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 Spottreatments. 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 Advantagetell
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.
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
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