ANTIBIOTICS CHEMICAL HAZARDS BY ASHOK SIR

Antibiotics – Chemical Hazard

Ashok Kumar K

Raw materials -- ingredients, packaging Raw materials -- ingredients, packaging material, water -- may be sources of material, water -- may be sources of hazardshazards

Knowledge concerning the likelihood of Knowledge concerning the likelihood of the presence of hazards in raw materials the presence of hazards in raw materials is the basis of any HACCP systemis the basis of any HACCP system

This knowledge is used to identify This knowledge is used to identify potential hazards and decide whether potential hazards and decide whether they need to be controlledthey need to be controlled

• The amount of the chemical may determine whether it is a hazard or not.

• Some may require exposure over prolonged periods to have a toxic effect.

• Regulatory limits are set for some of those contaminants.

• Chemical hazards can be separated into three categories:

• Naturally occurring chemicals.

• Intentionally added chemicals.

• Unintenionally or incidentially added chemicals

Chemical Hazards

Unintentionally or Incidentially Added Chemicals:

Chemicals can become part of a food without being intentionally added.

These incidental chemicals might already be in a food ingredient when it is received.

For example, certain seafood may contain small but legal residues of approved antibiotics.

Packaging materials that are in direct contact with ingredients or the product can be a source of incidental chemicals, such as sanitizers or inks.

Most incidental chemicals have no effect on food safety, and others are only a concern if they are present in too high an amount.

Unintentionally or Incidentially Added Chemicals:

Incidental chemicals also include accidental additions of prohibited substances such as poisons or insecticides that may not be allowed at any level.

• Agricultural chemicals (e.g., pesticides, fungicides, herbicides, fertilizers, antibiotics and growth hormones)

• Prohibited substances (Code of Federal Regulations, Chapter 21, Section 189)

• Toxic elements and compounds (e.g., lead, zinc, arsenic, mercury, cyanide)

• Secondary direct and indirect - Plant chemicals (e.g.,lubricants, cleaning

compounds, sanitizers, paint)

Antibiotic/AntimicrobialAntibiotic/Antimicrobial

AntibioticAntibiotic: Chemical : Chemical produced produced by a microorganismby a microorganism that kills that kills or inhibits the growth of or inhibits the growth of another microorganismanother microorganism

Antimicrobial agentAntimicrobial agent: Chemical : Chemical that kills or inhibits the that kills or inhibits the growth of microorganismsgrowth of microorganisms

Ehrlich’s Magic Bullets Ehrlich’s Magic Bullets

Fleming and PenicillinFleming and Penicillin

ChemotherapyChemotherapy

The use of drugs to treat a diseaseThe use of drugs to treat a disease

Selective toxicitySelective toxicity: A drug that kills : A drug that kills harmful microbes without damaging harmful microbes without damaging the hostthe host

MECHANISMS OF ACTION OF MECHANISMS OF ACTION OF ANTIBACTERIAL DRUGSANTIBACTERIAL DRUGS

Mechanism of action Mechanism of action include:include: Inhibition of cell wall Inhibition of cell wall

synthesissynthesis Inhibition of protein Inhibition of protein

synthesissynthesis Inhibition of nucleic acid Inhibition of nucleic acid

synthesissynthesis Inhibition of metabolic Inhibition of metabolic

pathwayspathways Interference with cell Interference with cell

membrane integritymembrane integrity


Inhibition of Cell wall synthesisInhibition of Cell wall synthesis Bacteria cell wall unique in Bacteria cell wall unique in

constructionconstruction Contains peptidoglycanContains peptidoglycan

Antimicrobials that interfere with Antimicrobials that interfere with the synthesis of cell wall do not the synthesis of cell wall do not interfere with eukaryotic cellinterfere with eukaryotic cell

Due to the lack of cell wall in animal Due to the lack of cell wall in animal cells and differences in cell wall in cells and differences in cell wall in plant cellsplant cells

These drugs have very high These drugs have very high therapeutic indextherapeutic index

Low toxicity with high effectivenessLow toxicity with high effectiveness Antimicrobials of this class includeAntimicrobials of this class include

ββ lactam drugs lactam drugs Vancomycin Vancomycin BacitracinBacitracin


Penicillins and Penicillins and cephalosporins cephalosporins Part of group of drugs Part of group of drugs

called called ββ –lactams –lactams Have shared chemical Have shared chemical

structure called structure called ββ-lactam -lactam ringring

Competitively inhibits Competitively inhibits function of penicillin-function of penicillin-binding proteinsbinding proteins

Inhibits peptide bridge Inhibits peptide bridge formation between glycan formation between glycan moleculesmolecules

This causes the cell wall to This causes the cell wall to develop weak points at the develop weak points at the growth sites and become growth sites and become fragile.fragile.


