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Assessing intermittent pesticide exposure from flea control collars containing the organophosphorus insecticide tetrachlorvinphos


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Fleas are a persistent problem for pets that require implementation of control measures. Consequently, pesticide use by homeowners for flea control is common and may increase pesticide exposure for adults and children. Fifty-five pet dogs (23 in study 1; 22 in study 2) of different breeds and weights were treated with over-the-counter flea collars containing tetrachlorvinphos (TCVP). During study 1, fur of treated dogs was monitored for transferable TCVP residues using cotton gloves to pet the dogs during 5-min rubbings post-collar application. Plasma cholinesterase (ChE) activity was also measured in treated dogs. Average amounts of TCVP transferred from the fur of the neck (rubbing over the collar) and from the back to gloves at 3 days post-collar application were 23,700+/-2100 and 260+/-50 microg/glove, respectively. No inhibition of plasma ChE was observed. During study 2, transferable TCVP residues to cotton gloves were monitored during 5-min rubbings post-collar application. Transferable residues were also monitored on cotton tee shirts worn by children and in the first morning urine samples obtained from adults and children. Average amounts of TCVP transferred to gloves at 5 days post-collar application from the neck (over the collar) and from the back were 22,400+/-2900 and 80+/-20 microg/glove, respectively. Tee shirts worn by children on days 7-11 contained 1.8+/-0.8 microg TCVP/g shirt. No significant differences were observed between adults and children in urinary 2,4,5-trichloromandelic acid (TCMA) levels; however, all TCMA residues (adults and children) were significantly greater than pretreatment concentrations (alpha=0.05). The lack of ChE inhibition in dogs and the low acute toxicity level of TCVP (rat oral LD(50) of 4-5 g/kg) strongly suggest that TCVP is rapidly detoxified and excreted and therefore poses a very low toxicological risk, despite these high residues.
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Assessing intermittent pesticide exposure from flea control collars
containing the organophosphorus insecticide tetrachlorvinphos
Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA
Fleas are a persistent problem for pets that require implementation of control measures. Consequently, pesticide use by homeowners for flea control is
common and may increase pesticide exposure for adults and children. Fifty-five pet dogs (23 in study 1; 22 in study 2) of different breeds and weights were
treated with over-the-counter flea collars containing tetrachlorvinphos (TCVP). During study 1, fur of treated dogs was monitored for transferable TCVP
residues using cotton gloves to pet the dogs during 5-min rubbings post-collar application. Plasma cholinesterase (ChE) activity was also measured in
treated dogs. Average amounts of TCVP transferred from the fur of the neck (rubbing over the collar) and from the back to gloves at 3 days post-collar
application were 23,700
2100 and 260
50 mg/glove, respectively. No inhibition of plasma ChE was observed. During study 2, transferable TCVP
residues to cotton gloves were monitored during 5-min rubbings post-collar application. Transferable residues were also monitored on cotton tee shirts
worn by children and in the first morning urine samples obtained from adults and children. Average amounts of TCVP transferred to gloves at 5 days
post-collar application from the neck (over the collar) and from the back were 22,400
2900 and 80
20 mg/glove, respectively. Tee shirts worn by
children on days 7–11 contained 1.8
0.8 mg TCVP/g shirt. No significant differences were observed between adults and children in urinary 2,4,5-
trichloromandelic acid (TCMA) levels; however, all TCMA residues (adults and children) were significantly greater than pretreatment concentrations
(a ¼ 0.05). The lack of ChE inhibition in dogs and the low acute toxicity level of TCVP (rat oral LD
of 4–5 g/kg) strongly suggest that TCVP is rapidly
detoxified and excreted and therefore poses a very low toxicological risk, despite these high residues.
Journal of Exposure Science and Environmental Epidemiology (2008) 18, 564–570; doi:10.1038/sj.jes.7500647; published online 2 January 2008
Keywords: tetrachlorvinphos, human pesticide exposure, flea control, transferable residues.
Pesticide exposures to infants and children from food, water,
and residential sources have been well documented (Woody,
1984; Zwiener and Ginsburg, 1988; Fenske et al., 1990;
Morgan et al., 2001; Castorina et al., 2003; Colt et al., 2003;
Rohrer et al., 2003; Hore et al., 2005; Boone et al., 2006;
Chambers et al., 2007). However, one area that does not
seem to have been appreciably explored is the possibility that
residues of insecticides remaining on pet fur from ea control
treatments could be a significant source of pesticide exposure
in children. Fleas are a continuous and persistent problem for
pets throughout the United States, especially in warmer
regions such as the South, where fleas are present most of the
year. To be efficacious, flea control insecticides must have
a residual effect on treated animals for several days, weeks,
or even longer. Collars impregnated with insecticides are
commonly used for flea control by homeowners, and may
serve as direct sources of exposure to children who pet or
hug treated animals. Thus, children are likely to have dermal
contact with these insecticides, a portion of which may
become an oral exposure because of their hand-to-mouth
behaviors. In warmer climates, an even greater risk of
exposure to these insecticides exists because children generally
wear less clothing and have less protection from contact with
treated animals.
Demographic studies indicate that more than 30% of all
US households own one or more pet dogs, a number that has
essentially been the same since 1987. This translates into an
average of approximately 1.6 dogs per dog-owning house-
hold or about 52 million dogs in the United States.
Furthermore, it has been shown that 59% of dog-owning
households have at least one child living in them (American
Veterinary Medical Association, 1997), which yields a
population of millions of children who could be in direct
contact with flea control insecticides from dogs alone.
Tetrachlorvinphos (2-chloro-1-(2,4,5-trichlorophenyl)vinyl
dimethyl phosphate (TCVP)) is one of a group of organo-
phosphorus (OP) insecticides that have been widely used for
Received 5 March 2007; revised 5 October 2007; accepted 5 November
2007; published online 2 January 2008
1. Address all correspondence to: Dr. J.E. Chambers, Center for
Environmental Health Sciences, College of Veterinary Medicine, Mississippi
State University, P.O. Box 6100, Mississippi State, MS 39762, USA.
