whether or not it is purposeful, manufac- close attention can witness evidence that mediately numb for several hours. So much turers of these spot-on flea products have these products are indeed systemically ab- for not having an effect on the nervous sys- sorbed. Dr. Stephen Blake, a San Diego vet- and animal guardians that these products are erinarian, relates a client’s experience: “We not absorbed into our dogs’ systems. The put Advantage on the backs of our dogs and and abdominal and lumbar pain are associ- TO SUBSCRIBE: www.whole-dog-journal.com Copyright 2002, Belvoir Publications, Inc.
ated with carbitol, one of the “inert” ingre- to animals that are young, old, or suffering dients in Frontline. According to the MSDS, from fipronil product studies, she found that from chronic disease. Animals with a height- carbitol induced these symptoms in labora- Frontline “does not adequately describe the ened sensitivity to chemicals or with expo- severe reactions” reported by veterinarians sures from multiple sources such as a flea Curiously, these potential side effects are – sloughing, “chemical burn” conditions, collar; other dips, sprays, dust, or flea not published in the literature accompany- ing the products, nor do many veterinarians anecdotal reports from veterinarians in the U.S. and the U.K. of dogs who were treated bathing the dogs. That’s strange, signs of neurological damage, such as de- the product remains effective after bathing.
pression, lethargy, convulsions, underactiv- The MSDS for Bayer’s Advantage tell fice of Pesticides, has indicated clearly “not ity, tremors, overactivity, stiffened limbs, us that “prolonged contact with the skin can to use pesticides on the old, the sick, or the cause defatting of the skin due to solvent young.” While some of the literature for the component in the products,” to “avoid skin spot-on products does discourage this us- Adverse skin effects
contact,” “to wear appropriate gloves when age, many dog guardians and veterinarians Topical skin irritation is listed on all the handling the product,” and to “wash off any overlook or disregard these written precau- MSDSs of the products reviewed in this ar- ticle; however, product literature inserts fail to emphasize the extreme nature of the prob- Chronic disease
to react to these products may seem small, lems. They all instruct the users that their Based upon toxicological studies, a dog suf- this does not suggest the overall impact is products are for “external use only,” and to fering from liver, kidney, thyroid, adrenal, small. First, spot-on products are relatively “avoid contact with the skin,” but only spleen, lung, brain or gonadal conditions new, and many problems are cumulative.
Merial’s product insert appears to suggest chronic diseases, with the potential for de- population is similar to other population sta- tistics and is represented by a bell-shaped preparations are used. Permethrin is linked curve. In other words, at one end of the spec- to malignant liver and lung tumors and au- trum are sensitive individuals, and at the opposite end are resistant individuals; these levels suppresses the immune system. Thy- groups are relatively small compared to the roid lesions have developed in laboratory studies in dogs during imidacloprid tests.
grees of susceptibility – but who are all sus- tions to Farnam’s flea product. In a letter to Further studies are necessary to understand ceptible. Thus the sensitive group – dogs the Farnam regarding a client who had used the possibilities of malignancy. Thyroid can- who have displayed signs of toxicity – hap- one of Farnam’s permethrin-based insecti- cer has been linked to fipronil, according to cides, Dr. Blanco stated, “All the dogs (20 the EPA. The data from the metabolism and healthier ones who will eventually be af- out of her 24 dogs treated with BioSpot ) chronic toxicity studies for fipronil indicate fected; it’s just a matter of time.
had pruritus (severe itching of the skin) with that “ . . . this is a persistent chemical and bleeding and cracking of the skin, various has the potential for nervous system and thy- Safe alternatives
degrees of erythema (intense redness of the roid toxicity after long-term exposure at low Integrated pest management (IPM) is a non- skin), many fluid vesicles (blisters), severe toxic approach used to eradicate any insect hair loss, and elephantiasis (thickening of In the Journal of Pesticide Reform, au- infestation. Simply, it is a way of thinking the skin) with chronic itching. Many also thor Caroline Cox cites studies that show about how to preserve the quality of life on showed severe mental depression, lethargy, thyroid sensitivity to imidacloprid can re- this planet and within the earth’s stratosphere sult in thyroid lesions, as well as increased – of understanding not only the damages of liver toxicity. All symptoms appeared within the pesticide to all species and the environ- (BioSpot) product, also a consistent time- mal skeletons in animal studies. In addition, quences of insect resistance to the constant frame for liver toxicity after absorption one metabolite (breakdown of the chemical parade of new, more sophisticated, and per- through the skin. . . To date, most of the dogs have dramatically improved but a few still IPM process was initially designed to safe- imidacloprid appears to be far more toxic guard all species, including the environment, to mammals than the imidacloprid itself.
of liver cancer within three months of this BioSpot application, which she says “could General risk factors
complete indoor and outdoor IPM treatment Of course, not all dogs exhibit immediately program for effective, non-poisonous flea of BioSpot.” Permethrin is indicated as a commercial spot-on flea product. Adult ani- liver enlargement and cancers in laboratory mals and those in the peak of health are less photgrapher, and lives in New Mexico. 22 | FEBRUARY 2002 Copyright 2002, Belvoir Publications, Inc.

Source: http://aspenbloompetcare.com/Are_Spot_On_Flea_Killers_Safe.pdf

Doi:10.1016/j.jbiotec.2008.07.1240

Abstracts / Journal of Biotechnology 136S (2008) S527–S540 (ACE) inhibitory activity, and the inhibitory pattern was found toRahman, M., Oomori, A., Uehara, T.T., 2008. Carbonic anhydrase in calcifiedendoskeleton: novel activity in bio-calcification in alcyonarian. Mar. Biotechnol. 50 values of compound 1 , compound 2 and compound 3 were 63.9 ␮M, 33.6 ␮M and 153.6 ␮M, respecti

cop-main.sites.medinfo.ufl.edu

Lobmeyer MT, Wang L, Zineh I, Turner ST, Gums JG , Chapman AB, Cooper-Dehoff RM, Beitelshees AL, Bailey KR, Boerwinkle E, Pepine CJ, and Johnson JA. Polymorphisms in Genes Coding for GRK2 and GRK5 and Response Differences in Antihypertensive-Treated Patients. Pharmacogenetics and Genomics ; 2011, Jan;21(1):42-9. Bovio J, Smith SM, Gums JG . Dabigatran Etexilate: A Novel Oral Thrombin Inhib

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