FARAD Digest

1 FARAD DigestResidue avoidance after topical applicationof veterinary drugs and parasiticidesRonald E. Baynes, DVM, MS; Arthur L. Craigmill, rhO; Jim E. Riviere, DVM, PhDThe use of topical veterinary drugs is of concern toveterinarians because of their over-the-counter avail-ability to laypersons. Extralabel use of topical drugs hasthe potential to cause violative residues. Parasiticides arethe most frequently used topical veterinary products (pre-scription OT over-the-counter). Other classes of topicaldrugs (eg, antibiotics and antiseptics) do not depend ondennal absorption to achieve therapeutic efficacy andare, therefore, unlikely to cause food animal the past 15 years, the Food Animal Residue Avoid-ance Databank ( FARAD ) has compiled a comprehensivedatabase1;2 of infonnation derived from published animalstudies (Appendix).

2 Some of these data provide the onlymeans to assess whether dermal absorption of drugs andpesticides will ~t in violative residues. It must be streSSedthat the Animal Medicinal Drug Use Clarification Act(AMDUCA) only allows extralabel use of approved organophosphates are approved for topical ap-plication in lactating dairy cattle. The prudent practition-er would administer drugs orally or select a different classof pesticides for topical use. Topical administtation ofthese moderately lipophilic pesticides may result in de-pot formation in the skin at the site of application as wellas prolonged residue depletion profiles. Although the pes-ticides are not registered for use in lactating cattle, FARADhas fielded calls pertaining to extralabel use in lactatinganimals.

3 The FARAD has, therefore, relied on a limiteddatabase from which to derive adequate withdrawal in-tervals for such pour-on products, such as Spotton (2~fenthion) and Triguvon (3% fenthion), are FDA approvedfor use in beef and nonlactating dairy cattle. Approvedmeat withdrawal times are 35 days after 1 treatment and45 days after 2 ~tments with the 3% formulation. Treat-ment with the 2~ formulation also requires a 45-daymeat withdrawal time. To avoid residues in milk, dairycattle should not be ~ted with the 3% formulation within28 days of initiation of lactation. Although < 2% of theabsorbed drug may be eliminated in milk, limited datasuggest that topical application of fenthion to lactatingcattle can result in substantial residues in milk within 24hours.

4 The FARAD discourages use of organophosphatesFrom the Food Animal Residue Avoidance Dat8bmk. Cuta-neous Pharmacology and Toxicology Center, Colle&e of VeterinaryMedicine, North Carolina State University, Raleigh, NC 27606(Baynes, Riviere), and the Environmental Toxicology Extension,College of AgricultUnl and Environmental ScieDCa, University ofCalifornia. Davis, CA 95616-8588 (Cralgmill).References for determinations are available on wrlttm lactating ruminants. However, if a fenthion producthas been used in a lactating animal, milk should be with-held for a minimum of 10 pour-on products, such as Warbex, areFDA approved for use in non lactating dairy catde mdbeef cattle to treat came grubs. The approved meatwithdrawal time is 35 days, and again, milk withdrawaltimes have not been established by the FDA.

5 Limiteddata suggest that for topical doses < 23 mg/kg (10 mgAb)of body weight, residue levels in milk are < ppmat 7 days and 0 ppm at 21 days. If a famphur producthas been used in a lactating animal, milk should bewithheld for a minimum of 10 products, such as CORAL. are EPA reg-istered for use as contact and pour-on insecticides innonlactating cattle. The meat withdrawal time is 10 days,and nonlactating dairy cattle should not be tteated < 14days before lactation begins. Data from several stUdiessuggest that < 6% of the applied dose of coumaphospour-on or spray fonnulations is absorbed; residues maybe detected in milk up to 14 days after treabnent. Inalmost all literatUre and case reports, coumaphos con-centrations were generally less than the milk and tissuetolerance levek within 7 to 14 days, despite the manydosage forms and formulations used to treat dairy a coumaphos product has been used in a lactating ani-mal, milk should be withheld for a minimum of 10 is EPA registered for use in ear tags forcatde and to treat screw worms (eg, Screw WanD & Earnck Spray) in calde, swine, sheep, and goats.