Tel.: þ 662 325 1255. Fax: þ 662 325 1031.
Current address: United States Environmental Protection Agency,
Environmental Chemistry Branch, John C. Stennis Space Center,
Mississippi, USA.
Current address: Western University of Health Sciences, College of
Veterinary Medicine, Pomona, California, USA.
Journal of Exposure Science and Environmental Epidemiology (2008) 18, 564–570
2008 Nature Publishing Group All rights reserved 1559-0631/08/$30.00
flea control and numerous other agricultural and domestic
applications. TCVP (commonly referred to by the trade
names Rabon
and Gardona
) is a class III OP insecticide
with rat oral and rabbit dermal LD
s of 4–5 g/kg and 2.5 g/
kg, respectively. It has a half-life of 48 h (38% to 56% in
feces and 46% to 60% in urine), and its major metabolites
are trichlorophenylethanol (feces) and trichloromandelic acid
(urine) (USEPA, 1995).
All agricultural (crop) uses of TCVP were voluntarily
cancelled in 1987. Consequently, it is now mostly applied
dermally in poultry for the control of mites and flies and as
an oral feed-through larvicide for fly control in horses, cattle,
goats, and swine (USEPA, 1995; Berger et al., 2007). It is
also used for the control of nuisance and public health pests
(flies), as well as in the form of powder, aerosol, spray, or
shampoo for the dermal treatment of pets (USEPA, 1995).
Because TCVP is an organophosphate insecticide, its
primary mechanism of toxicity is the inhibition of the
nervous system enzyme, acetylcholinesterase (Ecobichon,
Because TCVP has been used in flea collars, the amount of
exposure to TCVP that could occur in children and adults
from the use of a TCVP-containing collar on a pet dog was
assessed. A long study (about 4 months) was conducted first
to determine the time course of transferable residue peak
and dissipation as assessed by transferable residues of TCVP
from the fur of dogs to white cotton gloves used to rub the
dogs. This was followed by a shorter study conducted over
3 weeks to include human biomonitoring of the TCVP
metabolite 2,4,5-trichloromandelic acid (TCMA) in urine of
children and adults. TCVP residues transferred to tee shirts
worn by children by contact with the dog were also quantified
to determine whether tee shirts might serve as a surrogate of
Study Design
These experiments were designed to determine the levels of
transferable TCVP residues to white cotton gloves from
rubbing the back of a dog at three locations: near the base of
the tail, at the neck with the collar removed, and at the neck
with the collar in place. Children’s potential exposure to and
absorption of TCVP were estimated by TCVP residues on tee
shirts worn by children for average 4-h periods at selected
times after pesticide application, as well as the metabolite
trichloromandelic acid (TCMA) levels in the first morning
urine sample, the morning following wearing the tee shirt.
Urinary TCMA was also monitored from an adult in the
household on the same sampling days.
Studies were conducted in Oktibbeha County, Mississippi
(USA), with volunteer households having pet dogs. Study 1
was a longer term study conducted over 112 days (September
to December 1998) because the collar used was recom-
mended by the manufacturer for 6-month use. Twenty-three
dogs from different households were used, and petting
samples from fur and dog plasma cholinesterase (ChE)
measurements were obtained. On the basis of the results from
the first study, which indicated that residues peaked and then
dropped substantially within 3 weeks of collar placement,
study 2 was performed over 21 days (September and October
2002) with 22 pet dogs from different households. Study 2
quantified residues of TCVP from petting and tee shirt
samples, and urinary metabolite TCMA in children and
In each of the two studies, flea collars (Hartz Control
Ultimate Flea Collar F 14.55% TCVP) were purchased
from a local department store. All collars were of the same
manufacturer’s lot number. Optima grade solvents (suitable
for gas chromatography) were obtained from Fisher
Scientific. The TCVP standard was obtained from Chem
Service (West Chester, PA, USA) and was greater than 99%
A commercial analytical chemistry laboratory (PTRL
West Inc., Hercules, CA, USA) was contracted to analyze
the human urine samples for the presence of TCMA, the
primary urinary metabolite of TCVP (USEPA, 1995). Since
TCMA cannot be readily prepared due to a lack of
commercial starting material, the structurally similar 2,3,6-
trichloromandelic acid analog was synthesized from 2,3,6-
trichlorobenzaldehyde and used as an internal standard. The
2,3,6-trichloromandelic acid was purified by re-crystallization
and was shown to have a purity of 488% by UV
spectrophotometric analysis (averaged result from two
wavelengths, 240 and 254 nm) and was characterized by
mass spectrometry with a purity of 97% (total ion current).
It is our assumption that the relative ion efficiency of the
internal standard (2,3,6-trichloromandelic acid) is similar to
the target analyte (TCMA).
The selection and care of pet dogs used in these studies were
in accordance with our earlier studies (Chambers et al.,
2007). Dogs were of a variety of breeds (including both short
and long hair breeds) and sizes (range 8–85 lb). All dogs were
healthy adults and were of both genders; no pregnant females
were used. All procedures were approved by the Mississippi
State University Animal Care and Use Committee.
Human Test Subjects
Participating families were volunteers who routinely used flea
control products on their pet dogs. One child and one adult
were selected from each participating family (study 2 only) as
previously described by Chambers et al. (2007). A copy of
the protocol was distributed to each participating household
Pesticide exposure from flea collars Davis et al.
Journal of Exposure Science and Environmental Epidemiology (2008) 18(6) 565
and informed consent was obtained from the adults. Children
were informed verbally of the procedures and oral or written
assent was obtained from them. The Institutional Review
Board for Research on Human Subjects at Mississippi State
University approved all sampling protocols and informed
consent forms.