The weakness in the The weakness in the cell wall causes the cell wall causes the cell to lyze.cell to lyze.


The weakness in the cell wall The weakness in the cell wall causes the cell to lyze.causes the cell to lyze.

Penicillins and cephalosporins Penicillins and cephalosporins are considered bactericidal. are considered bactericidal.

Penicillins are more effective Penicillins are more effective against Gram+ bacteria. This against Gram+ bacteria. This is because Gram + bacteria is because Gram + bacteria have penicillin binding have penicillin binding proteins on their walls.proteins on their walls.

Inhibition of protein synthesisInhibition of protein synthesis Structure of prokaryotic ribosome acts as target for Structure of prokaryotic ribosome acts as target for

many antimicrobials of this classmany antimicrobials of this class Differences in prokaryotic and eukaryotic ribosomes Differences in prokaryotic and eukaryotic ribosomes

responsible for selective toxicityresponsible for selective toxicity Drugs of this class includeDrugs of this class include

AminoglycosidesAminoglycosides TetracyclinsTetracyclins MacrolidsMacrolids ChloramphenicolChloramphenicol



AminoglycosidesAminoglycosides Irreversibly binds to 30S Irreversibly binds to 30S

ribosomal subunitribosomal subunit Causes distortion and Causes distortion and

malfunction of ribosomemalfunction of ribosome Blocks initiation Blocks initiation

translationtranslation Causes misreading of Causes misreading of

mRNAmRNA Not effective against Not effective against

anaerobes, enterococci anaerobes, enterococci and streptococciand streptococci

Often used in synergistic Often used in synergistic combination with combination with ββ-lactam -lactam drugsdrugs

Allows aminoglycosides to Allows aminoglycosides to enter cells that are often enter cells that are often resistantresistant


Examples of Examples of aminoglycosides aminoglycosides includeinclude

Gentamicin, Gentamicin, streptomycin and streptomycin and tobramycin tobramycin

Side effects with Side effects with extended use includeextended use include

Otto toxicityOtto toxicity NephrotoxicityNephrotoxicity


TetracyclinsTetracyclins Reversibly bind 30S ribosomal Reversibly bind 30S ribosomal

subunitsubunit Blocks attachment of tRNA to Blocks attachment of tRNA to

ribosomeribosome Prevents continuation of Prevents continuation of

protein synthesisprotein synthesis

Effective against certain Gram Effective against certain Gram + and Gram -+ and Gram -

Newer tetracyclines such as Newer tetracyclines such as doxycycline have longer half-doxycycline have longer half-lifelife

Allows for less frequent dosingAllows for less frequent dosing Resistance due to decreased Resistance due to decreased

accumulation by bacterial cellsaccumulation by bacterial cells Can cause discoloration of Can cause discoloration of

teeth if taken as young childteeth if taken as young child


Resistance due to Resistance due to decreased decreased accumulation by accumulation by bacterial cellsbacterial cells

Can cause discoloration Can cause discoloration of teeth if taken as of teeth if taken as young childyoung child


MacrolidesMacrolides Reversibly binds to 50S Reversibly binds to 50S

ribosomeribosome Prevents continuation of Prevents continuation of

protein synthesisprotein synthesis Effective against variety of Effective against variety of

Gram + organisms and Gram + organisms and those responsible for those responsible for atypical pneumoniaatypical pneumonia

Often drug of choice for Often drug of choice for patients allergic to patients allergic to penicillinpenicillin

Macrolids includeMacrolids include Erythromycin, Erythromycin,

clarithromycin and clarithromycin and azithromycinazithromycin


ChloramphenicolChloramphenicol Binds to 50S ribosomal Binds to 50S ribosomal

subunitsubunit Prevents peptide bonds Prevents peptide bonds

from forming and from forming and blocking proteins blocking proteins synthesissynthesis