6 Ear tags areslow release devices with chlorpyrifos impregnated inthe plastic (polyvinyl chloride) and should be of mini-mum residue concern. Meat and milk withdrawal timesare 0 days for this pesticide. Data from several stUdiesdemonstrated that topical application may result in moreresidues in fat than in meat, although tissue residues weregenetally less than the tolerance level of 2 ppm for theentire experimental products, such as Purina Cattle Dust,are EPA registered for use in dairy and beef cattle. Meatand milk withdrawal times are 0 days. Most of the data inthe literature indicate small or negligible residue levels inmilk or body fat after topical exposure following variousdosage regimens and formulations.

7 Although severalmethoxychlor formulations contained mixtures ofbutoxypo1ypropylene glycol. diethyl-m-toluamide (DEET), pyre-thrlns, and/or piperonyl butoxide, milk residues againremained less than the tolerance products, such as Screw Worm Aerosol-L,are EPA ~gistered for use in beef cattle, sheep, swine,goats, and horses, and the meat withdrawal time is 0 daysfor these species. Lindane is not ~gistered for use indairy cattle, dairy barns, or milk rooms. Milk withdrawaltimes have not been established. Dennal absorption isslow and to a limited extent because of slow release fromthe str3tum corneum. Undane residue conccnttations ~considerably less than the tolerance leve1s in adipose tis-sue 30 days after pigs were sprayed with amounts rang-ing from the normal recommended dose ( g/pig) to16 times the normal dose ( Y/pig).

8 For goats and sheepdipped with lindane solution, higher residueswere found in sheep fat than in goat fat, but 2 weeks afterdipping, residue concentrations were less than the toler-ance leve1s. Because residues can be detected in meat andfat, there should be concern about milk residues if thisproduct is administered topically to lactating dairy from the literature suggest that pyrethrinsand, to some extent, pyrethroids (synthetic pyrethrins)are least likely to be absorbed through the skin of mostdomestic animals. For this reason, many of the mostcommonly used pyrethroids, such as permethrin, areEPA registered for use in most food animal speciesincluding lactating cattle and are, therefore, least likelyto be a residue products, such as Ectiban EC, are EPAregistered for use in laetating and beef cattle as well assmall ruminants and swine.

9 The meat withdrawal timeis 5 days in swine and 0 days in approved end Other Toplcel DrupThere are limited data regarding dennal absorptionof topical antibiotics in domestic animals; however, theiraction is local, because absorption into the bloods~Is not required for efficacy. Systemic exposure is minimal,making residue problems unlikely. Many of the topicalantibiotics used in veterinary medicine contain mixturesof 2 or more antibiotics or active ingredients. Nitrofun-zone is approved for topical use, but not parenteral ad-ministration, in food animals. Provided there is no oralingestion of nitrofurazones and tetracyclines, a meat ormilk withdrawal interval of 0 days is adequate for topicalexposure.

10 Copper sulfate, which often is used as a foot-bath to b'tat hairy warts in cattle, has a meat or milkwithdrawal interval of 0 (copper naphthenate), which is used totreat foot rot and ringworm, usually will not require amilk withdrawal interval as long as it is used topicallyand the chemical is not applied to the teats of lactatinganima has been used to treat hairy warts,and dennal absorption is unlikely to cause residues;thus, FARAD has recommended that a withdrawal in-terval is unnecessary. The FARAD does caution practi-tioners about use of formaldehyde, because it is con-sidered a probable human sulfoxide (DMSO) is rapidly abso'rbedthrough intact skin and may substantially alter absorp-tion characteristics of other simultaneously applied com-pounds.