Plasma Cholinesterase Assay
During study 1, plasma ChE activity was determined
spectrophotometrically from blood samples taken from each
dog at the same time as rubbing samples (Chambers et al.,
Rubbing Protocol
Dogs were petted in a marked 10 4inchareawithclean,
white, cotton gloves for a continuous 5-min period as
previously described (Boone et al., 2001). Samplers utilized
during both studies were students enrolled in the veterinary
medicine curriculum at the College of Veterinary Medicine,
Mississippi State University. Preparation of gloves and
sampling procedures described by Chambers et al. (2007)
were employed. Rubbing samples were obtained prior to
collar placement (day 0) and at 4 h, and 3, 7, 14, 28, 56, 84,
and 112 days post-collar application during study 1 and prior
to collar placement (0), and again at 5 and 12 days following
collar placement in study 2.
Tee Shirt Protocol
In study 2, child participants were supplied with a new,
laundered, white cotton tee shirt to wear on the day before
the treatment (pretreatment) and on each of days 7–11 post-
collar placement. Tee shirts were worn, stored, and prepared
for extraction as previously described (Chambers et al.,
Urine Sampling Protocol
During study 2, first morning urine samples (entire void)
were collected from the child wearing the tee shirt and from
one adult in the same household on the day prior to the
treatment and then again on each of days 8–12 post-collar
placement. Although the collection of 24-h urine samples
would be preferred due to the short half-life of TCMA
(USEPA, 1995), rst morning voids were more practical
to obtain because of the ages of the child participants (range
3–13). Furthermore, rst morning voids have been used in
many biological monitoring studies to evaluate the concen-
tration of environmental chemicals in human urine (Barr and
Angerer, 2006), and they have been shown to be the best
predictors of weighted-average daily metabolite concentra-
tions in the absence of a 24-h sample (Kissel et al., 2005).
Following collection, urine samples were brought to our
laboratories where a subsample consisting of 3 ml was
removed from each sample. Both the original samples and
the subsamples were placed in an upright freezer and held at
201C. The subsamples were shipped frozen to PTRL West
Inc. for analysis.
Determination of TCVP on Gloves and Tee Shirts
The gloves used to obtain rubbing samples were stored,
extracted, and analyzed as described earlier (Boone et al.,
2001). TCVP residues on tee shirts were determined using
the same procedures described for the gloves, except for a
methylene chloride preextraction step that was used to reduce
the loose cotton fiber content in the glove extracts. The
extractions and analyses used were modifications of the
methods of Zweig and Sherma (1977), Luke and Dahl
(1976), and EPA Test Methods 8141A, 8081, and 3540
(USEPA, 1993).
All samples were analyzed on an HP5890 gas chromato-
Separation of the analyte was achieved by using an RTX-5
Amine column (30 m 0.53 mm inside diameter/1.0 m lm
thickness Restek, Bellefonte, PA, USA). The oven tempera-
ture was ramped at a rate of 31C/min from 2051C to 2251C
and held for 5 min, followed by a second ramp of 51C/min to
a final temperature of 2901C. The ECD injector and detector
temperatures were set at 2901C and 3251C, respectively.
The limit of detection (LOD) was 2 p.p.b. and the limit of
quantification (LOQ) was 6 p.p.b. Various concentrations
(0.5–2500 mg) of TCVP were applied to different gloves and
tee shirts to determine recovery rates and extraction
parameters. The percent recovery obtained during these tests
ranged from 85% to 102%, with a mean of 95%.
Determination of TCMA in Urine
These analyses were conducted under contract to PTRL West
Inc. Urine samples were thawed at ambient room tempera-
ture, vortexed, and aliquoted (1.0 ml) to 1.8 ml glass auto-
sampler vials, and fortified with the 2,3,6-trichloromandelic
acid internal standard. Sufficient volume of concentrated
(12 N) hydrochloric acid (typically 0.1 ml) was then added to
each sample to achieve a final volume dilution of 1 N. Each
vial was then sealed with a PTFE/rubber-lined aluminum
crimp cap, vortexed to mix, and placed in a water bath
maintained at 801C for a period of 1 h, after which they were
allowed to cool to ambient temperature before being
Samples were analyzed by reverse-phase liquid chromato-
graphy mass spectroscopy using an Applied Biosystems/
MDS SCIEX API 3000 triple quadrupole mass spectrometer
and Analystt version 1.4 software. Analyses were performed
in the negative ionization mode using Turbo Ionsprayt
ionization. Two MS/MS transitions were monitored: 253-
209 and 255-211, which are associated with a loss of
from the corresponding molecular ions [M-H] at
Cl) and its associated
Cl at 255 AMU.Quantita-
tion was by integration of peak area for the single fragment
ion at m/z 209.
Pesticide exposure from flea collarsDavis et al.
566 Journal of Exposure Science and Environmental Epidemiology (2008) 18(6)
Separation of the two analytes (TCMA and 2,3,6-
trichloromandelic acid) from each other was achieved by
reverse-phase C-18 liquid chromatography. The target
analyte, TCMA, was identified by monitoring the two
MS/MS transitions previously mentioned and observing the
presence of a similar ion-intensity ratio of approximately 1:1
(for the fragment masses 209:211) as observed for the
internal standard. Because of an interfering, co-eluting
component detected in a large number of urine hydrolysates,
further identification of TCMA at the retention time of
13.9 min was conrmed by its anticipated longer retention
time relative to that of the 2,3,6-trichloromandelic acid
internal standard, which eluted at 12.4 min. The longer
retention of TCMA can be attributed to the differences in
polarity (TCMA is less polar than the 2,3,6-trichloroman-
delic standard).
A typical injection sequence for sample analysis involved
an initial acetonitrile solvent blank followed by a 20 ng/ml
internal standard quality control (prepared in acetonitrile)
and 10 experimental samples. This sequence was then
repeated until all samples were analyzed. The linear response
of the instrument was verified by sequential injections of
calibrants prepared in acetonitrile at nominal concentrations.