Effective against a wide Effective against a wide variety of organismsvariety of organisms

Generally used as drug Generally used as drug of last resort for life-of last resort for life-threatening infectionsthreatening infections

Rare but lethal side Rare but lethal side effect is aplastic anemiaeffect is aplastic anemia

Inhibition of nucleic acid synthesisInhibition of nucleic acid synthesis These includeThese include

FluoroquinolonesFluoroquinolones Rifamycins Rifamycins


FluoroquinolonesFluoroquinolones Inhibit action of topoisomerase DNA Inhibit action of topoisomerase DNA

gyrasegyrase Topoisomerase maintains supercoiling of DNATopoisomerase maintains supercoiling of DNA

Effective against Gram + and Gram -Effective against Gram + and Gram - Examples includeExamples include

Ciprofloxacin and ofloxacinCiprofloxacin and ofloxacin Resistance due to alteration of DNA Resistance due to alteration of DNA

gyrasegyrase


RifamycinsRifamycins Block prokaryotic RNA polymeraseBlock prokaryotic RNA polymerase

Block initiation of transcriptionBlock initiation of transcription Rifampin most widely used rifamycinsRifampin most widely used rifamycins Effective against many Gram + and some Gram - as well Effective against many Gram + and some Gram - as well

as members of genus as members of genus MycobacteriumMycobacterium Primarily used to treat tuberculosis and Hansen’s Primarily used to treat tuberculosis and Hansen’s

disease as well as preventing meningitis after exposure disease as well as preventing meningitis after exposure to to N. meningitidisN. meningitidis

Resistance due to mutation coding RNA polymeraseResistance due to mutation coding RNA polymerase Resistance develops rapidlyResistance develops rapidly



Inhibition of metabolic Inhibition of metabolic pathwayspathways Relatively fewRelatively few Most useful are folate Most useful are folate

inhibitorsinhibitors Mode of actions to Mode of actions to

inhibit the production inhibit the production of folic acidof folic acid

Antimicrobials in this Antimicrobials in this class includeclass include

SulfonamidesSulfonamides Trimethoprim Trimethoprim


SulfonamidesSulfonamides Group of related compoundsGroup of related compounds

Collectively called sulfa drugsCollectively called sulfa drugs Inhibit growth of Gram + and Gram - organismsInhibit growth of Gram + and Gram - organisms

Through competitive inhibition of enzyme that aids in Through competitive inhibition of enzyme that aids in production of folic acidproduction of folic acid

Structurally similar to para-aminobenzoic acidStructurally similar to para-aminobenzoic acid Substrate in folic acid pathwaySubstrate in folic acid pathway

Human cells lack specific enzyme in folic acid pathwayHuman cells lack specific enzyme in folic acid pathway Basis for selective toxicityBasis for selective toxicity

Resistance due to plasmidResistance due to plasmid Plasmid codes for enzyme that has lower affinity to drugPlasmid codes for enzyme that has lower affinity to drug

TrimethoprimTrimethoprim Inhibits folic acid productionInhibits folic acid production

Interferes with activity of enzyme following Interferes with activity of enzyme following enzyme inhibited by sulfonamidesenzyme inhibited by sulfonamides

Often used synergistically with sulfonamideOften used synergistically with sulfonamide Most common mechanism of resistance is Most common mechanism of resistance is

plasmid encoded alternative enzymeplasmid encoded alternative enzyme Genes encoding resistant to sulfonamide and Genes encoding resistant to sulfonamide and

trimethoprim are often carried on same plasmidtrimethoprim are often carried on same plasmid



Interference with cell Interference with cell membrane integritymembrane integrity Few damage cell Few damage cell

membranemembrane Polymixn B most commonPolymixn B most common

Common ingredient in Common ingredient in first-aid skin ointmentsfirst-aid skin ointments

Binds membrane of Gram - Binds membrane of Gram - cellscells

Alters permeabilityAlters permeability Leads to leakage of cell Leads to leakage of cell

and cell deathand cell death Also bind eukaryotic cells Also bind eukaryotic cells

but to lesser extentbut to lesser extent Limits use to topical Limits use to topical

applicationapplication

The feeding of antibiotics is associated with decreases in animal gut mass, increased intestinal absorption of nutrients and energy sparing.

