title: Concentrations of dimethylaniline and other metabolites in milk and tissues of dairy cows treated with lidocaine.
abstract: Lidocaine is a topical anaesthetic drug used in dairy cows for laparotomy (caesarean section, abomasal displacement). Because there are no registered drugs for this indication, it can be applied under the so-called Cascade rules (off-label use), with the restriction that the off-label withdrawal periods of 7 days for milk and 28 days for meat are taken into account. In animals, lidocaine is rapidly metabolised into various metabolites, one being 2,6-dimethylaniline (DMA) which is reported to possess carcinogenic and mutagenic properties and detected also in milk. To investigate whether the off-label withdrawal periods are long enough to exclude the presence of lidocaine and DMA, and potential other metabolites, in edible products, a study was performed with eight dairy cows treated with lidocaine by injection in the abdominal muscles. At various time points blood samples, milk and urine were collected. Four animals were slaughtered 3.5 h after treatment, the other four after 48.5 h. The injection site, meat, liver and kidney were analysed for levels of lidocaine, DMA, monoethylglycinexylidide (MEGX) and 3-OH-lidocaine. It was shown that DMA is an important metabolite in dairy cows and can be detected in both meat and milk. In addition, also MEGX, 3-OH-lidocaine and three other metabolites were identified and to some extent quantified. These metabolites were 4-OH-lidocaine, lidocaine-N-oxide and 4-hydroxy-DMA. The latter compound was the most important metabolite in urine. However, levels in milk and meat decreased rapidly after the application. Overall, it can be concluded that the off-label withdrawal times of 7 and 28 days for milk and meat, respectively, guarantee the absence of detectable levels of lidocaine and metabolites.
authors.affiliation: a RIKILT-Wageningen UR , Wageningen , the Netherlands.
authors.forename: Ron L A P
authors.initials: RL
authors.lastname: Hoogenboom
authors.forename: Tina
authors.initials: T
authors.lastname: Zuidema
authors.forename: Martien
authors.initials: M
authors.lastname: Essers
authors.forename: Ad M
authors.initials: AM
authors.lastname: van Vuuren
authors.forename: Piet G
authors.initials: PG
authors.lastname: van Wikselaar
authors.forename: Jan C H
authors.initials: JC
authors.lastname: van Eijkeren
authors.forename: Marcel J B
authors.initials: MJ
authors.lastname: Mengelers
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Zeilmaker
authors.forename: Astrid S
authors.initials: AS
authors.lastname: Bulder
mesh_terms: D000814:Aniline Compounds / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000032:analysis; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy*; D005260:Female; D005506:Food Contamination / Q000032:analysis*; D008012:Lidocaine / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D008460:Meat / Q000032:analysis; D008892:Milk / Q000737:chemistry*; D009153:Mutagens / Q000032:analysis; D013997:Time Factors
chemical_list: D000814:Aniline Compounds; D002273:Carcinogens; D009153:Mutagens; C007766:2,6-xylidine; D008012:Lidocaine
keywords: dairy cows; dimethylaniline; lidocaine; meat; milk