Quantitation of the target analyte (TCMA) was done by
comparing the peak areas of the internal standard (2,3,6-
trichloromandelic acid) and TCMA. LOD was 0.63 p.p.b.
and LOQ was 2 p.p.b. Samples that were below the LOQ
were assigned the value of the LOQ for the purpose of sample
analysis. Two percent of the adult samples were below the
LOQ, and 10% of the children’s samples were below the
LOQ. Except for pretreatment samples, none of the samples
were below the LOD. The accuracy of the method was
evaluated by examining the relative error of triplicate
concentrations for a selected analysis (family no. 110).
Relative error was calculated as (experimentally determined
concentrationtheoretical concentration) 100Ctheoretical
concentration. Magnitudes of relative errors were less than
17% at the lowest concentration, less than 12% at the mid-
level concentration, and less than 5% at the highest
concentration. The percent recoveries were in the range of
88.5% to 116.3%, with a mean of 102.1%.
With spot samples such as first morning voids, there is
variability in the volume of urine and the concentrations of
endogenous and exogenous chemicals from void to void that
must be considered. Urinary TCMA levels were adjusted
for urinary creatinine concentration for both adults and
children (Barr et al., 2005). Creatinine content of urine was
determined by colorimetric determination at 500 nm using a
creatinine kit (Creatinine-S Assay Kit; Diagnostic Chemicals
Limited, Oxford, CT, USA).
Statistical Analyses
Analysis of variance calculations for glove and tee shirt
residues were performed with the GLM procedure of the
System for Windows, Version 9.1, using the 0.05 level
of significance as described earlier (Chambers et al., 2007).
The glove and tee shirt data were also examined for
the presence of statistically significant correlations using
Spearman’s correlation coefficient. The calculation was
performed using the CORR procedure of the SAS System
for Windows, Version 9.1 (SAS Institute Inc., Cary, NC,
USA) at 0.05 level of significance.
Urinary TCMA data were statistically analyzed to
compare the amount of TCMA between adults and children.
The analyses were implemented in SAS System for Windows,
Version 9.1.3 using PROC MIXED with the REPEATED
statement and the autoregressive order one (AR 1)
covariance structure. The AR 1 was a covariance structure
with the desired property of correlations being larger for
nearby time than for far-apart times, which was a better fit in
this statistical model than the compound symmetric or
unstructured covariance.
No significant changes in dog plasma ChE activities from
pretreatment levels were observed except for one increase
of 10% at 84 days post-collar application; this statistical
difference was not viewed as biologically significant.
Significant increases in transferable TCVP residues were
observed from cotton gloves used to pet dogs compared to
pretreatment concentrations. In study 1, transferable residues
from all three sampling locations decreased throughout the
112 days following a peak at day 7 (Figure 1). Mean glove
residues for all sampling times were 14,300 mg/glove over the
collar, 4300 mg/glove on the neck with the collar removed,
and 130 mg/glove in the tail region. In study 2, residues
obtained over the collar and around the neck without the
collar in place decreased from 5 to 12 days post-collar
application, while pesticide residues obtained from the tail
TCVP ( µg/glove)
0 20 40 60 80 100 120
Figure 1. Mean transferable tetrachlorvinphos residues from 23
treated dogs to cotton gloves
SE (study 1).
Pesticide exposure from flea collars Davis et al.
Journal of Exposure Science and Environmental Epidemiology (2008) 18(6) 567
region remained fairly constant (Figure 2). Mean residues
(for all gloves) post-collar application were 19,000 mg/glove
over the collar, 8000 mg/glove on the neck with the collar
removed, and 80 mg/glove in the tail region.
Transferable TCVP residues peaked at 7 days post-collar
application (24,000
4000 mg/glove over the collar) in study
1 and then steadily declined until the end of the study (86%
decline). Similar trends were also observed in detectable
TCVP residues around the neck without the collar in place
and in the tail region where there were 94% and 71%
decreases, respectively. During study 2, the peak transferable
residues were collected over the collar at 5 days post-collar
application and were of a similar magnitude to those
observed in study 1. From 5 days post-collar application
until 12 days post-collar application, there was a 30% decline
in detectable TCVP residues obtained over the collar while
residues obtained from the tail region remained fairly
constant (81 mg/glove at 5 days and 82 mg/glove at 12 days
post-collar application).
The average amount of TCVP detected on children’s tee
shirts on sampling days 7–11 post-collar application was
0.8 mg/g shirt (mean
SE), with no significant differ-
ences among the sampling days (Figure 3). Transferable
TCVP residues were significantly greater than the mean
pretreatment residue of 0.03
0.006 mg/g shirt (mean
Urine samples obtained from children generally contained
more TCMA than that from the adults with significant
differences between the ages occurring on only one of the five
sampling days. Samples collected on day 11 from children
contained significantly greater TCMA residues than that
from adults. No significant differences in urinary TCMA
concentrations were observed among the adults or among
the children throughout the study. The ranges in urinary
TCMA concentrations were very large. For adults, the range
was 1.4–582 ng/ml urine, and for children the range was 2.1–
1558 ng/ml urine. As previously stated, the urinary TCMA
concentrations for adults and children were adjusted for
creatinine content. However, only unadjusted values are
reported here because there were no differences in the
outcome when urinary TCMA concentrations were adjusted
for creatinine content.
No significant correlations were present among transfer-
able TCVP tee shirt residues, the amount of time tee shirts
were worn, the amount of time spent with treated dogs,
and urinary TCMA concentrations. At the 0.05 level of
significance, mean Spearman’s correlation coefficients for all
variables examined were between 0.4 and 0.2, which
indicate the presence of very weak (low) associations among
the variables tested.
