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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Overview of the drug classes
  5. Conclusions
  6. Acknowledgements
  7. References
  8. Appendix

Goetting, V., Lee, K. A., Tell, L. A. Pharmacokinetics of veterinary drugs in laying hens and residues in eggs: a review of the literature. J. vet. Pharmacol. Therap.34, 521–556.

Poultry treated with pharmaceutical products can produce eggs contaminated with drug residues. Such residues could pose a risk to consumer health. The following is a review of the information available in the literature regarding drug pharmacokinetics in laying hens, and the deposition of drugs into eggs of poultry species, primarily chickens. The available data suggest that, when administered to laying hens, a wide variety of drugs leave detectable residues in eggs laid days to weeks after the cessation of treatment.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Overview of the drug classes
  5. Conclusions
  6. Acknowledgements
  7. References
  8. Appendix

In poultry, antibiotics and antiparasitics are used extensively for disease prevention and treatment. In the United States, antibiotics are also used for growth promotion, although this type of use has been prohibited in the European Union since 2006 (Donoghue, 2003; Castanon, 2007; Companyo et al., 2009). Edible tissues containing veterinary drug residues can pose risks to human health, including direct toxic effects, allergic reactions and increased bacterial resistance to common antibiotics (Botsoglou & Fletouris, 2001; Donoghue, 2003; Companyo et al., 2009).

Drug residues in chicken eggs are of concern because relatively few drugs are labelled for laying hens, although several medications are approved for other production classes of poultry (Hofacre, 2006; Castanon, 2007). Drug residues in eggs may arise when laying hens are mistakenly given medicated feed, when feed is contaminated at the mill during mixing, or when drugs are given off-label (Kennedy et al., 2000; Donoghue, 2003). While a chicken lays an egg roughly every 24 h, each egg takes several days to develop in vivo, and some egg components are in existence months before the fully developed and shelled egg containing them is laid (Etches, 1996; Whittow, 2000). Because of the protracted nature of egg development, many weeks may be required following treatment or exposure before eggs are free of drug residues.

It should be noted that some drugs included in this review are prohibited from use in some or all food animals in the US and/or the EU. In the US, extra-label use of fluoroquinolones is prohibited in food animals, and any use of these drugs in a manner not explicitly approved is illegal. If an animal is mistakenly or intentionally treated with a drug that is prohibited from extra-label drug use, then the exposed animal(s) should not enter the food chain unless permission is granted from the proper authorities. In both the US and EU, other drugs, including chloramphenicol, the nitroimidazoles, and nitrofurans, are completely prohibited from use in food animals (Davis et al., 2009; EMEA, 2009). A summary of drugs approved in the US for game bird species has been published (Needham et al., 2007), and a recent update on drugs prohibited from extra-label drug use in the US is available (Davis et al., 2009). EU approval statuses and maximum residue limits for veterinary drugs used in food-producing animals are described in the European Commission Regulation 37/2010 (European Commission, 2009).

Of the three main egg components (yolk, albumen, and shell), the yolk has the longest development time. Precursors to yolk lipoproteins are produced in the liver and transported through circulation to the yolk follicles in the ovary. In an actively laying hen, several follicles at varying developmental stages reside simultaneously in the ovary. Before an egg is laid, the yolk undergoes a stage of rapid growth, in which it increases in size exponentially over 10 days (Etches, 1996). Drugs that deposit in the yolk will rapidly accumulate during this time and can be present in successive eggs for 10 or more days following treatment. Following yolk maturation, the albumen or ‘egg white’ is laid down over a period of 2–3 h (Whittow, 2000) and can also serve as a residue accumulation site. The egg shell is added after albumen proteins are deposited and diluted with water (Etches, 1996). The egg development process is similar across species of poultry and game birds, although the rates of development vary (Whittow, 2000). A detailed diagram of a chicken egg is shown in Fig. 1.

image

Figure 1.  Detailed illustration of the components of a developing avian egg.

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Many drugs deposit preferentially in the yolk or albumen, depending on the drug’s physicochemical properties. Some characteristics that effect the distribution of residues are the drug’s tendency to bind to plasma proteins, hydrophobicity or hydrophilicity, and the ability to move through different tissue types (Martinez, 1998). However, a drug’s kinetic properties cannot always be predicted from its chemical properties (Donoghue, 2005). This review presents a compilation of studies found scattered throughout the literature that address the kinetics of veterinary drugs in laying hens.

Overview of the drug classes

  1. Top of page
  2. Abstract
  3. Introduction
  4. Overview of the drug classes
  5. Conclusions
  6. Acknowledgements
  7. References
  8. Appendix

Antimicrobials

Aminocyclitols.  Aminocyclitols (e.g. spectinomycin and apramycin) are antimicrobial compounds produced by Streptomyces and Micromonospora spp. (Botsoglou & Fletouris, 2001). Aminocyclitols are effective against gram-negative and some gram-positive bacteria, but not anaerobic bacteria, because their mechanism of action relies on bacteria’s oxygen transport system (Dowling, 2006). In poultry, administration is most commonly oral, via the feed or water. A limited number of studies in chickens demonstrate that following oral administration there is little or no absorption of the drugs from the gastrointestinal (GI) tract, and therefore when given orally, aminocyclitols are likely to be effective primarily against GI infections (Bennett et al., 2001). The main excretory pathway following oral administration in mammals is the faeces (Brown & Riviere, 1991). Probably because of poor GI absorption, spectinomycin residues are not found in eggs following oral administration (Table 1). In contrast, orally administered apramycin is found in the egg albumen for several days following treatment (Romvary et al., 1991) (Table 1). This difference between the two aminocyclitols could be attributable to differences in serum protein binding affinity: in vitro, chicken serum protein binding of apramycin is 26% (Afifi & Ramadan, 1997), compared with 5–6% for spectinomycin (El-Sayed et al., 1995). In mammals, absorbed apramycin can concentrate in the kidney and persist unchanged for prolonged periods (Botsoglou & Fletouris, 2001).

Table 1.   Persistence of residues of aminoglycoside medications in chicken eggs following treatment of laying hens
Aminoglycosides & aminocyclitolsApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; spectinomycin was given with lincomycin. The doses here refer to the amount of spectinomycin only; a veterinary gentamicin formulation containing 50 mg/mL was used; §apramycin in the form of apramycin sulphate was used; kanamycin sulphate was added to feed. The concentrations per kg feed indicate the amount of active compound added.

DihydrostreptomycinEU: not approved USA: not approvedNoneBioassayY: 3; A: 0.3 mg/kgNS*Water1 g/L (100 mg/kg bw*)13–185WE: 0Roudaut (1989b)
IM*100 mg/kg bw13–181Y: 9; A: 2; WE: >9
SpectinomycinEU: not approved USA: approvedUSA: 0 mg/kgBioassay12 mg/kgNSWater0.5 g/L (50 mg/kg bw)13–185WE: 0Roudaut (1989b)
Bioassay2 mg/kgNSFeed110 mg/kg feedNS7WE: 0Cuerpo and Livingston (1994)
165 mg/kg feedNS7WE: 0
220 mg/kg feedNS7WE: 0
GentamicinEU: not approved USA: not approvedNoneHPLC*0.01 mg/kgNSSC*10 mg/kg bw7.51Y: 7; A: 3; WE: 7Filazi et al. (2005)
25 mg/kg bw7.51Y: 10; A: 4; WE: 10
50 mg/kg bw7.51Y: 12; A: 5; WE: 12
IM10 mg/kg bw7.51Y: 7; A: 3; WE: 7
25 mg/kg bw7.51Y: 10; A: 4; WE: 10
NeomycinEU: approved USA: not approvedEU: 500 μg/kgBioassayY: 9.6 mg/kg; A: 0.15 mg/kg; WE: 1.2 mg/kgNSWater0.25 g/L (25 mg/kg bw)13–185WE: 0Roudaut (1989b)
ApramycinEU: not approved USA: not approvedNoneBioassayNSY: 0.138; A: 0.049 mg/kgWater20 mg/kg bw§NS5Y: 0; A: >10Romvary et al. (1991)
KanamycinEU: not approved USA: not approvedNoneBioassay0.5 mg/kgNSFeed20 mg/kg feed107Y: 0; A: 0Yoshida et al. (1976)
1000 mg/kg feed107Y: 0; A: 0
4000 mg/kg feed107Y: >0; A: 0
8000 mg/kg feed107Y: >0; A: 0
16 000 mg/kg feed107Y: >7; A: 0

Aminoglycosides.  The aminoglycosides (e.g. streptomycin, neomycin, gentamicin) are antimicrobial compounds produced by Streptomyces and Micromonospora spp. (Botsoglou & Fletouris, 2001). Like aminocyclitols, aminoglyosides are effective against gram-negative and some gram-positive bacteria, but not anaerobic bacteria (Dowling, 2006), and are not absorbed well from the GI tract (Bennett et al., 2001). The main excretory pathway following oral administration in mammals is the faeces (Brown & Riviere, 1991). Based on the physical properties of aminoglycosides (cationic, with a high degree of polarity), birds most likely also eliminate orally administered aminoglycosides in the faeces, although data specific to birds are lacking. Probably because of the poor GI absorption of aminoglycosides, it is rare to find aminoglycoside residues in eggs following oral administration (Table 1).

When aminoglycosides are given systemically, the main route of elimination in mammals is via the kidneys (Botsoglou & Fletouris, 2001). In mammals and birds, systemic administration of aminoglycosides is complicated by their nephrotoxicity (Botsoglou & Fletouris, 2001). There are no avian-specific data on the pharmacokinetics of systemic aminoglycosides, but as birds and mammals both exhibit aminoglycoside-induced nephrotoxicity, it is likely that elimination occurs via the renal pathway in birds as it does in mammals (Frazier et al., 1995). Systemically administered aminoglycosides are much more bioavailable than when given orally (Abu-Basha et al., 2007a); therefore, residues are more likely to be found in eggs. When administered to laying hens via IM or SC routes, both gentamicin and dihydrostreptomycin were deposited in egg yolk and albumen, with residues persisting for longer periods in the yolk (Roudaut, 1989b; Filazi et al., 2005) (Table 1).

Amphenicols.  The amphenicols (e.g. chloramphenicol, thiamphenicol, florfenicol) are broad-spectrum antimicrobials, effective against Rickettisia and Chlamydophila spp., anaerobic and gram-positive aerobic bacteria, and enteric bacteria (Bishop, 2001). The original source of chloramphenicol was the bacterium Streptomyces venezualae. Chloramphenicol is now produced synthetically, and thiamphenicol is a synthetic derivative (Papich & Riviere, 2001). As a result of its potential to cause bone marrow suppression in humans, most countries have restricted or banned the use of chloramphenicol in food animals (Dowling, 2006).

In poultry, amphenicols are given orally in feed or water (Botsoglou & Fletouris, 2001). Following oral administration to chickens, absorption is rapid but incomplete (Anadon et al., 1994a), and the drug is rapidly and thoroughly distributed throughout the body (Anadon et al., 1994a, 2008b). Excretion pathways vary by drug. In most mammalian species studied, chloramphenicol is processed by the liver and excreted in urine and bile (Bennett et al., 2001). The pathways of chloramphenicol elimination have not been described for avian species. However, in chickens, thiamphenicol is eliminated via both the biliary and renal systems (Francis, 1997), and florfenicol is partly metabolized to florfenicol amine, with significant residues of both parent drug and metabolite found in the liver and kidney (Anadon et al., 2008b). Rate of elimination is affected by route of administration; chloramphenicol is eliminated more quickly following IV administration compared with oral administration (Anadon et al., 1994a). The limited residue studies of amphenicols performed in laying hens demonstrate that residues are found in both yolk and albumen for several days following oral administration (Table 2). When treatment was repeated for several days, residues persisted longer than a week (Samouris et al., 1993; Akhtar et al., 1996b).

Table 2.   Amphenicol residues in chicken eggs following treatment of laying hens
AmphenicolsApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; chloramphenicol given in a commercial formulation, Kamycetin® from K-vet Laboratories, Hespeler, ON, Canada; chloramphenicol was given with an equal concentration (0.04%) furazolidone; §groups of young birds were dosed at the ages of 13, 15, 17, 19, 21 and 40 weeks, respectively; ¶14C-radiolabelled chloramphenicol was used; **thiamphenicol given as thiamphenicol base in the glycinate form.

