Title: Assessing intermittent pesticide exposure from flea control collars containing the organophosphorus insecticide tetrachlorvinphos Davis MK, Boone JS, Moran JE, Tyler JW, Chambers JE Ref: J Expo Sci Environ Epidemiol, 18:564, 2008 : PubMed
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.
        
Title: Assessing transferable residues from intermittent exposure to flea control collars containing the organophosphate insecticide chlorpyrifos Chambers JE, Boone JS, Davis MK, Moran JE, Tyler JW Ref: J Expo Sci Environ Epidemiol, 17:656, 2007 : PubMed
Children can be exposed to pesticides from numerous residential sources such as carpet, house dust, toys and clothing from treated homes, and flea control remedies on pets. In the present studies, 48 pet dogs (24 in each of two studies) of different breeds and weights were treated with over-the-counter flea collars containing chlorpyrifos (CP), an organophosphorus insecticide. Transferable insecticide residues were quantified on cotton gloves used to rub the dogs for 5 min and on cotton tee shirts worn by a child (Study 2 only). First morning urine samples were also obtained from adults and children in both studies for metabolite (3,5,6-trichloro-2-pyridinol) quantification. Blood samples were obtained from treated dogs in Study 1 and plasma cholinesterase (ChE) activity was monitored. Transferable residues on gloves for all compounds were highest near the neck of the dogs and were lowest in areas most distant from the neck. Rubbing samples (over the collar) at two weeks post-collar application contained 447+/-57 microg CP/glove while samples from the fur of the back contained 8+/-2 microg CP/glove. In Study 2, cotton tee shirts worn by children at 15 days post-collar application for 4 h showed CP levels of 134+/-66 ng/g shirt. There were significant differences between adults and children in the levels of urinary metabolites with children generally having higher urinary levels of metabolites than adults (grand mean+/-SE; 11.6+/-1.1 and 7.9+/-0.74 ng/mg creatinine for children and adults, respectively, compared to 9.4+/-0.8 and 6.9+/-0.5 ng/mg creatinine before collar placement). Therefore, there was little evidence that the use of this flea collar contributed to enhanced CP exposure of either children or adults.
        
Title: Effects of topical phosmet on fur residue and cholinesterase activity of dogs Boone JS, Tyler JW, Davis MK, Chambers JE Ref: Toxicol Mech Methods, 16:275, 2006 : PubMed
Fleas, ticks, and mites are a major problem in many areas of the country for pet owners, and one treatment option involves the use of dips that contain pesticides. In the present study, dogs were dipped with a commercial phosmet (Imidan(R)) flea dip using the recommended guidelines for four consecutive treatments to determine the residues available for transfer to humans from the fur of the dogs. Twenty-four dogs of various breeds and weights were dipped, and each animal's fur was sampled with cotton gloves by petting for 5 minutes in a 10'' x 4'' area along the upper back before dipping and at 4 hours, and 1, 3, 7, and 14 days after dipping. Over the 4 dippings the 4-hour samples had a geometric mean of 2653 mug, and the 1-, 3-, 7-, and 14- day samples had geometric means of 877, 316, 84, and 20 mug, respectively. The samples ranged (in mug) from 80 to 16,794 at 4 hours, 44 to 7028 at 1 day, 1 to 4897 at 3 days, 1 to 2691 at 7 days, and 0.3 to 835 at 14 days. The residues removed by the petting did increase with the subsequent dips, but this was probably due to handler experience. The increase is not attributed to accumulation since there was less than 2% of transferable residue on the dog at 14 days post application. There was no significant inhibition of the plasma cholinesterase in the dogs over the study, suggesting that there was either a very low level of dermal absorption of phosmet or there was rapid detoxication (supported by EPA R 825170-01-0).
        