To reect the diversity among pet dogs and the diversity
within dog and human activity, we used different breeds and
sizes of dogs from 55 different families (23 in study 1 and 22
in study 2). Approximately half of the children and adults
were male and half were female. This variability should be
similar to that encountered with the normal use of flea
control collars among pet owners.
The results of the previous studies from our laboratory
using flea collars containing chlorpyrifos (CP) showed that
the greatest level of potential human exposure to CP from
flea collars, as assessed by the glove residues, occurred within
2 weeks of collar application and was greatest in the areas
on/near sites of application (Chambers et al., 2007). The
results obtained in the present studies yielded similar
patterns, with transferable TCVP residues to cotton gloves
highest over the collar and lowest in the tail region with a
peak at 1 week (Figures 1 and 2).
However, the overall magnitude of transferable residues
from the TCVP collars was much greater than was observed
TCVP (µg/Glove)
Figure 2. Mean transferable tetrachlorvinphos residues from 22
treated dogs to cotton gloves
SE (study 2).
TCVP (µg/g Shirt)
Treatment Samples
Pre-treatment Samples
Figure 3. Mean tetrachlorvinphos residues
SE on cotton tee shirts
worn by children at selected times post-application in study 2.
Pesticide exposure from flea collarsDavis et al.
568 Journal of Exposure Science and Environmental Epidemiology (2008) 18(6)
in our previous study with a CP-containing collar (Chambers
et al., 2007). The grand means
SEs (from both studies) for
samples taken from the collar were 16,600
1300 mg/glove
for TCVP and 370
60 mg/glove for CP. This very large
difference in magnitude, about 45-fold, could be attributed in
part to the concentration of the insecticides in the collars
(14.55% (4.8 g) active ingredient in the TCVP collar and 8%
(2.54 g) active ingredient in the CP collar). The differences
among the TCVP and CP studies may also be attributed to
different samplers, differences in dog fur composition from
one breed to another, and in all likelihood, different
formulation matrices between the two types of collars leading
to greater release of TCVP (for a 4-month collar) than CP
(for a 6 month collar).
Significant TCVP residues in cotton tee shirts indicate that
clothing could be a potential source of exposure for children.
All of the observed tee shirt residues were significantly greater
than pretreatment levels (which were essentially nil), but were
not significantly different from one treatment day to another.
The higher mean TCVP tee shirt residues on days 9 and 11
result from one very-high residue (17.9 and 17.3 mg/g shirt)
obtained from one tee shirt on each of these two sampling
days. When the aforementioned residues are excluded from
the analysis, the mean tee shirt residues
SE on days 9 and
11 are 1.2
0.5 and 0.800
0.5 mg/g shirt, respectively,
which are similar to the residues obtained from the tee shirts
of other children on those days. We believe these higher
residues are related to the amount of time these two children
spent in direct contact with their pet dogs on those two
Children generally had greater urinary concentrations of
TCMA than adults, similar to the higher levels of the CP
metabolite trichloropyridinol observed in our earlier study
(Chambers et al., 2007). Maximum TCMA concentrations
were observed on post-treatment day 11 (199
74 ng/ml
urine) for children and on post-treatment day 12 for adults
38 ng/ml urine). TCMA residues in all samples were
significantly greater than pretreatment levels (which were
essentially nil), indicating that some TCVP is absorbed by
both adults and children. The grand means for adults and
children’s urinary TCMA concentrations were 65
22 and
56 ng/ml urine, respectively. At the 0.05 significance
level, these concentrations represent 6- and 16-fold increases
above pretreatment levels, respectively. Even though we
expected significant correlations among time spent with dogs,
transferable TCVP residues, and urinary TCMA concentra-
tions, there were no such correlations present at the 0.05 level
of significance. Although disappointing, the lack of signifi-
cant correlations is consistent with other studies utilizing
passive dosimeters and biomonitoring of urinary metabolites
(Honeycutt et al., 2000; Geer et al., 2004; Fenske and Day,
2005). Pretreatment values for TCVP on gloves or tee shirts
and for TCMA in urine were essentially zero, reflecting the
very limited usages of TCVP, and, therefore, little wide-
spread environmental contamination. These results are in
contrast to CP that was present prior to collar placement,
reflecting the wider usage of CP.
In summary, significantly greater residues of TCVP were
detected in both glove and tee shirt samples obtained post-
collar application than in pretreatment samples. Further-
more, TCMA, a urinary metabolite of TCVP, was also
detected in urine samples from both adults and children,
indicating that some of the TCVP may be absorbed.
However, since there are very few published data quantifying
human exposures to TCVP, these results should be
interpreted with caution because the toxicological significance
of these residues is presently unknown. The lack of ChE
inhibition in dogs and the low acute toxicity level of TCVP
(rat oral LD
of 4–5 g/kg) strongly suggest that TCVP is
rapidly detoxified and excreted and therefore poses a very low
toxicological risk, despite these high residues. It should also
be noted that these data may not be representative of other
flea control formulations, as indicated by the differences in
magnitude of residues between this study and our previous
study on CP. However, caution should be observed when
applying flea control insecticides to pets, especially those in
direct contact with children, and especially for the rst few
days after applying the collar.
This research was supported by grants from the US
Environmental Protection Agency’s Science to Achieve
Results (STAR) grant program (Grant nos. R825170 and
R828017). Although the research described herein has been
funded wholly or in part by the US Environmental
Protection Agency STAR program, it has not been subjected
to any governmental review and therefore does not reflect the
views of the agency. No official endorsements should be
inferred. We thank Ms. Nicole Holield, Ms. Susan
Waldrop, and Mr. Collin Zumwalt for residue analyses, as
well as creatinine and cholinesterase assays, Drs. Carolyn
Boyle and Sumalee Givaruangwawat for statistical advice,
and Dr. Louis Ruzo and Curtis Hatton (PTRL West Inc.)
for the analysis of urine for TCMA. This research was
also supported by the Mississippi Agriculture and
Forestry Experiment Station (MAFES) and the College
of Veterinary Medicine, Mississippi State University.
