This document discusses chemical hazards in antibiotics, specifically: 1. It categorizes chemical hazards into naturally occurring, intentionally added, and unintentionally added chemicals. Antibiotics can contain unintentionally added chemicals from raw materials or packaging. 2. It describes various mechanisms of action of antibacterial drugs including inhibition of cell wall synthesis, protein synthesis, nucleic acid synthesis, and metabolic pathways. 3. It discusses EU legislation around antibiotic residues in food including definitions of maximum residue limits and prohibited substances. Monitoring programs help enforce regulations and issue alerts when risks are detected.

1. Antibiotics – Chemical Hazard Ashok Kumar K

5. 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.

6. 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)

8. Ehrlich’s Magic Bullets

9. Fleming and Penicillin

30. 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 nutrients for 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

31. 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

32. EU legislation on residues

35. The Limits

40. Official Control

58. Rapid Alert System

64. 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 INFORMATION ALERT TRANSMISSION OF NOTIFICATIONS TO THE THIRD COUNTRIES CONCERNED MEMBER STATES COMMISSION SERVICES E-MAIL FAX REPORTS/ STATISTICS

68. 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.

69. Antibiotics banned for animals intended for food production. Antibiotic Country Reason Reference Spectinomycin USA Its use is limited by the ready development of bacterial resistance USP, 2000d. Enrofloxacin USA Its use is limited by the ready development of bacterial resistance (quinolone) USP, 2000h. Cloramphenicol Argentina, Canada, EU, Japan, USA, India Induces human aplastic anaemia USP, 2000e; GESAMP, 1997; SANCO, 2001a. Nitrofurans Argentina, Canada, EU, Japan, USA,India Carcinogenicity and mutagenicty USP, 2000e; GESAMP, 1997; SANCO, 2001a Rifampin Not labelled in USA or Canada for use in animals, including food-producing animals Tumorgenicity and teratogenic effects on experimental animals USP, 2000k.