Title: Transferable Residues From Dog Fur and Plasma Cholinesterase Inhibition in Dogs Treated with a Flea Control Dip Containing Chlorpyrifos Boone JS, Tyler JW, Chambers JE Ref: Environmental Health Perspectives, 109:1109, 2001 : PubMed
We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a commercial, nonprescription chlorpyrifos flea dip for 4 consecutive treatments at 3-week intervals (nonshampoo protocol) and another 12 dogs were dipped with shampooing between dips (shampoo protocol). The samples collected at 4 hr and 7, 14, and 21 days after treatment in the nonshampoo protocol averaged 971, 157, 70, and 26 microg chlorpyrifos, respectively; in the shampoo protocol the samples averaged 459, 49, 15, and 10 microg, respectively. The highest single sample was about 7,000 microg collected at 4 hr. The pretreatment specific activities in the plasma of the dogs were about 75 nmol/min/mg protein for butyrylcholinesterase (BChE), and 9 nmol/min/mg protein for acetylcholinesterase (AChE). BChE was inhibited 50-75% throughout the study, and AChE was inhibited 11-18% in the nonshampoo protocol; inhibition was not as great in the shampoo protocol. There was no correlation (p
        
Title: Time course of inhibition of cholinesterase and aliesterase activities, and nonprotein sulfhydryl levels following exposure to organophosphorus insecticides in mosquitofish (Gambusia affinis) Boone JS, Chambers JE Ref: Fundamental & Applied Toxicology, 29:202, 1996 : PubMed
Cholinesterase (ChE) in brain and muscle was quickly inhibited during a 48-hr in vivo exposure to chlorpyrifos (0.1 ppm), parathion (0.15 ppm), and methyl parathion (8 ppm) in mosquitofish (Gambusia affinis). ChE remained inhibited during a 96-hr nonexposure period. Brain ChE reached peak inhibition by 12 hr after exposure to parathion and chlorpyrifos and by 4 hr after exposure to methyl parathion. All insecticides caused greater than 70% ChE inhibition by 4 hr in muscle. There was no recovery of ChE after 4 days of nonexposure in either brain or muscle. Hepatic aliesterases (AliE) were quickly and greatly inhibited (> 70% by 4 hr) after exposure to parathion and chlorpyrifos but not after exposure to methyl parathion. Exposure to methyl parathion required 24-36 hr to inhibit hepatic AliE to the same level as that following parathion and chlorpyrifos exposures at 4 hr. Exposure to all insecticides eventually resulted in greater than 80% inhibition of AliE. None of the test groups treated with insecticides showed any signs of significant recovery of AliE during the 4 days of nonexposure. Nonprotein sulfhydryl (NPSH) concentrations were lower than controls after 24 hr of exposure and 96 hr after recovery for all compounds. Exposure to methyl parathion lowered NPSH concentrations greater than the other compounds. Hepatic AliE appear capable of affording some protection of ChE from inhibition following parathion or chlorpyrifos exposures, but considerably less protection against methyl parathion.
        
Title: Role of detoxication pathways in acute toxicity levels of phosphorothionate insecticides in the rat Chambers JE, Ma T, Boone JS, Chambers HW Ref: Life Sciences, 54:1357, 1994 : PubMed
Phosphorothionate insecticides and their active oxon metabolites can be detoxified by a variety of hepatic mechanisms. Cytochrome P450-mediated dearylation activity was higher in males than in females. While dearylation was induced by phenobarbital in both sexes, it was induced by beta-naphthoflavone in females only. Detoxication of oxons in the presence of EDTA was inducible by phenobarbital, was higher in males than in females, and paralleled aliesterase activity. In vitro Ca(++)-dependent A-esterase-mediated hydrolysis of chlorpyrifos-oxon but not of paraoxon occurred at biologically relevant nM concentrations. This hydrolysis was also inducible by phenobarbital. Glutathione-mediated conjugation did not appear to be relevant to the disposition of the phosphorothionates studied here. Hepatic detoxication via dearylation, aliesterase phosphorylation and A-esterase-mediated hydrolysis (for some organophosphates) all appear to be relevant reactions in the attenuation of acute toxicity.