This article is MAFES publication number J11104 and the
Center of Environmental Health Sciences publication
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... The use of veterinary flea products has been linked to both environmental as well as human exposure and effects (Cochran et al., 2015;Davis et al., 2008;Muilerman and Manthingh, n.d.;Perkins et al., 2021a;Teerlink et al., 2017). These anti-flea and tick products may end up in the indoor and outdoor environment, through direct and indirect pathways such as urine, shed hair, bathing, swimming and rain events. ...
... Dog hairs and urine have been used as an indicator for organic pesticide exposure and as a sentinels for human exposure, as pets and humans often share the same habitat in which secondary transfer can occur (Forster et al., 2014;González-Gómez et al., 2018). This secondary transfer has been demonstrated for a range of AIs from flea and tick products (Bigelow Dyk and RI, 2012;Boone et al., 2001;Chambers et al., 2007;Cochran et al., 2015;Craig et al., 2008;Davis et al., 2008;Jennings et al., 2002). Secondary transfer between dog hair used as a nesting material was also proposed to explain juvenile mortality in the great tit (Parus major) (Guldemond et al., 2019); in this study, 26 pesticides were found in the birds, including fipronil and imidacloprid. ...
... The hypothesis of secondary transfer by direct dog-to-dog contact is supported by several studies showing a significant transfer of administered chemicals from dogs onto cotton gloves and other items. This route is, for example, further highlighted by a study of Davis et al. (2008), which indicated that dogs treated with tetrachlorvinphos collars showed a significant transfer of the chemical onto cotton gloves used to pet the dog and cotton tee shirts worn by children who were in contact with the dog. Residues decreased over time after treatment, but were still measurable at the end of the study at 112 days. ...
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Worldwide, the number of pet dogs increases yearly, and as a result so does the use of veterinary medicines for flea and tick control. We investigated the potential transfer of veterinary flea products from dogs to the environment in a ‘proof of principle’ experiment. For this purpose, samples of hair, urine, and water after swimming were investigated. Nine dogs were recruited for this study, eight of which had been recently treated with an ectoparasiticide product. Hair and urine samples were tested for afoxalaner, fluralaner, fipronil and imidacloprid. Interestingly, contamination with ectoparasiticides was frequently demonstrated in samples from dogs untreated with these particular substances, suggesting widespread secondary transfer. In addition, hair retrieved from a bird's nest contained fipronil, fluralaner and imidacloprid, indicating a potential pathway for the exposure of juvenile birds. Three of the dogs also participated in a swimming experiment. One had been treated with oral fluralaner, whilst the remaining two had received other compounds not included in our study. However, in all three dogs, both fluralaner and imidacloprid were detected in hair samples. Fluralaner concentrations in the swimming water exceeded Dutch water quality standards, indicating a potential risk to the aquatic environment. Imidacloprid levels increased after each swimming dog, but did not breach Dutch water quality standard levels. These findings all call for improvements in the current risk assessment and management for veterinary medicines, by including companion animals and their exposure pathways into ecosystems.
... The test set was compiled of organophosphates, carbamates and structurally non-classified pesticides. Regarding organophosphates, chlorpyrifos [37], DDVP [14], fenitrothion [38], azinphosmethyl [39], naled (dibrom) [40], TCVP [41], parathion [39], methyl parathion [42], diazinon [43], phosmet [14], azamethiphos [44], and terbufos [45], respectively, are used as insecticides. Moreover, glyphosate is a broad-spectrum systemic herbicide and crop desiccant [46], malathion is mostly used for mosquito eradication [47], parathion is used as an acaricide. ...
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Commercially available pesticides were examined as Mus musculus and Homo sapiens acetylcholinesterase (mAChE and hAChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards, molecular docking and dynamics SB studies were performed on either mAChE or hAChE, to predict the listed pesticides’ binding modes. Calculated energies of global minima (Eglob_min) and free energies of binding (∆Gbinding) were correlated with the pesticides’ acute toxicities (i.e., the LD50 values) against mice, as well to generate the model that could predict the LD50s against humans. Although for most of the pesticides the low Eglob_min correlates with the high acute toxicity, it is the ∆Gbinding that conditions the LD50 values for all the evaluated pesticides. Derived pLD50 = f(∆Gbinding) mAChE model may predict the pLD50 against hAChE, too. The hAChE inhibition by atrazine, propazine, and simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM) DFT mechanistic and concentration-dependent kinetic studies, enriching the knowledge for design of less toxic pesticides.
... Urine biomonitoring revealed that human exposure to fipronil is low. Residues of tetrachlorvinphos (TCVP) on gloves used to rub dogs with collars containing TCVP were 16,600 μg/glove and 1.8 μg/g of tee shirts worn by children contacting the dogs [442]. The lack of cholinesterase inhibition in dogs and the low acute toxicity of TCVP suggest that it is rapidly detoxified and excreted. ...
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The cat flea Ctenocephalides felis felis (Bouché) is the most important ectoparasite of domestic cats and dogs worldwide. It has been two decades since the last comprehensive review concerning the biology and ecology of C. f. felis and its management. Since then there have been major advances in our understanding of the diseases associated with C. f. felis and their implications for humans and their pets. Two rickettsial diseases, flea-borne spotted fever and murine typhus, have been identified in domestic animal populations and cat fleas. Cat fleas are the primary vector of Bartonella henselae (cat scratch fever) with the spread of the bacteria when flea feces are scratched in to bites or wounds. Flea allergic dermatitis (FAD) common in dogs and cats has been successfully treated and tapeworm infestations prevented with a number of new products being used to control fleas. There has been a continuous development of new products with novel chemistries that have focused on increased convenience and the control of fleas and other arthropod ectoparasites. The possibility of feral animals serving as potential reservoirs for flea infestations has taken on additional importance because of the lack of effective environmental controls in recent years. Physiological insecticide resistance in C. f. felis continues to be of concern, especially because pyrethroid resistance now appears to be more widespread. In spite of their broad use since 1994, there is little evidence that resistance has developed to many of the on-animal or oral treatments such as fipronil, imidacloprid or lufenuron. Reports of the perceived lack of performance of some of the new on-animal therapies have been attributed to compliance issues and their misuse. Consequentially, there is a continuing need for consumer awareness of products registered for cats and dogs and their safety.