ChloramphenicolEU: prohibited USA: prohibitedNoneColorimetric0.1 mg/kgNS*Water40 mg/LNS5Y: >5; A: 4Sisodia and Dunlop (1972)
RIA*1 μg/kg5 μg/kg500 mg/L38WE: >17Scherk and Agthe (1986)
1000 mg/L36WE: >19
RIA0.3 μg/kg0.5 μg/kg60 mg/kg bw*1010WE: >72Schwarzer and Dorn (1987)
HPLC*10 μg/kgNSFeed800 mg/kg feedNS1Y: 4; A: 9Samouris et al. (1993)
HPLCNS0.02 mg/kg400 mg/kg feed7.514WE: 8Petz (1984)
HPLC10 μg/kgNS200 mg/kg feedNS5Y: 6; A: 2Samouris et al. (1998)
500 mg/kg feedNS5Y: 8; A: 3
800 mg/kg feedNS5Y: 9; A: 3
1000 mg/kg feedNS5Y: 9; A: 4
RIA0.3 μg/kg0.5 μg/kg35 mg/kg bw§3.257WE: 0Schwarzer and Dorn (1987)
35 mg/kg bw§3.757WE: 0
35 mg/kg bw§4.257WE: 0
35 mg/kg bw§4.757WE: 23
35 mg/kg bw§5.257WE: 23
35 mg/kg bw§107WE: 73
LSC*NSNSGavage0.5 mgNS5Y: >7; A: 3Akhtar et al. (1996b)
5.0 mgNS5Y: >7; A: 3
ThiamphenicolEU: not approved USA: not approvedNoneHPLCNS10 μg/kgOral (capsule)40 mg/kg bw**61Y: 10; A: 2Giorgi et al. (2000)
40 mg/kg bw**65Y: 8; A: 1

Beta-lactams.  Beta-lactams are grouped by a shared structural feature, a beta-lactam ring containing one nitrogen and three carbon atoms (Prescott, 2006). The beta-lactam class encompasses some of the most commonly used antimicrobials, both in human and veterinary medicine, including the penicillins. The broad-spectrum penicillins are effective against many gram-negative and gram-positive bacteria, including anaerobic bacteria (Dorrestein et al., 1984; Vaden & Riviere, 2001). While penicillins are considered less toxic than many other antimicrobials, the potential for allergic reactions in humans makes penicillin residues in food of particular concern (Dewdney et al., 1991). In poultry, penicillins are given orally for preventative and therapeutic purposes (Prescott, 2006). The effectiveness of orally administered penicillins is reduced by their susceptibility to hydrolysis in the GI tract (Prescott, 2006). In domestic mammals, penicillins are widely distributed in extracellular fluids following absorption (Prescott, 2006), have short half-lives and are metabolized primarily by the kidneys (Vaden & Riviere, 2001). In birds, the available data suggest that the hepatic, rather than renal, excretion pathway may predominate (Dorrestein et al., 1984; Frazier et al., 1995).

Ampicillin, the only penicillin for which egg residue data exists, is relatively stable in gastric acid and well absorbed compared with many other penicillins (Botsoglou & Fletouris, 2001). Nonetheless, bioavailability of ampicillin is higher when injected IM than when given orally (Ziv et al., 1979; Frazier et al., 1995). The greater persistence of ampicillin residues in eggs when administered IM compared with the oral route (Roudaut et al., 1987b) (Table 3) could be tied to this difference in bioavailability.

Table 3.   Beta-lactam residues in chicken eggs following treatment of laying hens
Beta-lactamsApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Time until residues no longer detected (days from last treatment)Source
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; ampicillin given as ampicillin sodium; two injections of 10 mg/kg were given 6 h apart; §n = 1.

AmpicillinEU: not approved USA: not approvedNoneBioassayY: 0.005, A: 0.008 mg/kgNS*Water100 mg/L115WE: 0Roudaut et al. (1987b)
200 mg/L11.55Y: 2; A: 0
1500 mg/L185Y: 3; A: 0; WE: 3
IM*20 mg/kg bw*121Y: 5; A: 2
BioassayY: 2.1 μg/kgNS40 mg/kg bw12.51Y: 7Donoghue et al. (1997)
40 mg/kg bw12.52Y: 8
40 mg/kg bw12.53Y: 9
CephalexinEU: not approved USA: not approvedNoneELISA*60 μg/kgNSFeed20 mg/henNS7Y: >21; A: 0§Kitagawa et al. (1988)

Cephalosporins, like penicillins, are a sub-group of beta-lactams derived from fungi (Cephalosporium acremonium) (Vaden & Riviere, 2001). First-generation cephalosporins such as cephalexin are primarily effective against Staphylococcus spp., Streptococcus spp., Escherichia coli, Proteus mirabilis, and Klebsiella spp. Following oral administration of cephalexin to chickens, the drug is widely distributed and found in high concentrations in the bile, suggesting hepatic metabolism (Kitagawa et al., 1988). Cephalexin appears to preferentially deposit in egg yolk, and residues can be long lasting (Kitagawa et al., 1988).

Macrolides.  The macrolide antibiotics (e.g. erythromycin, tylosin, spiramycin) are a structurally similar group of primarily bacteriostatic compounds. Most drugs in this class were isolated from soil bacteria of the genus Streptomyces (Papich & Riviere, 2001). Macrolides are effective against Mycoplasma spp. and gram-positive organisms such as Streptococcus spp. and Staphylococcus spp., but are only slightly effective against gram-negative bacteria (Botsoglou & Fletouris, 2001). In laying hens, the most common route of administration is oral, although one instance of IM dosing is included in Table 4 (Roudaut & Moretain, 1990), and bioavailability appears to be high (Goudah et al., 2004; Abu-Basha et al., 2007b). In birds as in mammals, available data suggest that macrolides are widely distributed and penetrate well into tissues and cells following absorption (Anadon & Reeve-Johnson, 1999; Botsoglou & Fletouris, 2001; Keles et al., 2001; Goudah et al., 2004; Fricke et al., 2008). In mammals, macrolides are metabolized by the liver and excreted in bile. Some of the metabolized drug is re-absorbed in the GI tract, but most is excreted in faeces, and secondarily in urine (Giguere, 2006). In birds, tylosin is excreted primarily in faeces, but a large portion is also excreted in urine (van Leeuwen, 1991; Lewicki et al., 2008). Persistent macrolide residues can be deposited in eggs following oral (via feed or water) or parenteral administration to laying hens. Most macrolides are found in egg yolk for several days after residues become undetectable in the albumen (Table 4), as might be expected owing to macrolides’ lipophilicity (Anadon & Reeve-Johnson, 1999) and the longer developmental timeline of yolk compared with albumen. Although spiramycin appears to be an exception, persisting in egg albumen longer than in egg yolk, this pattern is likely attributable to the higher sensitivity of the assay used to detect the drug in albumen (Roudaut & Moretain, 1990).

Table 4.   Macrolide residues in eggs following treatment of laying hens
MacrolidesApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; tylosin given as tylosin tartrate; tylosin given as tylosin phosphate; §a commercial preparation of 25% tylosin (25 g tylosin phosphate/100 g) was mixed in the feed; spiramycin given as spiramycin adipate; **spiramycin given as spiramycin embonate; ††aqueous solution of spiramycin base (50 g/kg).

TylosinEU: approved USA: approved200 μg/kg (EU & USA)LC/MS*0.5 μg/kg1 μg/kgWater500 mg/L55WE: 8Hamscher et al. (2006)
BioassayY: 0.2, A: 0.15 mg/kgNS*500 mg/L7–165Y: 0; A: 0Roudaut and Moretain (1990)
BioassayY: 0.5, A: 0.45 mg/kgNS500 mg/LNS7Y: 6; A: 3Yoshimura et al. (1978)
LSC*0.02 mg/kgNS529 mg/LNS3WE: 6Marth et al. (2001)
BioassayY: 0.2, A: 0.15 mg/kgNS1000 mg/L7–165Y: 6; A: 1Roudaut and Moretain (1990)
BioassayNSNS530 mg/L7.57WE: 0McReynolds et al. (2000)
530 mg/L7.510WE: 0
Bioassay0.15 mg/kgNS500 mg/L51WE: 3Iritani et al. (1976)
500 mg/L53WE: 4
500 mg/L55WE: 5
Bioassay0.4 mg/kgNSFeed20 mg/kg feed107WE: 0Yoshida et al. (1973a)
BioassayY: 0.2, A: 0.15 mg/kgNS400 mg/kg feed7–167Y: 0; A: 0Roudaut and Moretain (1990)
Bioassay0.4 mg/kgNS500 mg/kg feed107WE: 0Yoshida et al. (1973a)
LC/MS0.5 μg/kg1 μg/kg1500 mg/kg feed§55WE: 8Hamscher et al. (2006)
Bioassay0.4 mg/kgNS8000 mg/kg feed107Y: 6; A: 2Yoshida et al. (1973a)
SpiramycinEU: not approved USA: not approvedNoneBioassayY: 0.33, A: 0.1 mg/kgNSWater400 mg/L7–165Y: 9; A: 10Roudaut and Moretain (1990)
BioassayY: 0.5, A: 0.4 mg/kgNS500 mg/LNS7Y: 20; A: 14Yoshimura et al. (1978)
Bioassay0.45 mg/kgNSFeed20 mg/kg feed107Y: 0; A: 1; WE: 1Yoshida et al. (1971)
50 mg/kg feed107WE: 2
100 mg/kg feed107WE: 2
200 mg/kg feed107WE: 1
BioassayY: 0.33, A: 0.1 mg/kgNS400 mg/kg feed**7–167Y: 7; A: 15Roudaut and Moretain (1990)
Bioassay0.45 mg/kgNS500 mg/kg feed9–107WE: 5Yoshida et al. (1971)
1000 mg/kg feed9–107Y: >7; A: >7; WE: 7 < x < 12
BioassayY: 0.33, A: 0.1 mg/kgNSIM*50 000 mg/kg†† bw*7–161Y: 8; A: 10Roudaut and Moretain (1990)
ErythromycinEU: approved USA: approvedEU: 150 μg/kg; USA: 25 μg/kgBioassayY: 0.04; A: 0.01 mg/kgNSWater220 mg/L7–165Y: 6; A: 2Roudaut and Moretain (1990)
500 mg/L7–165Y: 7; A: 3
BioassayY: 0.1; A: 0.05 mg/kgNS500 mg/LNS7Y: 10; A: 6Yoshimura et al. (1978)
LC/MS0.2 μg/kg0.5 μg/kg1500 mg/L 20% erythromycinNS5WE: >3Bogialli et al. (2009a)
BioassayY: 0.04; A: 0.01 mg/kgNSFeed400 mg/kg feed7–167Y: 5; A: 2Roudaut and Moretain (1990)
JosamycinEU: not approved USA: not approvedNoneBioassayA: 0.3; Y: 0.6 IU/gNSWater225 mg/L7–165Y: 2; A: 0Roudaut and Moretain (1990)
KitasamycinEU: not approved USA: not approvedNoneBioassayY: 0.75; A: 0.3 mg/kgNSWater500 mg/LNS7Y: 4; A: 3Yoshimura et al. (1978)
OleandomycinEU: not approved USA: not approvedNoneBioassayY: 0.75; A: 0.4 mg/kgNSWater500 mg/LNS7Y: 13 A: 10Yoshimura et al. (1978)

Nitrofurans.  Nitrofurans are synthetic bacteriostatic agents that are identified by their common 5-nitrofuran ring (Botsoglou & Fletouris, 2001; Papich & Riviere, 2001). In most countries, nitrofurans are banned from use in food animals for their carcinogenic and genotoxic properties (Botsoglou & Fletouris, 2001; Dowling, 2006). Before they were banned, nitrofurans were commonly used as feed additives and to treat and prevent bacterial infections in food animals (Botsoglou & Fletouris, 2001; Vass et al., 2008). Nitrofurans are most effective against gram-negative bacteria, but they also exhibit activity against gram-positive bacteria and some protozoa (Papich & Riviere, 2001; Vass et al., 2008). In both birds and mammals, nitrofurans are rapidly metabolized following oral administration and the majority of a dose is quickly eliminated in the urine, but metabolites bind easily to tissues and can persist at low concentrations for weeks following treatment (Craine & Ray, 1972; Bishop, 2001; Botsoglou & Fletouris, 2001; Papich & Riviere, 2001; Vass et al., 2008). The rapid metabolism of nitrofurans has made screening for parent drugs difficult in food products, but the development of assays that can detect nitrofuran metabolites have been used to demonstrate the persistence of residues in egg yolk and albumen (McCracken et al., 2001; Stachel et al., 2006) (Table 5).