This results in a reduction in the nutrient cost for maintenance, so that a larger portion of consumed nutrients can be used for growth and production, thereby improving the efficiency of nutrient use.

Antibiotics act by eliminating the subclinical population of pathogenic microorganisms.

Eradicating this metabolic drain allows more efficient use of nutrientsfor food production.

Antibiotics alter the non-pathogenic intestinal flora, producing beneficial effects on digestive processes and more efficient utilization of nutrients in feeds.

Antibiotics as growth promoters

It has been estimated that around 6 percent of the energy in a pig’s diet could be lost due to microbial fermentation occurring in the stomach and small intestine.

Intestinal bacteria inactivate pancreatic enzymes and metabolize dietary protein with the production of ammonia and biogenic amines.

Antibiotics inhibit these activities and increase the digestibility of dietary protein.

Experimental results obtained with some antibiotics commonly used as growth promoters (chlortetracycline, penicillin and sulfamethazine) have shown that treated pigs have higher serum levels of an insulin-like growth factor.

(Committee on Drug Use in Food Animals, 1999; Doyle, 2001).

Antibiotics as growth promoters

EU legislation on residuesEU legislation on residues

Residue DefinitionResidue Definition

Residues of veterinary medicinal productsResidues of veterinary medicinal productsmeans all pharmacologically active means all pharmacologically active substances, whether active principles, substances, whether active principles, excipients or degradation products, and their excipients or degradation products, and their metabolites which remain in foodstuffs metabolites which remain in foodstuffs obtained from animals to which the veterinary obtained from animals to which the veterinary medicinal product in question has been medicinal product in question has been administered; administered;

Regulation EEC 2377/90 Regulation EEC 2377/90

Maximum Residue LimitMaximum Residue Limit

means the maximum concentration means the maximum concentration of residue resulting from the use of of residue resulting from the use of an approved veterinary medicinal an approved veterinary medicinal product which may be accepted by product which may be accepted by the Community to be legally the Community to be legally permitted or recognized as permitted or recognized as acceptable in or on a food acceptable in or on a food

Regulation EEC 2377/90Regulation EEC 2377/90

The Limits The Limits

Regulation CEE 2377/90Regulation CEE 2377/90

define the European procedure for define the European procedure for the determination of the Maximum the determination of the Maximum Residue Limit (MRL) of veterinary Residue Limit (MRL) of veterinary drugs in animal origin foods drugs in animal origin foods

Necessary to know the fate a new Necessary to know the fate a new veterinary drug is in the final food. veterinary drug is in the final food.

ANNEX I ANNEX I List of pharmacologically active List of pharmacologically active substances for which maximum substances for which maximum residue levels have been fixed residue levels have been fixed

ANNEX II ANNEX II List of substances not subject to List of substances not subject to maximum residue levels maximum residue levels

ANNEX III ANNEX III List of pharmacologically active List of pharmacologically active substances used in veterinary substances used in veterinary medicinal products for which maximum medicinal products for which maximum residue levels have been fixedresidue levels have been fixed

ANNEX IV ANNEX IV Lists of pharmacologically active Lists of pharmacologically active substances for which no maximum substances for which no maximum levels can be fixedlevels can be fixed

ANNEX IVANNEX IV

AristolochiaAristolochia sppspp. and its preparation . and its preparation ChloramphenicolChloramphenicol ChloroformChloroformChloropromazine Chloropromazine Colchicine Colchicine DapsoneDapsoneDimetridazole Dimetridazole Metronidazole Metronidazole NitrofuransNitrofurans (furazolidone included) (furazolidone included)RonidazoleRonidazole

Official ControlOfficial Control

Council Directive 96/23/EC Council Directive 96/23/EC

Council Directive 96/23/EC on measures Council Directive 96/23/EC on measures to monitor certain substances and to monitor certain substances and residues thereof in live animals and residues thereof in live animals and animal products and repealing Directives animal products and repealing Directives 85/358/EEC and 86/469/EEC and 85/358/EEC and 86/469/EEC and Decisions 89/187/EEC and 91/664/EECDecisions 89/187/EEC and 91/664/EEC

Council Directive Council Directive 96/23/EC96/23/EC

Guidelines for residues control in Guidelines for residues control in animals and in their productsanimals and in their products

detailed procedures to set up a detailed procedures to set up a National monitoring plan; National monitoring plan;

detail on sampling procedures; detail on sampling procedures; any type of animal or food have a any type of animal or food have a

definite set of categories definite set of categories substance that must be monitored.substance that must be monitored.