To understand the environmental spread of both organophosphate pesticides and glyphosate, it is important to consider how the use of many has grown. While not universally true, since initially marketed, the volume of use for most has grown dramatically. At the same time, understanding the extent of use is challenging. Changes in product patents, proprietary trade information, regulatory restrictions, and other factors make it difficult to fully estimate how much is used, especially on a global basis. The following chapter examines these issues. It also considers the most currently available data for the state of California, which, in the US, has the most detailed information.
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Pesticide treatment dramatically reduces crop loss and enhances agricultural productivity, promoting global food security and economic growth. However, owing to high accrual and persistent tendency, pesticides could create significant ecological consequences when used often. Lately, the perspective has transitioned to implementing biological material, environmentally sustainable, and economical strategies via bioremediation approaches to eradicate pesticides contaminations. Microalgae were regarded as a prominent option for the detoxification of such hazardous contaminants. Sustainable application and remediation strategies of pesticides pollutants in the agriculture system by microalgae from the past studies, and recent advancements were integrated into this review. Bibliometric strategies to enhance the research advancements in pesticide bioremediation by microalgae between 2010 and 2020 were implemented through critical comparative analysis of documents from Scopus and PubMed databases. As a result, this study identified a growing annual research trend from 1994 to 2020 (nScopus > nPubMed). Global production of pesticide remediation by microalgae demonstrated significant contributions from India (23.8%) and China (16.7%). The author’s keyword clustering was visualized using bibliometric software (VOSviewer), which revealed the strongest network formed by “microalgae”, “bioremediation”, “biodegradation”, “cyanobacteria”, “wastewater”, and “pesticide” as significant to the research topic. Hence, this bibliometric review will facilitate the future roadmap for many scholars and authors who were drawing attention to the burgeoning research on bioremediation of pesticides to counteract environmental impacts while maintaining food sustainability.
Two organophosphate pesticides—glyphosate and tetrachlorvinphos—have been announced as carcinogens to humans by various authorities, including the European Chemical Agency and the Environmental Protection Agency. We aimed to investigate molecular mechanisms associated with carcinogenicity and to examine changes in global m ⁵ C DNA methylation and cytotoxic potential in A549 lung epithelial cells in response to glyphosate and tetrachlorvinphos, and differential gene expression of m ⁵ C DNA methyltransferase genes in Sprague Dawley rats to Roundup (commercial formulation of glyphosate). Global m ⁵ C level significantly increased after 1500 μM glyphosate exposure for 24 h. We determined that exposure to tetrachlorvinphos did not significantly increase the m ⁵ C level in A549 cells for 24 h. Additionally, we did not observe significant DNA methylation alteration for both pesticides after 12 h exposure. In the animal study, we observed that DNA methyltransferase genes (DNMT3b and DNMT3a) showed significantly higher expression in Roundup-exposed rats than the control group in the liver and kidney. We also observed that a significant cytotoxic effect was determined after the treatment of the cells with higher concentrations of glyphosate and tetrachlorvinphos. Our results revealed that DNA methylation could be modified by exposure to glyphosate and that exposure to Roundup was associated with the differential expression level of m ⁵ C DNA methylation methyltransferase. Finally, exposure to both pesticides increased cytotoxicity.
Tetrachlorvinphos is an organophosphate that is classified as a carcinogen in humans by several authorities. Due to very limited data regarding the genotoxic potential, we aimed to comprehensively investigate in vitro genotoxic potential of tetrachlorvinphos. We performed our study by applying the cytokinesis-block micronucleus cytome and sister chromatid exchange (SCE) assays to human peripheral blood lymphocytes. We evaluated micronucleus (MN) and SCE frequencies and cytokinesis-block proliferation index in both exposed and non-exposed lymphocytes. We also calculated the chromosomal instability level in response to exposure by combining the results of MN and SCE. We found that MN frequency did not increase with exposure to tetrachlorvinphos (0–50 µg/ml). In contrast, we observed that SCE frequencies significantly increased with exposure to ≥5 µg/ml tetrachlorvinphos. Furthermore, exposure to tetrachlorvinphos at concentrations of 50 µg/ml induced a significant increase in chromosomal instability level ( p < 0.05). Cytokinesis-block proliferation index level did not significantly decrease in response to tetrachlorvinphos exposure. Our findings reveal that tetrachlorvinphos resulted in different DNA damages that were measured by two assays. Furthermore, our findings suggested that exposure to tetrachlorvinphos increased chromosomal instability that is a hallmark of many malignancies. We conclude that although tetrachlorvinphos does not significantly increase the MN level, the significant increase of both SCE and CIN frequencies indicates the genotoxic potential of tetrachlorvinphos in human peripheral lymphocytes. Additionally, tetrachlorvinphos is not cytotoxic in the range of tested concentrations.