Table 5.   Nitrofuran residues in eggs following treatment of laying hens
NitrofuransApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; treated water was provided on days 1–3, 5 and 7; AOZ: 3-amino-2-oxazolidinone, marker residue for furazolidone; §furazolidone given with an equal concentration (0.04%) chloramphenicol in the feed; AMOZ: 3-amino-5-methyl-morpholino-2-oxazolidinone, marker residue for furaltadone; **diet in this study contained 100 mg/kg each of furaltadone, nitrofurazone, nitrofuantoin and sulfaquinoxaline.

FurazolidoneEU: prohibited USA: prohibitedNoneColorimetricNS*NSWater50 mg/L (20 mg/hen)125WE: 3Krieg (1972)
100 mg/L (10–20 mg/hen)128WE: 7
LC/MS-MS*AOZ 0.03 μg/kgNSFeed7.5 mg/kg bw*NS5WE: 5Stachel et al. (2006)
HPLC*1 μg/kgNS100 mg/kg feed1628WE: 9Botsoglou et al. (1989)
200 mg/kg feed1614WE: 10
400 mg/kg feed1614WE: 11
LC/MS*AOZ§ 1.0 μg/kgNot given400 mg/kg feedNS11WE: >21McCracken et al. (2001)
ColorimetricNSNS400 mg/kg feed127WE: 6Krieg (1972)
400 mg/kg feed1214WE: 6
HPLC*5 μg/kgNot given30 mg/henNS1WE: >5Beek and Aerts (1985)
NS0.01 mg/kg400 mg/kg§7.514WE: 5Petz (1984)
ColorimetricNSNSGavage20 mg/hen128WE: 5Krieg (1972)
50 mg/hen128WE: 5
FuraltadoneEU: prohibited USA: prohibitedNoneHPLC1.0 μg/kgNSWater107 mg/LNS6WE: >4Kumar et al. (1994)
LC/MS-MSAMOZ 0.05 μg/kgNSFeed7.5 mg/kg bwNS>5WE: >5Stachel et al. (2006)
HPLC5 μg/kgNS100 mg/kg feed**97Y: 6; A: 2Petz (1993)
NitrofurazoneEU: prohibited USA: prohibitedNoneLC/MS1.7 μg/kgNSFeed300 mg/kg feedNS16WE: >16Cooper et al. (2008)
HPLC5 μg/kgNS100 mg/kg feed**97Y: 7; A: 9Petz (1993)
Colorimetric≤0.03 mg/kgNS80 mg/kg feedNS6WE: 18Palermo and Gentile (1975)
NitrofurantoinEU: prohibited USA: prohibitedNoneHPLC1 μg/kgNSFeed100 mg/kg feed**97Y: 0; A: 6Petz (1993)

Polymyxins.  Polymyxins are polypeptide antibiotics that are effective against gram-negative bacteria. Polymyxins are most commonly used topically, as systemic use is associated with nephrotoxicity and respiratory paralysis (Riviere & Spoo, 2001). Colistin (polymyxin E), the only polymyxin for which egg residue data are available, is not well absorbed from the GI tract (Botsoglou & Fletouris, 2001), and residues were not detectable in eggs of hens given colistin in drinking water (Roudaut, 1989a) (Table 6). However, bioavailability is much higher when colistin is given IM or SC (Botsoglou & Fletouris, 2001). When laying hens were given colistin through IM injection, residues were still detectable in eggs after 7 days (the duration of the study) (Roudaut, 1989a). Excretion of metabolized drug is primarily renal in mammals (Botsoglou & Fletouris, 2001). Excretion pathways have not been described in avian species, but following SC injection of colistin (with amoxicillin) in turkeys, residues persisted much longer in kidneys than in other tissues (Tomasi et al., 1996).

Table 6.   Residues of miscellaneous drugs in eggs following treatment of laying hens
DrugApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Time until residues no longer detected (days from last treatment)Source
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; colistin sulphate used.

ColistinEU: approved; USA: not approved300 μg/kg (EU)BioassayY: 3 IU/g (0.1 mg/kg); A: 6 IU/g (0.2 mg/kg)NS*Water1 000 000 IU/L (3 mg/kg bw*)14–155Y: 0; A: 0; WE: 0Roudaut (1989a)
IM*1.67 mg/kg bw14–151Y: 7; A: 0; WE: >7

Quinolones and fluoroquinolones.  Quinolones (e.g. oxolinic acid) and their synthetic flouride-containing derivatives, fluoroquinolones (e.g. enrofloxacin, sarafloxacin), share a common core structure and activity against gram-negative microbes; fluoroquinolones are additionally effective against some gram-positive organisms (Bishop, 2001; Botsoglou & Fletouris, 2001; Martinez et al., 2006). Flouroquinolones are prohibited from extra-label use in food-producing animals in the US.

Oxolinic acid, the only quinolone for which data are available for laying hens, has high oral bioavailability and is quickly absorbed in the GI tract and widely distributed to tissues (EMEA, 1998a; Hamamoto et al., 2001). Excretion is via both urine and faeces in chickens and mammals (EMEA, 1998a). Residues persist in both tissues and eggs for several days (EMEA, 1998a; Roudaut, 1998).

Orally administered fluoroquinolones are quickly absorbed, with bioavailability generally around 50–60% (Ding et al., 2001; Anadon et al., 1992, 2002; Varia et al., 2009). Metabolism and distribution to tissues is extensive (Anadon et al., 1992, 2001, 2002), and elimination half-lives are generally between 3 and 8 h, with some variation (Ding et al., 2001; Anadon et al., 2002; Kalaiselvi et al., 2006; Silva et al., 2006; Varia et al., 2009). Elimination pathways of fluoroquinolones have not been explicitly studied in avian species, but following oral administration to chickens, residues of parent fluoroquinolones and metabolites are found in both liver and kidney (Anadon et al., 2001, 2002, 2008a). In mammals, route of elimination varies with drug. Of the compounds listed in Table 7, enrofloxacin is eliminated via the renal system, perfloxacin through the hepatic system, and danofloxacin, norfloxacin, and ciprofloxacin are excreted through both renal and hepatic pathways (Martinez et al., 2006). When given orally or by IM injection to laying hens, fluoroquinolone residues appear in eggs around 24 h after the first dose and persist in both yolk and albumen for several days after cessation of treatment (Maxwell et al., 1999; Lolo et al., 2005; Herranz et al., 2007).

Table 7.   Fluoroquinolone residues in eggs following treatment of laying hens
FluoroquinolonesApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; treatment was a commercial 10% enrofloxacin solution; a commercial 5% enrofloxacin preparation was used; §n < 5 or not specified; treatment was with a commercial preparation of 23.3 mg/mL enrofloxacin; **hens treated with a solution of 5% active compound; ††treatment was with a commercial preparation of 100 mg/mL enrofloxacin; ‡‡14C-labelled sarafloxacin hydrochloride was administered; §§a commercial preparation of 88.5% sarafloxacin hydrochloride was used; ¶¶danofloxacin methanesulphonate was dissolved in drinking water; ***a 7% norfloxacin nicotinate powder was added to drinking water; †††treatment was sodium oxolinate dissolved in drinking water.

EnrofloxacinEU: not approved USA: prohibitedNoneBioassayNS*NSWater5 mg/kg bw* (Turkey)8.55Y: >7; A: 7; WE: >7Delaporte et al. (1994)
10 mg/kg bw (Turkey)95Y: 13; A: 11; WE: 13
HPLC/MS*2 μg/kgNS12 mg/henNS5Y: 16; A: 16Lolo et al. (2005)
BioassayNSNS50 mg/L7.57Y: 4McReynolds et al. (2000)
50 mg/L7.59Y: >7 
ASTED-LC*0.6 μg/kg1 μg/kgOral11 mg/henNS7WE: >14§Schneider and Donoghue (2000)
Bioassay & LC/MS*NS1.5 μg/kgOral (bolus)11 mg/henNS3WE: >8Donoghue and Schneider (2003)
HPLCNS0.019 mg/kgOral5 mg/kg bw**NS5Y: 7; A: 10; WE: 10Gorla et al. (1997)
Bioassay0.096 mg/kgNS10 mg/kg bw7.53Y: 5; A: 3Ahmed et al. (1998)
HPLCY: 0.1; A: 0.2 μg/kgY: 0.4; A: 0.07 μg/kg10 mg/kg bwNS4A: >10; WE: >10§Huang et al. (2006)
PLE, LC-FLD*41 μg/kgNS10 mg/kg bw††NS4WE: >9Herranz et al. (2007)
LC/MS0.2 μg/kg0.4 μg/kg50 mg/kg bwNS3WE: >16§Bogialli et al. (2009b)
HPLC/MS2 μg/kgNSIM*15 mg/henNS5Y: 18; A: 17Lolo et al. (2005)
SarafloxacinEU: not approved USA: prohibitedNoneASTED-LC2 μg/kg3 μg/kgOral (capsule)5 mg/hen95WE: >5§Schneider and Donoghue (2000)
LSC*NSNSOral10.5 mg/hen‡‡NS5Y: 9; A: 5Shaikh and Chu (2000)
LSC10 μg/kgNS 10.5 mg/hen‡‡NS5Y: 9; A: 6Chu et al. (2000)
HPLC0.2 μg/kg1 μg/kgIM25 mg/hen§§50th week of lay3WE: >5§Maxwell et al. (1999)
CiprofloxacinEU: not approved USA: prohibitedNoneHPLCNS0.156 μg/gOral5 mg/kg bwNS5Y: 6; A: 0; WE: 6Gorla et al. (1997)
HPLC0.01 mg/kgNS10 mg/kg bwNS5WE: 9§Xie et al. (2005)
20 mg/kg bwNS5WE: 10§
DanofloxacinEU: not approved USA: prohibitedNoneHPLCNS5 μg/kgWater50 mg/L¶¶712Y: 12; A: 5Yang et al. (2006)
PefloxacinEU: not approved USA: prohibitedNoneHPLC/MS/MS*0.2 μg/kg0.5 μg/kgFeed200 mg/kg feed25th week of lay5WE: >29Shen et al. (2008)
400 mg/kg feed25th week of lay5WE: >29 
800 mg/kg feed25th week of lay5WE: >29 
FlumequineEU: not approved USA: prohibitedNoneBioassay0.05 mg/kgNSOral12 mg/kg bwNS1Y: 6; A: 3Samaha et al. (1991)
5Y: 5; A: 2
Bioassay0.04 mg/kgNS12 mg/kg7.53Y: 6; A: 4Ahmed et al. (1998)
HPLC5 mg/kgNSWater200 mg/L (40 mg/hen)NS5Y: 12; A: 10§Riberzani et al. (1993)
Bioassay0.05 mg/kgNSIM12 mg/kg bwNS1Y: 6; A: 2Samaha et al. (1991)
5Y: 5; A: 2
NorfloxacinEU: not approved USA: prohibitedNoneHPLC2.5 mg/kgNSWater175 mg/L***NS5Y: >6; A: >6Rolinski et al. (1997)
Oxolinic acidEU: not approved USA: not approvedNoneHPLCNS5 μg/kgWater0.5 g/L (12 mg/kg bw)†††NS5Y: 7; A: 10; WE: 9Roudaut (1998)
Feed300 mg/kg feed (13 mg/kg bw)†††NS5Y: 8; A: 9; WE: 9

Sulfonamides.  Sulfonamides as a group are synthetic compounds derived from sulfanilamide that share a common mode of action, but vary widely in their chemical characteristics, usual route of administration, and pharmacokinetics (Bishop, 2001). Sulfonamides’ antimicrobial activity arises from their ability to inhibit parts of the microbe’s folic acid pathway, which interferes with DNA synthesis (Botsoglou & Fletouris, 2001). Sulphonamides are effective against gram-positive and gram-negative bacteria, protozoa, and coccidia. In many cases, sulfonamides are combined with diaminopyrimidine potentiators such as trimethoprim, and with other coccidiostats and adjuvants to increase effectiveness (Botsoglou & Fletouris, 2001). Side effects of sulfonamides in poultry can include renal damage caused by precipitates forming in the urine, regurgitation after oral administration, and vitamin K deficiency (Frazier et al., 1995; Bishop, 2001; Botsoglou & Fletouris, 2001). In general, sulfonamides are absorbed moderately well from the GI tract, depending on solubility, and absorption occurs more rapidly in birds than mammals (Botsoglou & Fletouris, 2001). Absorbed sulfonamides distribute widely to tissues, and the main excretion pathway in both mammals and birds is via the kidneys, although some excretion also occurs via faeces (Frazier et al., 1995; Botsoglou & Fletouris, 2001).