Definitions Definitions Directive 96/23/ECDirective 96/23/EC

unauthorized substances or productsunauthorized substances or products: : shall mean substances or products the administering shall mean substances or products the administering of which to animals is of which to animals is prohibitedprohibited under Community under Community legislation; legislation;

illegal treatmentillegal treatment: shall mean:: shall mean:

the use of unauthorized substances or products the use of unauthorized substances or products or or

the use of substances or products authorized under the use of substances or products authorized under Community legislation for purposes or under Community legislation for purposes or under conditions other than those laid down in Community conditions other than those laid down in Community legislation or, where appropriate, in the various legislation or, where appropriate, in the various national legislationsnational legislations

GROUP A GROUP A Substances having anabolic effect and Substances having anabolic effect and

unauthorized substancesunauthorized substances (1) Stilbenes, stilbene derivatives, (1) Stilbenes, stilbene derivatives,

and their salts and estersand their salts and esters(2) Antithyroid agents(2) Antithyroid agents(3) Steroids(3) Steroids(4) Resorcylic acid lactones including zeranol(4) Resorcylic acid lactones including zeranol(5) Beta-agonists(5) Beta-agonists

(6) Compounds included in Annex IV to Council (6) Compounds included in Annex IV to Council Regulation (EEC) No 2377/90 Regulation (EEC) No 2377/90

Horm

ones and grow

promoters

GROUP BGROUP BVeterinary drugs and contaminantsVeterinary drugs and contaminants

(1)(1) Antibacterial substances, including sulphonomides, Antibacterial substances, including sulphonomides, quinolonesquinolones

(2)(2) Other veterinary drugsOther veterinary drugs(a) Anthelmintics(a) Anthelmintics(b) Anticoccidials, including nitroimidazoles(b) Anticoccidials, including nitroimidazoles(c) Carbamates and pyrethroids(c) Carbamates and pyrethroids(d) Sedatives(d) Sedatives(e) Non-steroidal anti-inflammatory drugs (NSAIDs)(e) Non-steroidal anti-inflammatory drugs (NSAIDs)(f) Other pharmacologically active substances(f) Other pharmacologically active substances

(3)(3) Other substances and environmental contaminantsOther substances and environmental contaminants(a) Organochlorine compounds including PCBs(a) Organochlorine compounds including PCBs(b) Organophosphorus compounds(b) Organophosphorus compounds(d) Chemical elements(d) Chemical elements(d) Mycotoxins(d) Mycotoxins(e) Dyes(e) Dyes(f) Others (f) Others

Group A / B Group A / B Two Different WorldsTwo Different Worlds

Different sampling proceduresDifferent sampling procedures Different analytical methods (Different analytical methods (LC-MS/MSLC-MS/MS)) Different tolerance (Different tolerance (zero tolerancezero tolerance)) Different penalties Different penalties

c

Group A Group B

Chloramphenicol Nitrofurans

Approved Vet Drugs

Environment contaminants

Residue of authorised drugsResidue of authorised drugs

Evaluation of the observance of the Evaluation of the observance of the Maximum Residue Limit (MRL) Maximum Residue Limit (MRL)

Definition of Action LimitDefinition of Action Limit

Safety for the consumer Safety for the consumer Reliability of analytical Reliability of analytical

techniques used. techniques used. Knowledge of metabolism or Knowledge of metabolism or

distribution kinetics. distribution kinetics.

For the forbidden drugs or For the forbidden drugs or not authorised substances not authorised substances

a limit of action doesn't a limit of action doesn't correspond in any case to correspond in any case to

authorise its useauthorise its use

General limitsGeneral limits

In many countries a general limit In many countries a general limit exist , and is used when no limits exist , and is used when no limits are defined.are defined.