Purpose of review: Consumer products are often overlooked as sources of children's exposures to toxic chemicals. Various regulatory bodies have developed lists of chemicals of concern that can be found in products contacted by children. However, this information has not been summarized for health practitioners. This review organizes such chemicals and products into four categories, with the antibacterial agent triclosan used to illustrate the potential risks to children from a common ingredient in consumer products. Recent findings: Biomonitoring, house dust, indoor air, and product testing document children's exposures to a wide variety of chemicals. An increasing number of epidemiology studies have shown associations between these exposures and health effects in children. Triclosan is an example of a chemical contained in high contact products (e.g., soaps, lotions, and toothpaste) not necessarily designed for children. Triclosan exposure in children has been associated with increased responsiveness to airway allergens, with it also capable of endocrine disruption. However, the utility and necessity of this chemical in consumer products has not been demonstrated in most cases. Summary: Triclosan and the other examples provided show that a changing marketplace with little regulatory oversight of chemical uses can lead to unanticipated exposures and potential health risks to children.
This chapter appraises the prevention, control, and/or eradication of pests such as fleas from pet animals. In the case of companion animals, or domestic pets, various external parasites, internal parasites, and viruses require pest control products, such as insecticides, for prevention and/or treatment. Some of the common infectious agents, such as roundworms and hookworms, are zoonotic. These products can be in various forms, such as mousses, spot-ons, flea collars, oral tablets, powders, and spray mists. While there are many relatively safe insecticide products available for use on pets, caution still must be observed and products should always be used strictly according to their label directions. The key areas of research for pet care pesticide products include Pet care product use/usage data collected in conjunction with human-pet interaction videography and/ordiary surveys; Comparative evaluation of transferable residue methods (e.g., human hands, gloved human hands, gloved mannequin hands) and associated modeling of the data as a function of contact level, contact duration, and time post-treatment; and evaluation of predictive algorithms with comparisons to the results of human exposure and biomonitoring studies. The ideal methods for estimating exposure involve chemical-specific passive dosimetry that measures dermal and inhalation exposure or biomonitoring. Understanding animal safety and potential human health risks associated with these products is a very important ongoing process that will continue to be used to balance risks and benefits.
This chapter focuses on the use of pesticides in domestic food and pet species. Pesticides are frequently topically applied or orally administered to animals to control harmful insects and parasites or used in their environment to control a variety of pests. The rural setting of food-producing and livestock-rearing operations results in exposure of domestic animals to the wide array of agricultural chemicals currently in use. In addition, wildlife species are often exposed accidentally or maliciously to pesticides, especially those used in animal and plant agriculture. Pesticide exposures can be minimal or can be sufficiently great to produce clinical signs and result in acute poisoning, delayed toxicity, or residues that affect public safety through contamination of the food chain. The likelihood of intoxication depends on a variety of physiological, behavioral, and environmental factors. Fortunately, the emergence of less toxic pesticides for veterinary use has resulted in less frequent acute animal intoxications. Chronic exposure to pesticides applied to lawns has been hypothesized as a cause of bladder cancer in certain dog breeds, although this remains controversial. The diagnosis of pesticide intoxication requires careful antemortem and postmortem investigation. Treatment of intoxicated animals involves early decontamination, symptomatic and supportive care, and, in some cases, antidote administration.
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Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the US Environmental Protection Agency (EPA) has the authority to regulate the use of pesticides to prevent unreas-onable adverse human health effects associated with pesticide exposure. Accordingly, the EPA requires pesticide registrants to perform studies evaluating the potential for pesticide handler exposure. Data from five such studies that included exposure measurements based on both external measurements and biological monitoring were used to examine methods of assessment, routes and determinants of exposure and dose to the pesticide chlorpyrifos. Eighty workers across four job classes were included: mixer/loaders (M/L, n = 24), mixer/loader/applicators (M/ L/A, n = 37), applicators (A, n = 9) and re-entry scouts (RS, n = 10). Results showed that doses were highly variable and differed by job class (P < 0.05) with median total (inhalation and dermal combined) exposure-derived absorbed doses (EDAD tot) of 129, 88, 85 and 45 mg/application for A, M/L/A, M/L and RS, respectively. Doses derived from the measurement of 3,5,6-trichloro-2-pyridinol (3,5,6-TCP) in urine were similar in magnitude but differed in rank with median values of 275, 189, 122 and 97 mg/application for A, M/L, RS, and M/L/A, respectively. The relative contribution of dermal to inhalation exposure was examined by their ratio. The median ratios of exposure-derived absorbed dermal dose (EDAD derm) (assuming 3% absorption) to exposure-derived absorbed inhalation dose (EDAD inh) (assuming 100% absorption) across job classes were 1.7, 1.5, 0.44 and 0.18 for RS, M/L, A and M/L/A, respectively, with an overall median of 0.6. For 34 of 77 workers (44%), this ratio exceeded 1.0, indicating the significance of the dermal exposure pathway. Different dermal absorption factor (DAF) assumptions were examined by comparing EDAD tot to the biomarker-derived absorbed dose (BDAD) as a ratio where EDAD tot was calculated assuming a DAF of 1, 3 and 10%. Median ratios of 0.45, 0.71 and 1.28, respectively, were determined suggesting the DAF is within the range of 3–10%. A simple linear regression of urinary 3,5,6-TCP against EDAD tot indicates a positive association explain-ing 29% of the variability in the 3,5,6-TCP derived estimate of dose. A multiple linear regression model including the variables EDAD derm , EDAD inh and application type explained 46% of the variability (R 2 = 0.46) in the urinary dose estimate. EDAD derm was marginally significant (P = 0.066) while EDAD inh was not (P = 0.57). The EDAD derm regression coefficient (0.0007) exceeded the coefficient for EDAD inh (0.00002) by a factor of 35. This study demonstrates the value of the pesticide registrant database for the purpose of evaluating pesticide worker exposure. It highlights the significance of the dermal exposure pathway and identifies the need for methods and research to close the gap between external and internal exposure measures.
IntroductionPesticide CategoriesPesticide HandlersStudy Design ConsiderationsProtection of Human SubjectsPesticide Exposure Monitoring Methods Validation of Passive DosimetryUse of Pharmacokinetic DataExposure Mitigation MeasuresExposure Studies Supporting Registration DecisionsConclusions and RecommendationsAcknowledgementsReferences