In poultry, the most common route of administration is oral, in feed or water. Residues generally appear to persist longer in egg yolk that albumen (Table 8), although sulfonamides are initially deposited at higher concentrations in the albumen compared with the yolk following treatment (Romvary & Simon, 1992; Atta & El-zeini, 2001; Roudaut & Garnier, 2002; Tansakul et al., 2007). The concentration of sulfonamides in albumen drops exponentially after about 1 day following treatment, but declines more slowly in yolk, likely attributable to the deposition of residues in yolks in several stages of development (Furusawa et al., 1998).

Table 8.   Residues of sulfonamides and dihydrofolate reductase inhibitors in eggs following treatment of laying hens
SulphonamidesApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; atreatments prepared using a 33% aqueous solution of sodium sulphadimidine; bmedication given on days 1, 2, 5, 6 and 10; c< 5, or not given; dtreatment was sulfadimethoxine sodium salt; etreatment was with a 25% aqueous solution of sulfadimethoxine; fthe doses in the feed were made up of sulfadimethoxine and ormetroprim together in a 5:3 ratio; gsulphadimethoxine and pyrimethamine given together in this study; hmedication given on days 1, 2, 6 and 7; itreatment was a commercial liquid preparation of 3.44 g sulfaquinoxaline/100 mL; jmedicated feed was prepared using sulphaquinoxaline sodium salt; kmedication given on days 1, 2, 6, 7, 11 and 12; lsulfaquinoxaline given with nitrofurazone, nitrofurantoin and furaltadone each at 100 mg/kg feed; msulfaquinoxaline, ethopabate and amprolium were given together in the feed at 60, 5 and 100 mg/kg respectively; nsulfaquinoxaline and diaveridine given together in a 4:1 ratio in this study; oa single day of treatment is implied but not explicitly stated; ppreparation was 10% sulfamethoxazole-free base mixed with starch powder; qan aqueous preparation of sulfamethoxazole monoethanolamine at an equivalent concentration of 100 mg free base/mL was used; rproportions of the two drugs were not specified; sa preparation of 8% trimethoprim and 40% sulphadiazine was given; tsulfaquinoxaline, sulfadimidine and sulfamerazine were given in a 3:5:5 ratio; unumber of days until no residues were detectable of any of the three drugs administered. Depletion information was not provided for individual drugs.

Sulphadimidine (sulfamethazine)EU: not approved USA: not approvedNoneHPLC*NS*0.005 mg/kgWater1000 mg/La (81 mg/kg bw*)NS5Y: 15; A: 12; WE: 13Roudaut and Garnier (2002)
2000 mg/La (120 mg/kg bw)NS5Y: 14; A: 20; WE: 18
HPLC0.09 mg/kg0.3 mg/kg2000 mg/L106WE: 10Ivona et al. (2004)
ColorimetricY: 2, A: 1 mg/kgNS1000 mg/LNS8Y: 9; A: 7Blom (1975)
ColorimetricNSNS1000 mg/L245bWE: 5Krieg (1966)
1000 mg/L248Y: 8; A: 7; WE: 8
HPLC0.02 mg/kgNSOral (bolus)100 mg/kg bwNS5WE: >7cNouws et al. (1988)
HPLC0.02 mg/kg0.05 mg/kg 1 mg/kg bw5.5–6.51Y: 0; A: 1Tansakul et al. (2007)
    3 mg/kg bw5.5–6.51Y: 2; A: 1
    10 mg/kg bw5.5–6.51Y: 5; A: 1
    30 mg/kg bw5.5–6.51Y: 8; A: 3
    100 mg/kg bw5.5–6.51Y: 9; A: 7
HPLC0.05 mg/kgNSOral (capsule)100 mg/kg bw121WE: >8Geertsma et al. (1987)
    100 mg/kg bw125WE: >8c
SulphadimethoxineEU: not approved USA: not approvedNoneColorimetric0.05 mg/kgNSWater400 mg/Ld64Y: 10; A: 7cYamamoto et al. (1979)
HPLCNS0.005 mg/kg500 mg/Le (46 mg/kg bw)NS5Y: 14; A: 15; WE: 15Roudaut and Garnier (2002)
BioassayNSNS500 mg/L7.59WE: 0McReynolds et al. (2000)
HPLC0.01 mg/kgNSFeed10 mg/kg feed7.514Y: 6; A: 1Nagata et al. (1992b)
HPLC0.01 mg/kgNS25 mg/kg feed form?721Y: 6; A: 2cNagata et al. (1989)
HPLC0.01 mg/kgNS 721Y: 6; A: 2cNagata et al. (1992a)
HPLC0.01 mg/kgNS50 mg/kg feed 21Y: 6; A: 2cNagata et al. (1989)
HPLC0.01 mg/kgNS 721Y: 6; A: 2cNagata et al. (1992a)
HPLC0.01 mg/kgNS100 mg/kg feed721Y: 7; A: 4cNagata et al. (1989)
HPLC0.01 mg/kgNS 721Y: 7; A: 4cNagata et al. (1992a)
HPLC0.01 mg/kgNS400 mg/kg feed65Y: 9; A: 7; WE: 8Furusawa et al. (1994)
Colorimetric0.1 mg/kgNSFeed2000 mg/kg feed1230Y: >10; A: 5Onodera et al. (1970)
LSC*0.01 mg/kgNSFeed0.02% (13.3 mg/kg bw) (Chicken)f814Y: 14; A: 4; WE: 9cLaurencot et al. (1972)
0.01% (13.4 mg/kg bw) (Turkey)f1114Y: 15; A: 7; WE: 14c 
HPLC0.01 mg/kgNSFeed10 mg/kg feedg7.514Y: 7; A: 3Nagata et al. (1992b)
SulfaguanidineEU: not approved USA: not approvedNoneFAST-LC*10 μg/kgNSOral (capsule)90 mg/henNS1Y: 12; A: >3; WE: 10cAerts et al. (1986)
180 mg/henNS1WE: >10c
SulfamerazineEU: not approved USA: not approvedNoneColorimetric0.1 mg/kgNSFeed2000 mg/kg feed1230Y: 4; A: 4Onodera et al. (1970)
SulfaquinoxalineEU: not approved USA: not approvedNoneLC-MS*9 μg/kg11 μg/kgWater250 mg/LNS4hWE: >9cCavaliere et al. (2003)
ColorimetricY: 0.161, A: 0.167 mg/kgNS400 mg/L (53.6 mg/kg bw)NS3Y: 9; A: 7Romvary and Simon (1992)
ColorimetricY: 2, A: 1 mg/kgNS400 mg/LNS8Y: 14; A: 9Blom (1975)
ColorimetricNSNS326 mg/Li103Y: 12; A: 10Rana et al. (1993)
LSCNSNSOral6.2 mg/kg bwNS5Y: 15; A: 11Shaikh and Chu (2000)
HPLC0.01 mg/kgNS200 mg/kg feedj77Y: 10; A: 6; WE: 9cFurusawa et al. (1998)
ColorimetricNSNS200 mg/kg bwNS1WE: >5Schlenker and Simmons (1950)
Feed125 mg/kg feedNS10WE: >4
500 mg/kg feedNS10WE: >4
Colorimetric0.1 mg/kgNS500 mg/kg18–3012kY: >5; A: >5Righter et al. (1970)
1000 mg/kg feed18–3010WE: >4
NSNSFeed100 mg/kg feedl97Y: 10; A: 9Petz (1993)
0.01 mg/kgNSFeed60 mg/kgm5.514WE: 12Nose et al. (1982)
0.03 mg/kgNSWater0.6%nNS1oY: 6; A: >5Sakano et al. (1981)
SulphamonomethoxineEU: not approved USA: not approvedNoneHPLC0.01 mg/kgNSFeed25 mg/kg feed721Y: 4; A: 2cNagata et al. (1989)
HPLC0.01 mg/kgNS721Y: 4; A: 2cNagata et al. (1992a)
HPLC0.01 mg/kgNS50 mg/kg feed721Y: 4; A: 2cNagata et al. (1989)
HPLC0.01 mg/kgNS721Y: 4; A: 2cNagata et al. (1992a)
HPLC0.01 mg/kgNS100 mg/kg feed721Y: 7; A: 2cNagata et al. (1989)
HPLC0.01 mg/kgNS721Y: 7; A: 2cNagata et al. (1992a)
HPLC0.01 mg/kgNS400 mg/kg feed5Y: 8; A: 5; WE: 8Furusawa and Mukai (1995)
Colorimetric0.1 mg/kgNS50 mg/kg feed1230Y: 0; A: 0Onodera et al. (1970)
2000 mg/kg feed30Y: 10; A: 6
SulphanilamideEU: not approved USA: not approvedNoneColorimetricY: 2; A: 1 mg/kgNSWater1000 mg/LNS8Y: 17; A: 14Blom (1975)
0.04 mg/kgNSOral (capsule)75 mg/kg bw1Y: >7; A: 6cShaikh et al. (1999)
LSCNSNSOral105.6 mg/kg bwNS1Y: 9; A: 6cShaikh and Chu (2000)
SulfamethoxazoleEU: not approved USA: not approvedNoneColorimetric0.16 mg/LNSSC*50 mg/kg bwNS1Y: 10; A: 8Romvary et al. (1988)
FlourometricNS0.1 mg/kgFeed2000 mg/kg feedp7–105Y: >10; A: 5Oikawa et al. (1977)
4000 mg/kg feedp7–105Y: >10; A: 7
IM*200 mg/kg bwq7–105Y: >10; A: 7
Sulfadimethoxine & ormetoprim  BioassayNSNSFeed250 mg/kgr7.59WE: 0McReynolds et al. (2000)
DiaveridineEU: not approved USA: not approvedNone 0.04 mg/kgNSWater0.6%nNS1Y: 7; A: >6Sakano et al. (1981)
SulphadiazineEU: not approved USA: not approvedNoneHPLC0.02 mg/kgNSWater0.2 g/L6.55Y: 4; A: 5Atta and El-zeini (2001)
0.4 g/L6.55Y: 6; A: 7
TrimethoprimEU: not approved USA: not approvedNoneHPLC0.02 μg/gNSWater0.2 g/Ls6.55Y: 5; A: 4Atta and El-zeini (2001)
0.4 g/Ls6.55Y: 7; A: 6
HPLC0.02 mg/kgNSFeed4 mg/kg feed1119Y: 4; A: 0Nagata et al. (1991)
16 mg/kg feed1119Y: 10; A: 2
56 mg/kg feed1119Y: 11; A: 8
OrmetoprimEU: not approved USA: not approvedNone 0.01 mg/kgNSFeed0.02% (7.8 mg/kg bw) (Chicken)2414Y: 8; A: 4; WE: 8cLaurencot et al. (1972)
 0.01% (7 mg/kg bw) (Turkey)1114Y: 14; A: 3; WE: 13c
Sulphaquinoxaline: Sulphadimidine: SulphamerazinetEU: not approved USA: not approved ColorimetricY: 0.161, A: 0.167 mg/kgNSWater390 mg/L (56.9 mg/kg bw)NS3Y: 5; A: 2uRomvary and Simon (1992)
Colorimetric0.16 mg/kgNS300 mg/LNS3Y: 6; A: 3Romvary et al. (1988)
PyrimethamineEU: not approved USA: not approvedNoneHPLC0.02 mg/kgNS 1 mg/kg feedf7.514Y: 10; A: 3Nagata et al. (1992b)
0.02 mg/kgNS 1 mg/kg feed7.514Y: 11; A: 2
ColorimetricY: 1, A: 0.5 mg/kgNSWater0.01%NS8Y: >20; A: 9Blom (1975)
HPLC0.02 mg/kgNSFeed0.1 mg/kg feed721Y: 2; A: 0cNagata et al. (1990)
1 mg/kg feed721Y: 9; A: 0c
10 mg/kg feed721Y: 12; A: 5c

Sulfonamide synergists.  Poultry are often treated with sulfonamides in combination with other anti-protozoal agents to increase efficacy; these ‘sulfonamide synergists’ are combined with sulfonamides in Table 8. Dihydrofolate reductase/thymidylate synthase inhibitors (e.g. trimethoprim, ormetoprim, pyrimethamine) and diaveridine, a pyrimidine derivative, act synergistically with sulfonamides to treat coccidial infections. The limited data available on the kinetics of these compounds in birds suggest that following oral administration, bioavailability can range from 35–80%, and the drugs are widely distributed throughout the body (Fellig et al., 1971; Cala et al., 1972; Queralt & Castells, 1985; Loscher et al., 1990; Baert et al., 2003). Avian species rapidly eliminate trimethoprim and ormetoprim from the body (Fellig et al., 1971; Romvary & Horvay, 1976), while pyrimethamine appears to persist in the blood and tissues for a prolonged period (Blom, 1975). There is little information on the excretion pathways of the dihydrofolate reductase/thymidylate synthase inhibitors in avian species. In mammals, excretion is primarily renal (Lindsay & Blagburn, 2001). Trimethoprim, ormetoprim and pyrimethamine residues have all been detected in both yolk and albumen of eggs laid more than a week after treatment has ended (Table 8).