This limit is generally 0,01 mg/kg This limit is generally 0,01 mg/kg (10 ppb), close to a generic (10 ppb), close to a generic (old)(old) instrumental detection limits.`instrumental detection limits.`

Residue of not authorised drugs (Group B - no toxic)

• These limits are specified in the National Residues Monitoring Plan.

• There aren’t a uniform criteria for to define limits for this type of residue.

• The limit of detection of the analytical methods are often used.

Residue of forbidden drugsResidue of forbidden drugs(Group A)(Group A)

Zero tolerance Zero tolerance The action limit is generally fixed The action limit is generally fixed

at 1 ppb, at 1 ppb, Recently the EC request a very low Recently the EC request a very low

limit of detection (limit of detection (MRPL = 0,3 ppb for MRPL = 0,3 ppb for chloramphenicolchloramphenicol), ),

The limit in this context is The limit in this context is indicative, if a laboratory indicative, if a laboratory

have best performances in have best performances in terms of LoD, the sample terms of LoD, the sample

must be to considered must be to considered positivepositive

Commission Decision Commission Decision 2002/657/EC2002/657/EC

(12 August 2002)(12 August 2002)

Implementing Council Implementing Council Directive 96/23/EC Directive 96/23/EC concerning the performance concerning the performance of analytical methods and of analytical methods and the interpretation of resultsthe interpretation of results

Commission Decision 2002/657/EC (1)Commission Decision 2002/657/EC (1)

It is necessary to ensure the It is necessary to ensure the quality and quality and comparabilitycomparability of the of the analytical results generated by analytical results generated by laboratories approved for official laboratories approved for official residue control. residue control.

Commission Decision 2002/657/EC (2)Commission Decision 2002/657/EC (2)

It is necessary to determine It is necessary to determine common criteria for the common criteria for the interpretation of test resultsinterpretation of test results of of official control laboratories in official control laboratories in order to ensure a order to ensure a harmonisedharmonised implementation of Directive implementation of Directive 96/23/EC.96/23/EC.

Minimum Required Performance Minimum Required Performance LimitsLimits

It is necessary to provide for the It is necessary to provide for the progressive establishment of progressive establishment of Minimum Minimum Required Performance LimitsRequired Performance Limits ( (MRPLMRPL) of ) of analytical method for substances for which analytical method for substances for which no permitted limit has been established no permitted limit has been established and in particular for those substances and in particular for those substances whose whose use is not authoriseduse is not authorised, or is , or is specifically specifically prohibitedprohibited in the Community, in the Community, in order to ensure harmonised in order to ensure harmonised implementation of Directive 96/23/EC.implementation of Directive 96/23/EC.

Rapid Alert Rapid Alert SystemSystem

• Notification of a Notification of a directdirect or or indirectindirect risk risk to human health from food or feed.to human health from food or feed.• NetworkNetwork involving member states, involving member states, the Commission and the European the Commission and the European Food Safety Authority (EFSA).Food Safety Authority (EFSA).• The information from a member of The information from a member of the network shall be the network shall be immediatelyimmediately notified to the Commission and then notified to the Commission and then through the network.through the network.• The EFSA may supplement the The EFSA may supplement the notification with any scientific or notification with any scientific or technical information.technical information.

Regulation EC/178/2002Rapid Alert System

Exist three levels of information:Exist three levels of information:

1.1. Alert NotificationAlert Notification

2.2. Information NotificationInformation Notification

3.3. NewsNews

Levels of Information

• ConditionsConditions- Food on the market- Food on the market

- More than one Member State (MS)- More than one Member State (MS)

- Immediate action is required (real risk)- Immediate action is required (real risk)

• ActionsActions– Triggered by MS/EFSA (receive from Contact Triggered by MS/EFSA (receive from Contact

Points and evaluated by RASFF team in Points and evaluated by RASFF team in

SANCO)SANCO)

- Withdrawal of product from the market- Withdrawal of product from the market

Alert Notification

• Conditions: Conditions: - Not immediate action required- Not immediate action required

- Provide useful information- Provide useful information

• ActionsActions– No Actions is requiredNo Actions is required

Information Notification

• Conditions: Conditions:

- - Neither Alert nor InformationNeither Alert nor Information

• ActionsActions– No Actions is required No Actions is required

News

FLOW-CHART OF ACTIVITIES CARRIED OUT BY SANCO-RASFF

NEWS

MEMBER STATE NOTIFICATION

RASFF ASSESSMENT

FEEDBACK FROM MEMBER STATES

TRANSMISSION VIA CIRCA/E-MAIL

ELABORATION OF THE NOTIFICATION

INFORMATIONALERT

TRANSMISSION OF NOTIFICATIONS TO THETHIRD COUNTRIES CONCERNED

MEMBER STATES

COMMISSION SERVICES

E-MAILFAX

REPORTS/STATISTICS

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Table 2. Directive 96/23 list of substances Group A – Substances having anabolic effect and unauthorised substances (A1) Stilbenes, stilbene derivatives, and their salts and esters (A2) Antithyroid agents (A3) Steroids (A4) Resorcylic acid lactones including zeranol (A5) Beta-agonists (A6) Compounds included in Annex IV to Regulation (EEC) 2377/90 Group B – Vete rinary drugs†and contaminants (B1) Antibacterial substances, including sulphonamides, quinolones (B2) Other veterinary drugs (B2a) Anthelmintics (B2b) Anticoccidials, inc. nitroimidazoles (B2c) Carbamates and pyrethroids (B2d) Sedatives (B2e) Non-steroidal anti-inflammatory drugs (NSAIDs) (B2f) Other pharmacologically active substances (B3) Other substances and environmental contaminants (B3a) Organochlorine compounds including PcBs (B3b) Organophosphorus compounds (B3c) Chemical elements (B3d) Mycotoxins (B3e) Dyes (B3f) Others †Including unlicensed substances which could be used for veterinary purposes.

Antibiotics banned for animals intended for food production. Antibiotics banned for animals intended for food production.

Antibiotic Antibiotic Country Country Reason Reason Reference Reference

Spectinomycin Spectinomycin USA USA Its use is limited by Its use is limited by the ready development the ready development of bacterial resistance of bacterial resistance

USP, 2000d. USP, 2000d.

Enrofloxacin Enrofloxacin USA USA

Its use is limited by Its use is limited by the ready the ready development of development of bacterial bacterial resistance (quinolone) resistance (quinolone)

USP, 2000h. USP, 2000h.

Cloramphenicol Cloramphenicol Argentina, Canada, EU, Argentina, Canada, EU, Japan, USA, IndiaJapan, USA, India

Induces human Induces human aplastic aplastic anaemia anaemia

USP, 2000e; USP, 2000e; GESAMP, 1997; GESAMP, 1997; SANCO, 2001a. SANCO, 2001a.

NitrofuransNitrofuransArgentina, Canada, EU, Argentina, Canada, EU, Japan, USA,IndiaJapan, USA,India

Carcinogenicity and Carcinogenicity and mutagenictymutagenicty

USP, 2000e; USP, 2000e; GESAMP, 1997; GESAMP, 1997; SANCO, 2001aSANCO, 2001a

Rifampin Rifampin

Not labelled in USA or Not labelled in USA or Canada for use in animals, Canada for use in animals, including food-producing including food-producing animals animals

Tumorgenicity and Tumorgenicity and teratogenic effects on teratogenic effects on experimental animals experimental animals

USP, 2000k. USP, 2000k.

ANTIBIOTICS AUTHORIZED FOR USE IN AQUACULTURE ANTIBIOTICS AUTHORIZED FOR USE IN AQUACULTURE Antibiotic Antibiotic Treatment of Treatment of Reference Reference

Oxytetracycline Oxytetracycline (for medicated (for medicated feed) feed)

n Furunculosis in salmonids (salmon or trout) caused by AeromonasFurunculosis in salmonids (salmon or trout) caused by Aeromonasn Gafkemia in lobsters (caused by Aerococcus viridans). Gafkemia in lobsters (caused by Aerococcus viridans). n Hemorrhagic septicaemia due to Aeromonas hydrophila, A. sobria Hemorrhagic septicaemia due to Aeromonas hydrophila, A. sobria

and Pseudomonas. and Pseudomonas. n Cold water disease in salmonids, caused by Cytophaga Cold water disease in salmonids, caused by Cytophaga

psychrophilia. psychrophilia. n Columnaris disease in salmonids, caused by susceptible Columnaris disease in salmonids, caused by susceptible

