Scientific Opinion on Chloramphenicol in food and feed

Abstract

Chloramphenicol is an antibiotic not authorised for use in food-producing animals in the European Union (EU). However, being produced by soil bacteria, it may occur in plants. The European Commission asked EFSA for a scientific opinion on the risks to human and animal health related to the presence of chloramphenicol in food and feed and whether a reference point for action (RPA) of 0.3 µg/kg is adequate to protect public and animal health. Data on occurrence of chloramphenicol in food extracted from the national residue monitoring plan results and from the Rapid Alert System for Food and Feed (RASFF) were too limited to carry out a reliable human dietary exposure assessment. Instead, human dietary exposure was calculated for a scenario in which chloramphenicol is present at 0.3 µg/kg in all foods of animal origin, foods containing enzyme preparations and foods which may be contaminated naturally. The mean chronic dietary exposure for this worst-case scenario would range from 11 to 17 and 2.2 to 4.0 ng/kg b.w. per day for toddlers and adults, respectively. The potential dietary exposure of livestock to chloramphenicol was estimated to be below 1 µg/kg b.w. per day. Chloramphenicol is implicated in the generation of aplastic anaemia in humans and causes reproductive/hepatotoxic effects in animals. Margins of exposure for these effects were calculated at 2.4 × 10 5 or greater and the CONTAM Panel concluded that it is unlikely that exposure to food contaminated with chloramphenicol at or below 0.3 µg/kg is a health concern for aplastic anaemia or reproductive/hepatotoxic effects. Chloramphenicol exhibits genotoxicity but, owing to the lack of data, the risk of carcinogenicity cannot be assessed. The SUMMARYChloramphenicol is a broad-spectrum antibiotic effective against Gram-positive and Gram-negative bacteria and, in the past, has been widely used to treat infections in both humans and animals. Chloramphenicol is not authorised for use in food-producing animals in the European Union (EU) but may be used in human medicine and in treatments for non-food-producing animals. Apart from its potential occurrence as a residue in food from illicit treatment of food-producing animals, chloramphenicol has also been used in feed and food enzyme products and may occur naturally in plants from its production by the soil bacterium Streptomyces venezuelae.The EFSA Scientific Opinion entitled "Guidance on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin" identified an approach for establishing RPAs for various categories of non-allowed pharmacologically active substances. However, the opinion also identified certain categories of non-allowed pharmacologically active substances that are considered to be outside the scope of the procedure, including substances causing blood dyscrasias (aplastic anaemia) such as chloramphenicol. As chloramphenicol is excluded fro...

Metabolomic Profile of Primary Turkey and Rat Hepatocytes and Two Cell Lines after Chloramphenicol Exposure

“…This is very interesting because CAP metabolism in primary turkey hepatocyte cultures has never been studied. The in vivo studies with poultry indicate that CAP metabolism differs from that of rats in the formation and excretion of glucuronide and reduction of the nitro group [2,42]. We found that the concentrations of the nontoxic metabolite, CAP-G, in turkey hepatocyte cultures were lower than those in equivalent rat hepatocyte cultures.…”

“…Chloramphenicol (CAP) is a broad-spectrum antibiotic used in medicine. Its use in food-producing animals is banned due to the potentially carcinogenic action of CAP residue and the development of non-dose-related aplastic anemia in humans [1,2]. However, this antibiotic is used illegally in veterinary practice, and its residues are found in food from animals (milk (0.005-0.5 µg/L), honey (0.1-75 µg/kg), eggs (0.9 µg/kg), fish and shrimp (0.01-242 µg/kg), meat (0.004-0.01 µg/kg), turkey breasts (1-8.7 µg/kg), and chicken breasts (range, 0.4-1.2 µg/kg)) [3][4][5] and the environment (sediments (0.196 mg/kg), surface water (112 ng/kg)) [6][7][8][9].…”

“…CAP is rapidly absorbed following oral administration and distributed throughout the organs and tissues in animals and humans. The use of CAP in humans can lead to serious hematologic and metabolic toxicity (e.g., "gray baby syndrome" in newborns and young infants) [1,2]. The drug is metabolized primarily in the liver [10] and its use by patients with liver cancer may pose a risk of adverse drug reaction [11].…”

“…The drug is metabolized primarily in the liver [10] and its use by patients with liver cancer may pose a risk of adverse drug reaction [11]. Additionally, the drug shows toxicity to the liver and reproductive system in animals [2]. The mechanism of CAP's toxicity is complex and differs from species to species, depending mainly on how CAP undergoes biotransformation [1,12].…”

“…The mechanism of CAP's toxicity is complex and differs from species to species, depending mainly on how CAP undergoes biotransformation [1,12]. According to the European Food Safety Authority (EFSA), research on CAP should focus on the potential formation of reactive (toxic) metabolites of the antibiotic in different animal species, which may result in the presence of residues in food of animal origin [2]. To our knowledge there is no information about metabolites of CAP in turkeys.…”