Tetracyclines.  Tetracyclines are naturally occurring products of fungi in the genus Streptomyces, or semi-synthetic derivatives of such products (Chopra & Roberts, 2001). Drugs in this class are widely used in food animals for disease prevention and treatment, as well as growth promotion in countries where such use is legal (Botsoglou & Fletouris, 2001; Chopra & Roberts, 2001). Tetracyclines are effective against a broad spectrum of gram-positive and gram-negative bacteria, Mycoplasma, Chlamydophila, and Rickettisa spp. (Bishop, 2001; Botsoglou & Fletouris, 2001). The most common and practical method of administration of tetracyclines to poultry is via feed or water. In general, tetracyclines are absorbed moderately well by the digestive system in mammals, but absorption may be less complete in birds (Anadon et al., 1994b; Botsoglou & Fletouris, 2001). Absorption depends on the lipophilicity of the compound; oxytetracycline is the least lipophilic and therefore the most poorly absorbed following oral administration, and doxycycline is the most lipophilic of the tetracyclines (Botsoglou & Fletouris, 2001). Tetracyclines have a high affinity for metallic ions such as calcium, iron, magnesium and zinc (Bishop, 2001; Botsoglou & Fletouris, 2001), which will impede absorption if present in feed or the digestive system. Once tetracyclines are absorbed, they are distributed throughout the body and concentrate in the liver and kidney. In both birds and mammals, tetracyclines are excreted through the renal and biliary systems (Frazier et al., 1995).

Tetracyclines are also deposited in the eggs of laying hens. Residues appear more rapidly in egg albumen than yolk following drug administration, but concentrations reach higher levels and persist longer in egg yolk (Yoshida et al., 1973c; Roudaut et al., 1989; Omija et al., 1994; Zurhelle et al., 2000). The residue levels reached, and the rate of their depletion from eggs depends on the method of administration, the dose and the specific drug given. Doxycycline is deposited into eggs at higher levels than tetracycline, and tetracycline reaches higher concentrations than oxytetracycline, when the same dose and route are used (Nogawa et al., 1981; Roudaut et al., 1989; Yoshimura et al., 1991). Variation in the persistence of residues in eggs may reflect differences in absorption among drugs (Table 9). Doxycycline was detected in eggs for almost a month following cessation of the medication (Yoshimura et al., 1991), while following a similar dosage regimen of oxytetracycline, residues were detected for 4–10 days (Nogawa et al., 1981; Yoshimura et al., 1991).

Table 9.   Tetracycline residues in eggs following treatment of laying hens
TetracyclinesApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; drug provided in the form of its hydrochloride salt; n < 5 or not given; §a commercial oxytetracylcine preparation of 100 mg/mL was used; a commercial preparation of 800 mg/g oxytetracycline hydrochloride was used; **a commercial preparation of 800 mg/g doxycycline hydrochloride was used.

OxytetracyclineEU: approved USA: not approvedEU: 200 μg/kgBioassayY: 0.2, A: 0.07 mg/kgNS*Water0.1 g/L (10 mg/kg bw*)NS5Y: 0; A: 0Roudaut et al. (1987a)
0.25 g/L (25 mg/kg bw)5Y: 4; A: 3
Bioassay0.05 mg/kgNS0.4 g/L127Y: 3; A: 0Omija et al. (1994)
BioassayY: 0.3, A: 0.075 mg/kgNS0.5 g/LNS7WE: 4Nogawa et al. (1981)
BioassayY: 0.2, A: 0.07 mg/kgNS0.5 g/L (50 mg/kg bw)NS5Y: 4; A: 3Roudaut et al. (1987a)
BioassayY: 0.3, A: 0.07 mg/kgNS0.5 g/L§NS7Y: 10; A: 6Yoshimura et al. (1991)
Bioassay0.05 mg/kgNS0.6 g/L127Y: 5; A: 1Omija et al. (1994)
0.8 g/L127Y: 5; A: 2
HPLC*0.05 mg/kgNS2 g/LNS7Y: 12; A: 9Nagy et al. (1997)
Bioassay5 mg/kgNS125 mg/hen9.55WE: 19Frieser et al. (1986)
Bioassay0.27 mg/kgNSFeed20 mg/kg feed87Y: 0; A: 0Yoshida et al. (1973b)
Bioassay0.08 mg/kg0.1 mg/kg25 mg/kg feed628WE: 0Katz et al. (1973)
50 mg/kg feed628WE: 0
BioassayY: 258, A: 117 μg/kgNS50 mg/kg feed145Y: 0; A: 0Donoghue and Hairston (1999)
Bioassay0.08 mg/kg0.1 mg/kg100 mg/kg feed628WE: 0Katz et al. (1973)
BioassayY: 258, A: 117 μg/kgNS200 mg/kg feed145Y: 0; A: 1Donoghue and Hairston (1999)
BioassayY: 0.2, A: 0.07 mg/kgNS300 mg/kg feed (18 mg/kg bw)NS7Y: 2; A: 1Roudaut et al. (1987a)
BioassayY: 0.2, A: 0.07 mg/kgNS600 mg/kg feed (36 mg/kg bw)NS7Y: 4; A: 2Roudaut et al. (1987a)
HPLC2.2 μg/kg13 μg/kg800 mg/kg feed167WE: >10De Ruyck et al. (1999)
Bioassay0.27 mg/kgNS4000 mg/kg feed87Y: 5; A: 2Yoshida et al. (1973b)
BioassayY: 0.2, A: 0.07 mg/kgNSIM*15 mg/kg bwNS3Y: 7; A: 5Roudaut et al. (1987a)
30 mg/kg bwNS3Y: 11; A: 9
HPLC0.05 mg/kgNS200 mg/kg bwNS5Y: 12; A: 5Nagy et al. (1997)
ChlortetracyclineEU: approved; USA: approved200 μg/kg (EU); 0.4 mg/kg (USA)BioassayY: 0.06, A: 0.012 mg/kgNSWater0.5 g/LNS7WE: 6Nogawa et al. (1981)
Bioassay2.5 mg/kgNS125 mg/hen9.55WE: 24Frieser et al. (1986)
LC-APCI-MS*NSNSFeed300 mg/kg feed (120 g/hen)99WE: >9Kennedy et al. (1998b)
BioassayY: 0.06, A: 0.01 mg/kgNS600 mg/kg feed (36 mg/kg bw)NS7Y: 9; A: 5; WE: 9Roudaut et al. (1989)
HPLC & LC/MS-MS*10 μg/kgNS1000 mg/kg feedNS17Y: >5; A: >4Zurhelle et al. (2000)
Bioassay0.05 mg/kgNS8000 mg/kg87Y: 5; A: 2Yoshida et al. (1973c)
Bioassay0.025 mg/kgNS50 mg/kg feed122–3 weeksWE: 0Raica et al. (1956)
100 mg/kg feed122–3 weeksWE: 0
200 mg/kg feed122–3 weeksWE: 0
500 mg/kg feed1216WE: 5
1000 mg/kg feed1216WE: 6
2000 mg/kg feed1216WE: 4
Bioassay3 μg/kgNS50 mg/kg feed597WE: 1Katz et al. (1972)
100 mg/kg feed597WE: 2
150 mg/kg feed597WE: 3
200 mg/kg feed597WE: 3
BioassayNSNS3 mg/kg feedNS21WE: 0Durbin et al. (1953)
10 mg/kg feedNS21WE: 0
50 mg/kg feedNS21WE: 0
100 mg/kg feedNS21WE: 0
200 mg/kg feedNS21WE: 0
2000 mg/kg feedNS21WE: 14
10 000 mg/kg feedNS21WE: 14
20 000 mg/kg feedNS21WE: 21
TetracyclineEU: approved; USA: not approved200 μg/kg (EU)BioassayY: 0.15, A: 0.07 mg/kgNSWater0.25 g/L (25 mg/kg bw)NS5Y: 6; A: 1; WE: 6Roudaut et al. (1989)
0.5 g/L (50 mg/kg bw)5Y: 9; A: 2; WE: 9
BioassayY: 0.3, A: 0.075 mg/kgNS500 μg/mLNS7WE: 5Nogawa et al. (1981)
Bioassay5 μg/kgNS125 mg/hen9.55WE: 23Frieser et al. (1986)
BioassayY: 0.15, A: 0.07 mg/kgNSFeed300 mg/kg feed (18 mg/kg bw)NS7Y: 8; A: 1; WE: 8Roudaut et al. (1989)
600 mg/kg feed (36 mg/kg bw)7Y: 11; A: 2; WE: 11
DoxycyclineEU: not approved; USA: not approvedNoneBioassayY: 0.15 A: 0.04 mg/kgNSWater0.5 g/L**NS7Y: 27; A: 25Yoshimura et al. (1991)

Endoparasiticides

Anthelmintics.  As a class, anthelmintics are used to treat helminth parasite infections, but anthelmintic drugs are diverse in their structures and mechanisms of action (Barragry, 1984b; McKellar & Jackson, 2004). Benzimidazoles (flubendazole and albendazole), levamisole and ivermectin are the only anthelmintics for which egg residue data are available (Table 10). Flubendazole is used to treat nematodes in many food animal species, including poultry (Botsoglou & Fletouris, 2001). Following oral administration to chickens, flubendazole and albendazole are absorbed relatively quickly, reaching peak plasma concentrations in 2–4 h (Csiko et al., 1996; EMEA, 1999, 2006). In chickens, tissue concentrations of flubendazole following oral administration are highest in the liver and kidney, suggesting that at least some excretion occurs via the urine (Botsoglou & Fletouris, 2001). Despite a rapid rate of elimination, detectable residues of flubendazole and albendazole can be found in eggs laid up to a week or more after treatment (Table 10) (Csiko et al., 1995; Kan et al., 1998). Residues are more persistent in the egg yolk than albumen (Csiko et al., 1995; Kan et al., 1998; Botsoglou & Fletouris, 2001).

Table 10.   Residues of anthelmintic drugs in chicken eggs following treatment of laying hens
AnthelminticsApproval status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; prepared using a commercial 5% premix; treatment was with levamisole hydrochloride.

FlubendazoleEU: approved; USA: not approvedEU: 400 μg/kgHPLC*0.3 mg/kg0.6 mg/kgFeed2.6 mg/kg feed621WE: 0Kan et al. (1998)
9.4 mg/kg feed621WE: 6
27 mg/kg feed621WE: >6
LevamisoleEU: not approved; USA: not approvedNoneHPLC0.001 mg/kg0.025 μg/gOral40 mg/kg bw*81WE: 14El-Kholy and Kemppainen (2005)
IvermectinEU: not approved; USA: not approvedNoneHPLC0.5 μg/kgNSFeed0.1 mg/kg feed621WE: 0Keukens et al. (2000)
0.4 mg/kg feed621Y: 6; A: 0
0.8 mg/kg feed621Y: >6; A: 0
AlbendazoleEU: not approved; USA: not approvedNoneHPLC10 μg/kgNSWater10 mg/kg bw91Y: 8; A: 4Csiko et al. (1995)

Levamisole is used for treating nematode infections, but is ineffective against cestodes or trematodes (Botsoglou & Fletouris, 2001). In mammals, levamisole is well absorbed when given orally and is excreted relatively rapidly in the urine (Barragry, 1984a). There are no data available on the absorption or primary excretion pathways of levamisole in birds, but the drug concentrates in the liver following oral dosing in chickens (FAO/WHO, 1991), and residues are found in the eggs of laying hens for up to 2 weeks after treatment (El-Kholy & Kemppainen, 2005).