Chondrococcus (Flexibacter) columnaris. Chondrococcus (Flexibacter) columnaris. n Enteric redmouth disease, caused by susceptible Yersinia ruckeri. Enteric redmouth disease, caused by susceptible Yersinia ruckeri. n Indicated for the control of Pseudomonas disease in catfish and Indicated for the control of Pseudomonas disease in catfish and

salmonids. salmonids. n Indicated for the control of ulcer disease caused by susceptible Indicated for the control of ulcer disease caused by susceptible

Haemophilus piscium in salmonids (salmon, trout).Haemophilus piscium in salmonids (salmon, trout).

USP, 2000g USP, 2000g

FlorfenicolFlorfenicolPremix Premix

Indicated in the treatment of furunculosis caused by susceptible Indicated in the treatment of furunculosis caused by susceptible strains of Aeromonas salmonicida. strains of Aeromonas salmonicida. USP, 2000f USP, 2000f

Sarafloxacin Sarafloxacin Indicated in the treatment of furunculosis, vibriosis and enteric Indicated in the treatment of furunculosis, vibriosis and enteric redmouth in Salmonidae. redmouth in Salmonidae. EMEA, 1997 EMEA, 1997

Erythromycin Erythromycin In the treatment of bacterial kidney disease (Renibacterium In the treatment of bacterial kidney disease (Renibacterium salmoninarum) and streptococcosis in yellowtail in Japan. salmoninarum) and streptococcosis in yellowtail in Japan. GESAMP, 1997 GESAMP, 1997

Sulphonamides Sulphonamides potentiated with potentiated with trimethoprim or trimethoprim or ormethoprim ormethoprim

Against furunculosis, enteric redmouth disease and vibriosis. Against furunculosis, enteric redmouth disease and vibriosis. GESAMP, 1997 GESAMP, 1997

HACCP vis-à-vis prevention / control HACCP vis-à-vis prevention / control strategies for the prevention of strategies for the prevention of

antibiotics in fish and fisheries products.antibiotics in fish and fisheries products.

Unregulated/unapproved drugs administered to Unregulated/unapproved drugs administered to aquacultured fish pose a potential human health aquacultured fish pose a potential human health hazard.hazard.

These substances may be carcinogenic, allergenic, These substances may be carcinogenic, allergenic, and/or may cause antibiotic resistance in manand/or may cause antibiotic resistance in man

As the fact goes, the processors should clearly As the fact goes, the processors should clearly understand that antibiotics once got into their understand that antibiotics once got into their product, cannot be removed by any known methods. product, cannot be removed by any known methods.

So only option they have is to receive raw material So only option they have is to receive raw material which do not have any residue of antibiotics. which do not have any residue of antibiotics.

On-farm visits to review drug usage before receipt of the product, On-farm visits to review drug usage before receipt of the product, coupled with a supplier's lot-by-lot certificate that any antibiotic coupled with a supplier's lot-by-lot certificate that any antibiotic administered were used in conformance with the application administered were used in conformance with the application requirements;requirements;

Receipt of supplier's lot-by-lot certification of proper drug usage, Receipt of supplier's lot-by-lot certification of proper drug usage, coupled with appropriate verification coupled with appropriate verification

Review of drug usage records kept at the farm by auditing the farm Review of drug usage records kept at the farm by auditing the farm periodically and at receipt of the product, coupled with a supplier's lot-periodically and at receipt of the product, coupled with a supplier's lot-by-lot certificate that any drug used were used in conformance with the by-lot certificate that any drug used were used in conformance with the application requirements;application requirements;

Drug residue testing;Drug residue testing;

Receipt of evidence (e.g. third party certificate) that the producer Receipt of evidence (e.g. third party certificate) that the producer operates under a third party- audited Quality Assurance Program for operates under a third party- audited Quality Assurance Program for aquaculture drug use.aquaculture drug use.

Observation of required withdrawal period.Observation of required withdrawal period.

Thank you for your attentionThank you for your attention

ANTIBIOTICS CHEMICAL HAZARDS BY ASHOK SIR

Technology

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