Ivermectin, a mixture of two avermectins, is effective against nematodes and arthropod pests, but not cestodes or trematodes (Botsoglou & Fletouris, 2001). There is very little information on the metabolism of ivermectin in avian species, but it is well studied in mammals. Regardless of route of administration, ivermectin is widely distributed to tissues. Because of its lipophilicity, ivermectin can accumulate in fat, where it can persist for prolonged periods (Canga et al., 2009). Ivermectin is not highly metabolized and excretion is primarily via the faeces (Canga et al., 2009). When ivermectin is administered to laying hens, residues are preferentially deposited in the egg yolk (Keukens et al., 2000) and can be found in eggs laid for several days following cessation of treatment (Table 10).

Coccidiostats

Drugs used as anti-coccidials come from a number of different drug classes and have a corresponding variety of excretion and disposition patterns in poultry. It should be noted that many anti-coccidials, such as nitroimidazoles, ionophores, triazines, and sulfonamides, also have antibacterial properties.

Nitroimidazoles.  The nitroimidazoles (dimetridazole, ronidazole, ipronidazole) are active against gram-negative and gram-positive anaerobic bacteria as well as protozoa (Edwards, 1993; Bishop, 2001). However, nitroimidazoles are suspected mutagens and carcinogens, and their use in food animals is limited (Botsoglou & Fletouris, 2001; Dowling, 2006). In avian species, nitroimidazoles are rapidly absorbed from the GI tract and widely distributed to tissues (Rosenblum et al., 1972; Herman et al., 1989; FAO/WHO, 1990; Aerts et al., 1991; Posyniak et al., 1996b). Excretion occurs via the faeces and urine in birds and mammals (Rosenblum et al., 1972; Morton et al., 1973; Aerts et al., 1991; Dowling, 2006). Ronidazole is excreted mostly unchanged, while ipronidazole and dimetridazole are more extensively metabolized (Aerts et al., 1991; Polzer et al., 2004).

When given orally to laying hens, dimetridazole and ronidazole are deposited in eggs at higher concentrations than ipronidazole, and residues of all three drugs are distributed uniformly between yolk and albumen (Mortier et al., 2005) (Table 11).

Table 11.   Residues of anticoccidial drugs in eggs following treatment of laying hens
CoccidiostatsApproval Status (laying hens)*Tolerance/maximum residue limit*Analytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; feed prepared using a commercial 6% salinomycin premix; medicated feed prepared using a commercially available 12% salinomycin sodium; §nicarbazin and narasin were used in combination, in a commercial preparation containing 80 g/kg of each drug; prepared from a commercial liquid preparation of 9.6% amprolium; **amprolium given together with ethopabate (5 mg/kg feed) and sulfaquinoxaline (60 mg/kg feed); ††commercially available medicated feed additive containing 6 g/kg halofuginone hydrobromide used; ‡‡commercially available feed additive containing meticlorpindol and methylbenzoquate in a 12:1 ratio; §§n < 5 or not given; ¶¶a veterinary formulation of clazuril (Appertex®, Janssen Pharmaceutica, Beerse, Belgium) used with 2.5 mg active compound per tablet; ***commercially available medicated feed additive containing 0.2% diclazuril used; †††commercially available medicated feed additive containing 66 g/kg robenidine hydrochloride used; ‡‡‡a commercial drinking water additive containing 2.5% toltrazuril was used; §§§doses given on days 1, 2, 8 and 9.

SalinomycinEU: not approved; USA: not approvedNoneHPTLC*10 μg/kgNSFeed5 mg/kg feedNS7WE: 8Kan et al. (1990)
HPLC*5 μg/kg10 μg/kg30 μg/g feedNS14Y: >3; A: 0Akhtar et al. (1996a)
60 μg/g feedNS14Y: >3; A: 1
90 μg/g feedNS14Y: >3; A: 2
150 μg/g feedNS14Y: >3; A: 2
HPTLCY: 10, A: 7.5 μg/kgNS60 mg/kg feed145Y: >10; A: 2Šinigoj-Gačnik and Rojs (2008)
NarasinEU: not approved; USA: not approvedNoneLC-MS/MS*0.9 μg/kgNSFeed2.5 mg/kg feed1721Y: >7; A: 0Rokka et al. (2005)
HPTLC10 μg/kgNS5 mg/kg feedNS7WE: 8Kan et al. (1990)
NSNS41 mg/kg feedNS14WE: 17
NSNS2144 μg/kg feedNS14WE: 8
LSC*NSNSIC*0.62 mg (Chicken)81Y: 9Catherman et al. (1991)
0.1 mg (Quail)NS1Y: 13
LC-MS/MSNS1 μg/kg 2 mg/kg feed§8–1014WE: 12Mortier et al. (2005)
LC-MS/MSNS1 μg/kg 40 mg/kg feed§8–1014WE: 11
LasalocidEU: approved; USA: not approvedEU: 150 μg/kgLC-MS*0.3 μg/kg1 μg/kgFeed5 mg/kg feed (0.6 g/day)916WE: 10Kennedy et al. (1996)
MonensinEU: not approved; USA: not approvedNoneHPTLC10 μg/kgNSFeed5 mg/kg feedNS7WE: 0Kan et al. (1990)
AmproliumEU: approved; USA: approvedEU: None required; USA: Y: 8, WE: 4 mg/kgFluorometric0.18 mg/kgNSWater120 mg/L7–2016Y: 8Polin et al. (1968)
240 mg/L7–2016Y: 10
CF-LC*Y: 5, A: 3 μg/kgNSFeed5 mg/kg feedNS10WE: 10Kan et al. (1990)
5 mg/kg feedNS14WE: 10
HPLCY: 0.005, A: 0.003 mg/kgNS5 mg/kg feedNS14Y: >16Kan et al. (1989)
25 mg/kg feedNS14Y: >16
125 mg/kg feedNS14Y: >16
250 mg/kg feedNS14Y: >16
5 mg/kg feedNS10Y: 6
250 mg/kg feedNS10Y: >8
125 mg/kg feed5–6Hatch-1st layY: 19
Fluorometric0.18 mg/kgNS125 mg/kg feed7–2016Y: 7Polin et al. (1968)
250 mg/kg feed7–2016Y: 8
GC*0.01 mg/kgNS125 mg/kg feedNS11Y: 7Petz et al. (1980)
25 mg/kg feedNS11Y: 8
NSNS100 mg/kg feed**5.514WE: >14Nose et al. (1982)
HalofuginoneEU: not approved; USA: not approvedNoneLC-ES-MS/MS*1 μg/kgNSFeed3 μg/kg feed††514WE: 0Yakkundi et al. (2002)
LC-MS/MS & ELISA*0.5 μg/kg1 μg/kg150 μg/kg feed††8–1014WE: 8Mortier et al. (2005)
LC-ES-MS/MS1 μg/kgNS300 μg/kg feed††514WE: >14Yakkundi et al. (2002)
LC-MS/MS & ELISA0.5 μg/kg1 μg/kg1.5 mg/kg feed††514WE: 19Mortier et al. (2005)
HPLC & LC-MS/MS2 μg/kgNS3 mg/kg feed††5.514WE: 12Mulder et al. (2005)
MeticlorpindolEU: not approved; USA: not approvedNoneHPLC2 μg/kgNSFeed2 mg/kg feed‡‡ (caged)6.529A: 4Hafez et al. (1988)
2 mg/kg feed‡‡ (raised on deep litter)6.529A: 6
100 mg/kg feed‡‡ (caged)6.514A: 0
100 mg/kg feed‡‡ (raised on deep litter)6.514A: 28
CF-LCY: 20, A: 10 μg/kgNS10 mg/kg feedNS10WE: 6Kan et al. (1990)
HPLCY: 20, WE: 10 μg/kgNS10 mg/kg feed‡‡NS10WE: 6Mattern et al. (1990)
110 mg/kg feed‡‡NS10Y: 8; A: 14; WE: 14
DecoquinateEU: not approved; USA: not approvedNone NSNSFeed40 mg/kg feed5.514WE: 13Nose et al. (1982)
LSC & TLC*0.1 mg/kgNS2.6 mg/day919Y: >16; A: 1; WE: 12§§Kouba et al. (1972)
LSCNSNSFeed, IV*0.5 g/kg feed, 0.1 mg IV (Chicken)87, 1Y: >28; A: 0Seman et al. (1989)
LSCNSNSFeed, IC*0.5 g/kg feed, 0.05 IV (Quail)NS7, 1Y: >28; A: 0
ClazurilEU: not approved; USA: not approvedNoneHPLC0.09 mg/kg0.2 mg/kgOral (capsule)3 mg/kg bw¶¶9–101Y: 0; A: 0Giorgi and Soldani (2008)
3 mg/kg bw9–105Y: 10; A: 3
DiclazurilEU: not approved; USA: not approvedNoneLC-MS/MSNS0.5 μg/kgFeed50 μg/kg feed***8–1014WE: 11Mortier et al. (2005)
1 mg/kg feed***8–1014WE: 23
RobenidineEU: not approved; USA: not approvedNoneLC-MS/MSNS1 μg/kgFeed1.8 mg/kg feed†††8–1014WE: 13Mortier et al. (2005)
36 mg/kg feed†††8–1014WE: 29
NicarbazinEU: not approved; USA: not approvedNoneLC-ES-MS*NS1 μg/kgFeed12 mg/kg feed (1.44 g/day)516WE: 12Cannavan et al. (2000)
GCNSNS200 mg/kg feed5.514WE: 29Nose et al. (1982)
HPLC2 μg/kgNot given2 mg/kg feed (caged)629Y: 16Friedrich et al. (1985)
2 mg/kg feed (deep litter)629Y: >60
HPLC2 μg/kgNot given125 mg/kg feed (caged)7.57Y: 28Friedrich et al. (1984)
125 mg/kg feed (deep litter)7.57Y: >53
HPLC & GC0.01 mg/kgNS0.45–1.1 mg/kg feed0–6Hatch-1st layWE: 13Oishi and Oda (1989)
0.26 mg/kg feedNS1WE: 7
1 mg/kg feedNS1WE: 9
0.05 mg/kg feedNS10WE: >5
0.1 mg/kg feedNS10WE: 7
0.5 mg/kg feedNS10WE: 10
1 mg/kg feedNS10WE: >10
LC-MS/MS & ELISANS1 μg/kg2 mg/kg feed§8–1014WE: 15Mortier et al. (2005)
LC-MS/MS & ELISANS1 μg/kg40 mg/kg feed§8–1014WE: 24
ToltrazurilEU: not approved; USA: not approvedNoneLC-MS/MS1 μg/kgNSWater78 mg/L (9.5 mg/kg bw/day)‡‡‡5.54§§§Y: >19; A: >19; WE: >19Mulder et al. (2005)
EthopabateEU: not approved; USA: not approvedNoneNSNSFeed5 mg/kg feed**5.514WE: 0Nose et al. (1982)
Dinitolmide (Zoalene)EU: not approved; USA: not approvedNoneNSNS125 mg/kg feed5.514WE: >14Nose et al. (1982)
DimetridazoleEU: prohibited; USA: prohibitedNoneLC-MS/MS & ELISA0.5 μg/kg1 μg/kgFeed100 mg/kg feed8–1014WE: 13Mortier et al. (2005)
HPLC2 μg/kgNSOral50 mg/kg bw6.53Y: 5; A: 3; WE: 4Posyniak et al. (1996a)
250 mg/kg bw6.53Y: 6; A: 5; WE: 6
LC-MS2 μg/kg5 μg/kgOral (capsule)75 mg/bird111Y: 5; A: 5; WE: 5Aerts et al. (1991)
HPLC2 μg/kgNSIM*50 mg/kg bw6.53Y: 6; A: 5; WE: 6Posyniak et al. (1996a)
RonidazoleEU: prohibited; USA: prohibitedNoneLC-MS2 μg/kg5 μg/kg 75 mg/bird111WE: 7§§Aerts et al. (1991)
IpronidazoleEU: not approved; USA: prohibitedNoneLC-MS5 μg/kg10 μg/kg 75 mg/bird111WE: 6Aerts et al. (1991)

Ionophores.  Many polyether ionophores (e.g. lasalocid, monensin, narasin, salinomycin) are widely used anticoccidials in the poultry industry and are commonly given in feed as disease preventatives or growth promoters (Botsoglou & Fletouris, 2001). Ionophore coccidiostats are derived from bacterial fermentation products (Botsoglou & Fletouris, 2001). The anticoccidial activity of ionophores is related to their affinity for cations, which when bound to ionophore medications form lipophilic complexes that affect their transport through biological membranes (Elsasser, 1984; Botsoglou & Fletouris, 2001). Residues of the polyether ionophores in food products are of special concern because of the high degree of toxicity of these drugs to many species (Dowling, 2006).

When administered orally to chickens and quail, the available data show that ionophores are rapidly absorbed and widely distributed to tissues (Catherman et al., 1991; Atef et al., 1993; Akhtar et al., 1996a; Henri et al., 2009). Bioavailability varies among drugs from less than 30% to greater than 75% (Donoho, 1984; Atef et al., 1993; Henri et al., 2009). Metabolism is extensive (Donoho, 1984; Sweeney et al., 1996; FAO/WHO, 2008) and elimination is generally rapid, but lasalocid may persist in tissues for longer periods than other ionophores (EMEA, 2004). Narasin and monensin are known to be excreted via faeces in chickens (Donoho, 1984; FAO/WHO, 2009).

When given to laying hens, ionophores concentrate in the egg yolks to a greater extent than in the albumen (Kan & Petz, 2000; Mortier et al., 2005; Rokka et al., 2005), but residues are also detectable in albumen when drugs are given at high dosages (Akhtar et al., 1996a; Kan & Petz, 2000) (Table 11). Of the commonly used ionophores, lasalocid produces the highest residue concentrations in eggs, salinomycin produces relatively low residue levels, and monensin residues are sometimes not detectable at all in the eggs of treated hens (Kennedy et al., 1998a) (Table 11).

Triazines.  Diclazuril, clazuril, and toltrazuril are structurally similar members of the triazine group (Botsoglou & Fletouris, 2001). Diclazuril and toltrazuril are characterized by extensive distribution to tissues, long elimination half-lives and elimination via the faeces in both birds and mammals (EMEA, 1996, 1998b). While toltrazuril is relatively well absorbed from the GI tract and extensively metabolized (EMEA, 1998b), orally administered diclazuril is minimally metabolized, and the majority of the parent drug is excreted in the faeces (EMEA, 1996).

When repeated oral doses of diclazuril or toltrazuril are given to laying hens, both result in persistent residues in tissues and eggs (EMEA, 1996; Mortier et al., 2005; Mulder et al., 2005) (Table 11). While there is very little information on the pharmacokinetics of clazuril, a single study on laying hens shows that clazuril accumulates in eggs in a pattern similar to that of diclazuril (Mortier et al., 2005), persisting for many days in the eggs after treatment has ended (Giorgi & Soldani, 2008). All three compounds are deposited primarily in the egg yolk (Mortier et al., 2005; Giorgi & Soldani, 2008).

Benzamides.  Benzamide anticoccidials include dinitolmide (also called zoalene), aklomide and nitromide. Of these, dinitolmide is most widely used for treating coccidiosis in poultry (Botsoglou & Fletouris, 2001). Dinitolmide is rapidly absorbed following oral administration to chickens, and broadly and rapidly distributed to tissues (Smith et al., 1963). Following absorption, dinitolmide is extensively metabolized by the liver and excreted in faeces (Smith et al., 1963; Smith, 1964; Pan & Fouts, 1978; Botsoglou & Fletouris, 2001). The single study available on the deposition of dinitolmide in eggs did not continue sampling eggs long enough to establish the full time course of drug elimination, but drug residues were still present 2 weeks after the medication was withdrawn (Nose et al., 1982) (Table 11). Concentrations of dinitolmide residues were approximately 10 times higher in the egg yolk than the albumen (Nose et al., 1982).

Carbanilides.  The carbanilide nicarbazin is used for prevention of coccidiosis in poultry. Carbanilides are not intended for use in laying hens because they have been shown to decrease egg production (Botsoglou & Fletouris, 2001; Lindsay & Blagburn, 2001). Nicarbazin is well absorbed from the GI tract and distributed broadly to tissues when given orally to chickens. Nicarbazin is broken down into two major metabolites, 2-hydroxy-4,6-dimethylpyrimidine (HDP) and 4,4′-dinitrocarbanilide (DNC), which differ in pharmacokinetic behaviour. DNC, the marker residue used for evaluating food safety (EFSA, 2010), occurs at much higher levels than HDP and concentrates in the liver and kidneys, and is excreted primarily in the faeces, while HDP is excreted in the urine (Wells, 1999; EFSA, 2010). When given orally to laying hens, DNC is found concentrated in the egg yolk, while HDP is found predominantly in albumen (Cannavan et al., 2000; Mortier et al., 2005) (Table 11). The period during which residues are found in eggs is greatly extended if the hens are kept on litter that is not frequently changed, as shown by studies by Friedrich et al. (1984, 1985) (Table 11).

Quinolone derivatives.  Buquinolate, decoquinate and methylbenzoquate are quinolone derivatives used for the prevention of coccidiosis in poultry (Botsoglou & Fletouris, 2001). Data on drug deposition in chicken eggs exist only for decoquinate (Table 11). Decoquinate is poorly absorbed from the GI tract of chickens, but what absorption occurs is rapid, and the drug is distributed widely to tissues (Filer et al., 1969; Craine et al., 1971). Metabolism is not extensive, and excretion of the parent compound occurs via the faeces (Filer et al., 1969; Craine et al., 1971). In contrast, in mammals excretion occurs via both urine and faeces (Mitchell et al., 1988). Clearance of decoquinate occurs more slowly in chickens compared with cattle, sheep or even quail (Seman et al., 1986; Mitchell et al., 1988). When administered to laying hens, decoquinate is deposited in egg yolk (Kouba et al., 1972; Nose et al., 1982) and persists for very long periods [over 4 weeks in some studies (Seman et al., 1989)] after the end of treatment.

Other anti-coccidials.  A few anticoccidial drugs included in Table 11 (robenidine, amprolium, halofuginone, meticlorpindol (clopidol) and ethopabate) do not fall into any of the above classes. Of these, only ethopabate was not found to produce persistent drug residues in eggs (Table 11).

Robenidine is a synthetic guanidine derivative that is used to control coccidiosis in poultry and rabbits (Botsoglou & Fletouris, 2001). In chickens, it is incompletely absorbed from the GI tract, but the absorbed portion is well distributed to tissues and extensively metabolized (Zulalian et al., 1975). Excretion occurs over several days following oral administration (Zulalian et al., 1975). Residues are detected in the eggs, primarily the yolk, of treated hens for weeks after medication is withdrawn (Mortier et al., 2005) (Table 11).

Amprolium is structurally similar to vitamin B1 (Botsoglou & Fletouris, 2001). When administered orally to chickens, bioavailability is low, (Hamamoto et al., 2000), but absorbed amprolium is widely distributed to tissues (Alam et al., 1987) and rapidly eliminated in the urine and faeces (Polin et al., 1967). Amprolium administered to laying hens is deposited primarily in the egg yolk, and residues can be detected in eggs for 2 weeks or more after cessation of treatment, depending on the dose and assay sensitivity (Nose et al., 1982; Kan et al., 1989) (Table 11).

Ethopabate is a benzoic acid used in combination with amprolium to treat coccidiosis in poultry (Botsoglou & Fletouris, 2001). Ethopabate is well absorbed following oral administration to chickens and is rapidly metabolized and almost completely excreted in urine (Buhs et al., 1966). Based on the limited data available, it appears that little or no ethopabate administered orally to laying hens is deposited in eggs (Nose et al., 1982) (Table 11).

Halofuginone is a plant-derived alkaloid (Lindsay & Blagburn, 2001) that is a potent anticoccidial (Botsoglou & Fletouris, 2001). Halofuginone appears to be poorly absorbed from the GI tract in mammals, and only a small fraction of the drug is excreted in the urine (Stecklair et al., 2001), but data are lacking for birds. When given to laying hens at low doses in the feed, halofuginone residues are not detectable in eggs, but as dosage increases, residues appear and can persist for days to weeks, depending on the concentration given (Yakkundi et al., 2002; Mortier et al., 2005; Mulder et al., 2005) (Table 11). Residues occur at similar levels in egg yolk and albumen, in contrast to many drugs reviewed here (Yakkundi et al., 2002), although residues are more persistent in yolk (Mortier et al., 2005).

Meticlorpindol, also called clopidol, is a coccidiostatic pyridinol (Botsoglou & Fletouris, 2001). There are few data on the metabolism of meticlorpindol in poultry, but it has been shown that in chickens the compound is absorbed from the GI tract to a significant extent (McQuistion & McDougald, 1979) and distributed widely to tissues (Pang et al., 2001), but is not extensively metabolized (Smith, 1969). In rabbits, orally administered meticlorpindol is rapidly absorbed and excreted almost completely in urine (Cameron et al., 1975). Meticlorpindol fed to laying hens is deposited in egg albumen at concentrations about twice that found in egg yolk (Mattern et al., 1990), and residues can persist for several weeks when the medication is given at high doses (Hafez et al., 1988; Mattern et al., 1990) (Table 11).

Ectoparasiticides

While ectoparasites rarely cause mortality in poultry, the physical stress associated with infestations can result in decreased production and economic losses (Axtell & Arends, 1990). Some ectoparasites can also be vectors of disease (Shah et al., 2004; Moro et al., 2009). Common poultry parasites include the northern fowl mite (Ornithonyssus sylviarum and Ornithonyssus bursa), the chicken body louse (Menacanthus stramineus), the chicken mite (Dermanyssus gallinae), the bedbug (Cimes lectularius) and various tick species (Axtell & Arends, 1990; Shah et al., 2004). The primary methods of control of poultry ectoparasites are spraying insecticides on the birds themselves, or treating the environment and removing used or contaminated litter. Classes of ectoparasiticides commonly used in the poultry industry include the carbamates, organophosphates, and pyrethrins. Although they are generally applied topically, most ectoparasiticides can be absorbed through the skin and have toxic effects (Al-Saleh, 1994).

Carbamates.  Carbamates (e.g. carbaryl, propoxur) are reversible acetylcholinesterase inhibitors derived from a toxic substance found in Calabar beans, the seeds of Physostigma venenosum (Blagburn & Lindsay, 2001). Some carbamates are used to treat ticks, mites, and lice in poultry and livestock (Blagburn & Lindsay, 2001).

Orally administered carbamates are well absorbed from the GI tract in chickens and widely distributed to tissues (Hicks et al., 1970). The major pathway of excretion is via the urine, but eggs laid during and after treatment also contain low-level residues (Paulson et al., 1972). Carbamate residues occur in both egg yolk and albumen, but are more persistent in yolk (Paulson & Feil, 1969; Andrawes et al., 1972) (Table 12). Following topical administration, available data suggest that carbamates can be absorbed and metabolized to a significant degree, and long-lasting residues occur in eggs (Table 12) (Ivey et al., 1984).

Table 12.   Residues of ectoparasiticides in eggs following treatment of laying hens
EctoparasiticsApproval status (laying hens)*Tolerance/maximum residue limitAnalytical methodLimit of detectionLimit of quantificationRouteDoseHen age (months)Treatment duration (days)Days from last treatment until residues no longer detectedSource
  1. Y, yolk; A, albumen; WE, whole egg; *see Appendix for list of definitions and abbreviations; tolerance levels for pesticides in foods are set in the USA by the Environmental Protection Agency. EU maximum residue limits for pesticides in eggs are taken from the Council of the European Economic Community’s directives 76/895/EEC, 86/362/EEC, 86/363/EEC and 90/642/EEC; N/A: The US FDA does not issue approvals for pesticides; §prepared from a commercial 80% carbaryl wettable powder; treatments were 4 days apart; **a commercially available propoxur solution (0.5–1%) was used; ††treatments were 7 days apart; ‡‡< 5; §§a commercially available 50% phoxim solution was used to prepare treatments; ¶¶three formulations of encapsulated tetrachlorvinphos were used: a 93% formulation (100, 400 and 800 mg/kg feed); a 60% formulation (50, 100, 200, 400 and 800 mg/kg feed); and a 52% formulation (50 and 100 mg/kg feed). Residues were only detected in eggs of hens fed the 93% formulation at 800 mg/kg feed; ***a 75% powder was used to prepare treatments; †††prepared from a commercial 50% powder; ‡‡‡the 0.5% P32-malathion solution was prepared from a concentrated solution of 57% P32-malathion, 32% xylene and 11% Triton X-100; §§§no data available between days 7 and 14; ¶¶¶a commercial 50% oral drench powder was used.

CarbarylEU: not approved; USA: N/ANoneColorimetric0.1 mg/kgNS*Feed200 mg/kg feed187Y: 0; A: 0McCay and Arthur (1962)
LSC* & LC*NS5.0 mg/kgOral (Capsule)7 mg/kg feed equivalent631Y: >6; A: 1; WE: 6Andrawes et al. (1972)
21 mg/kg feed equivalent631Y: >6; A: 1; WE: >6
70 mg/kg feed equivalent631Y: >7; A: 2
8.7 mg/day (70 mg/kg feed equivalent)124Y: >7; A: 2; WE: >7
LSC*NSNSOral (Capsule)10 mg/kg bw*NS1Y: >12; A: >12; WE: >12Paulson and Feil (1969)
GC*0.01 mg/kgNSDip0.5% solution§141WE: 55Ivey et al. (1984)
1.0% solution§141WE: >56
Colorimetric0.2 mg/kgNSDust4 g 5% dust/henNS3WE: 0Johnson et al. (1963)
PropoxurEU: not approved; USA: N/AEU: 0.05 mg/kgLC-DAD*2 μg/kg5 μg/kgHenhouse sprayed10 g/L**NS3††WE: >25Hamscher et al. (2003)
PermethrinEU: not approved; USA: N/AEU: 0.05 mg/kg; USA: 0.1 mg/kgLSC0.1 μg/kgNSSpray3.77 mg/bird71Y: 27; A: 2Hunt et al. (1979)
11.94 mg/bird71Y: 48; A: 6 
GC2 μg/kgNS20 mg/bird71Y: >21; A: 0Braun et al. (1981)
TLC*10 μg/kgNSOral (capsule)10 mg/kg bwNS3Y: >9; A: 6Gaughan et al. (1978)
DeltamethrinEU: not approved; USA: N/AEU: 0.05 mg/kg; USA: 0.02 mg/kgLSC & GC-MS*5 μg/kgNSFeed7.5 mg/bird133Y: >5; A: 5Akhtar et al. (1985)
GC10 μg/kgNSOral (stomach tube)10 mg/kg bwNS1Y: >10; A: 10Saleh et al. (1986)
CypermethrinEU: not approved; USA: N/AEU: 0.05 mg/kgGC10 μg/kgNSOral (stomach tube)10 mg/kg bwNS1Y: >10; A: 10Saleh et al. (1986)
LSC5 μg/kgNSFeed3.1–6.1 mg/kg bw123Y: >11Akhtar et al. (1987)
FenvalerateEU: not approved; USA: N/AEU: 0.02 mg/kgGC10 μg/kgNSOral (stomach tube)10 mg/kgNS1Y: >10; A: 10Saleh et al. (1986)
LSC, TLC & GC0.06 μg/gNSOral (gavage)7.5 mg/kg bw124Y: >6; A: 6Akhtar et al. (1989)
LSC & GLC*0.02 μg/gNSFeed9.2 mg/kg feed1249WE: 8Boyer et al. (1992)
FluvalinateEU: not approved; USA: N/ANoneLSC & LCNSNSOral (capsule)0.1 mg/kgNS1Y: 9‡‡Staiger et al. (1982)
1 mg/kg bwNS1Y: 12; A: 3‡‡
10 mg/kg bwNS1Y: 13‡‡
100 mg/kg bwNS1Y: 13‡‡
PhoximEU: approved; USA: N/AEU: 60 μg/kgHPLC*2 μg/kg5 μg/kgHenhouse sprayed0.2% solution§§NS1WE: >25Hamscher et al. (2007)
Henhouse sprayed0.2% solution§§NS2††WE: >25
TetrachlorvinphosEU: not approved; US: N/AUS: 0.2 mg/kgGC0.001 mg/kgNSFeed50 mg/kg feed¶¶NS14Y: 0Wasti and Shaw (1971)
100 mg/kg feed¶¶NS14Y: 0
200 mg/kg feed¶¶NS14Y: 0
400 mg/kg feed¶¶NS14Y: 0
800 mg/kg feed¶¶NS14Y: 1
GLC0.02 mg/kgNS400 mg/kg feed9364Y: 0; A: 0Sherman and Herrick (1971)
800 mg/kg feed9364Y: 0; A: 0
LSC & GC-MS0.01 mg/kgNS50 mg/kg feed & 450 μg P.O. (capsule)187WE: >7Akhtar and Foster (1981)
GC0.008 mg/kgNSP.O. (Gavage)25 mg/kg*** bwNS7Y: 1Yadava and Shaw (1970)
50 mg/kg*** bwNS7Y: 2
100 mg/kg*** bwNS7Y: 3
200 mg/kg*** bwNS7Y: >7
GC0.004 mg/kgNSDip0.5% suspension†††141WE: 20Ivey et al. (1982)
1.0% suspension†††141WE: 14
GCY: 0.02; A: 0.01 mg/kgNSHenhouse sprayed0.5 g/m2***NS1WE: 1Pitois et al. (1973a)
1 g/m2***1WE: 7
GC0.002 mg/kgNSDust bath boxes or litter treated450 g 3% dust for 20 birdsNS28Y: 0; A: 20Ivey et al. (1969)
45 g 75% powder for 20 birdsNS28Y: 13; A: 34
ChlorpyrifosEU: not approved; USA: N/A0.01 mg/kg (EU & USA)Potentiometric0.2 mg/kgNSOral32 mg/kg bw91WE: >21Abbassy et al. (1981)
PirimiphosmethylEU: not approved; USA: N/AEU: 0.05 mg/kgPotentiometric0.2 mg/kgNSOral35 mg/kg bw91WE: >21Abbassy et al. (1981)
DichlofenthionEU: not approved; USA: N/ANoneGLCY: 19 μg/kg; A: 86 μg/kgNSFeed50 mg/kg feed755 weeksY: 0Sherman et al. (1972)
100 mg/kg feed755 weeksY: 5
200 mg/kg feed755 weeksY: 10
800 mg/kg feed755 weeksY: 10
MalathionEU: not approved; USA: N/AUSA: 0.1 mg/kgRadioassay0.01 mg/kgNSFeed100 mg/kg8–915Y: >9; A: >9; WE: >9March et al. (1956)
Birds sprayed38 mL of 0.5% solution‡‡‡ (190 mg/bird)8–91Y: >30
CoumaphosEU: not approved; USA: N/ANoneRadioassay0.02 mg/kgNSBirds dusted50 mg/kg bw181Y: 10; A: 10Dorough et al. (1961)
50 mg/kg bw182Y: >12; A: 10
Fluorometric0.02 mg/kgNSHenhouse dusted5% dust, 2 oz/30 ft2 floor spaceNS1Y: 0Shaw et al. (1964)
Henhouse fogged25% suspension, 2 oz/30 ft2 floor spaceNS1Y: 14§§§
Oral (capsule)0.5 mg/kg bw¶¶¶NS7–10Y: 0
1 mg/kg bw¶¶¶NS7–10Y: 0
5 mg/kg bw¶¶¶NS7–10Y: > 16‡‡

Pyrethrins and pyrethroids.  Pyrethrins are a group of insecticides derived from the pyrethrum flower (Chrysanthemum cinerariaefolium); synthetic forms based on the naturally occurring compounds are called pyrethroids (Blagburn & Lindsay, 2001). Pyrethrins and pyrethroids are among the least toxic of the insecticides and are not as well absorbed through skin as other insecticidal compounds (Al-Saleh, 1994). In general, pyrethrins and pyrethroids are effective against mites, fleas, flies, lice and ticks (Blagburn & Lindsay, 2001). In poultry, permethrin is the primary pyrethroid used to treat ectoparasite infections, and especially infestations of the northern fowl mite, which has developed resistance to many other insecticides (Axtell & Arends, 1990). Other pyrethroids commonly used include deltamethrin, cypermethrin and fenvalerate.

Pyrethroids are most often administered to poultry topically, as a spray or dust (Bishop, 2001). When topically applied, pyrethroids are absorbed and widely distributed to tissues, but concentrate particularly in fat and skin (Hunt et al., 1979; Braun et al., 1981; Heitzman, 1997, 2000). Residues in skin and fat are very persistent, as are residues in the egg yolk (Hunt et al., 1979; Braun et al., 1981) (Table 12).

In chickens, orally administered pyrethroids are widely distributed to tissues and extensively metabolized, with the highest residue concentrations occurring in the kidney, liver and fat (Gaughan et al., 1978; Akhtar et al., 1985, 1987, 1989; Hutson & Stoydin, 1987). Residues are found in egg albumen at low levels, and in egg yolks at similar concentrations to those found in kidney and liver for several days following oral dosing (Gaughan et al., 1978; Akhtar et al., 1985, 1989).

Organophosphates.  Organophosphate insecticides (e.g. phoxim, coumaphos, tetrachlorvinphos, malathion) are potent acetylcholinesterase inhibitors that are applied to poultry houses or individual birds to treat infestations of lice, mites and ticks (Axtell & Arends, 1990; Blagburn & Lindsay, 2001). In chickens and other animals, organphosphates can be absorbed through the skin as well as through the mucous membranes of the eyes, respiratory tract and digestive system (Gupta & Paul, 1977; Abou-Donia et al., 1982; Al-Saleh, 1994). Following absorption, organophosphates are extensively metabolized and distributed widely to tissues, and residues can be found in muscle, fat, internal organs and skin as well as eggs (March et al., 1956; Ivey et al., 1969; Yadava & Shaw, 1970; Sherman & Herrick, 1971; Pitois et al., 1973b; Gupta & Paul, 1977; Akhtar & Foster, 1981). While in chickens the majority of an organophosphate dose is generally eliminated in a few days, detectable residues can persist in tissues and eggs for several weeks (March et al., 1956; Dorough et al., 1961) (Table 12). The limited available data suggest that in chickens elimination occurs primarily via the urine (Gupta & Paul, 1977). Tetrachlorvinphos residues appear to be more persistent in egg albumen than in yolk (Ivey et al., 1969; Pitois et al., 1973a), while the opposite may be true for coumaphos (Dorough et al., 1961).

Conclusions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Overview of the drug classes
  5. Conclusions
  6. Acknowledgements
  7. References
  8. Appendix

There are a large number of studies describing drug deposition and depletion from chicken eggs, but these are scattered throughout the primary literature. In this review, these data are compiled for easy reference to aid understanding and draw attention to the often overlooked issue of veterinary drug residues in eggs. It is important to note that laying hens deposit veterinary drugs from a wide variety of drug classes into their eggs, and residues can persist for some time after treatment has ended.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Overview of the drug classes
  5. Conclusions
  6. Acknowledgements
  7. References
  8. Appendix

The authors thank Ellen Guttadauro for her talents in biological illustration.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Overview of the drug classes
  5. Conclusions
  6. Acknowledgements
  7. References
  8. Appendix
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Appendix

  1. Top of page
  2. Abstract
  3. Introduction
  4. Overview of the drug classes
  5. Conclusions
  6. Acknowledgements
  7. References
  8. Appendix

Definitions and abbreviations

Approval statusApproval by the Food and Drug Administration (USA) or the European Commission (EU).
Tolerance/maximum residue limit‘Tolerance’ refers to the maximum drug residue level established by the U.S. Food and Drug Administration that is allowed for a particular drug in a given food product. ‘Maximum residue limit’ is the equivalent term for maximum allowable drug residue levels established by the European Commission (EC regulation 37/2010).
ASTED-LCAutomated sequential trace enrichment dialysis liquid chromatography
bwBody weight
CF-LCContinuous flow liquid chromatography
ELISAEnzyme-linked immunosorbent assay
GCGas chromatography
GC-MSGas chromatography-mass spectrometry
GLCGas-liquid chromatography
HPLCHigh-performance liquid chromatography
HPLC-MS (-MS/MS)High-performance liquid chromatography-mass spectrometry (or tandem mass spectrometry)
HPTLCHigh-performance thin-layer chromatography
ICIntra-cardiac
IMIntramuscular
LCLiquid chromatography
LC-APCI-MSLiquid chromatography-atmospheric pressure chemical ionization mass spectrometry
LC-DADLiquid chromatography-diode array detection
LC-ES-MS/MSLiquid chromatography-electrospray-tandem mass spectrometry.
LC-MS (-MS/MS)Liquid chromatography-mass spectrometry (or tandem mass spectrometry)
LSCLiquid scintillation counter (used to quantify radio-labelled drug)
NSNot specified
PLE, LC-FLDPressurized liquid extraction and liquid chromatography with fluorescence detection.
RIARadioimmunoassay
SCSubcutaneous
TLCThin-layer chromatography