Observations of the Effects of Chloramphenicol and Starvation on the Hemopoietic System of the Dog

Penny, Ralph; Watson, A. D. J.; Moyle, G. G.

doi:10.3109/15563657308990522

Cited by 13 publications

(6 citation statements)

References 9 publications

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“…It was noted that a coinciding reduction in appetite, and consequently malnutrition, might have been a contributing/complicating factor. This latter finding is further supported in experiments by Penny et al (1973), in which 50 mg/kg b.w. per day produced no bone marrow changes; in contrast, a dose of 150 mg/kg b.w.…”

Section: Companion Animalssupporting

confidence: 77%

Scientific Opinion on Chloramphenicol in food and feed

2014

EFS2

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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...

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Section: Companion Animalssupporting

confidence: 77%

Scientific Opinion on Chloramphenicol in food and feed

2014

EFS2

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“…The finding of individual cell necrosis represents the first observation of cytotoxicity associated with exposure to FFC in fish. Although individual cell necrosis was observed in the anterior kidney, the cytotoxic changes observed were exceedingly minor relative to the clinical manifestations of amphenicol (chloramphenicol, thiamphenicol, and FFC)-induced impairment of the myeloid function (e.g., decreased number of circulating white blood cells [especially neutrophils], cytologic/histopathologic change [vacuolation, degeneration, necrosis, maturation arrest, and reduced cellularity]; Ferrari and Pajola 1981;Keiser and Buchegger 1973;Penny, Watson, and Moyle 1973;Watson 1977) in laboratory rats and dogs at high doses (200-300 mg/kg BW).…”

Section: Discussionmentioning

confidence: 99%

Safety of Florfenicol Administered in Feed to Tilapia (Oreochromis sp.)

et al. 2012

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The safety of Aquaflor 1 (50% w/w florfenicol [FFC]) incorporated in feed then administered to tilapia for 20 days (2Â the recommended duration) at 0, 15, 45, or 75 mg/kg body weight/day (0, 1, 3, or 5Â the recommended dose of 15 mg FFC/kg BW/d) was investigated. Mortality, behavioral change, feed consumption, body size, and gross and microscopic lesions were determined. Estimated delivered doses were >96.9% of target. Three unscheduled mortalities occurred but were considered incidental since FFC-related findings were not identified. Feed consumption was only affected during the last 10 dosing days when the 45 and 75 mg/kg groups consumed only 62.5% and 55.3% of the feed offered, respectively. There were significant, dose-dependent reductions in body size in the FFC-dose groups relative to the controls. Treatment-related histopathological findings included increased severity of lamellar epithelial hyperplasia, increased incidence of lamellar adhesions, decreased incidence of lamellar telangiectasis in the gills, increased glycogen-type and lipid-type hepatocellular vacuolation in the liver, decreased lymphocytes, increased blast cells, and increased individual cell necrosis in the anterior kidney, and tubular epithelial degeneration and mineralization in the posterior kidney. These changes are likely to be of minimal clinical relevance, given the lack of mortality or morbidity observed. This study has shown that FFC, when administered in feed to tilapia at the recommended dose (15 mg FFC/kg BW/day) for 10 days would be well tolerated.

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“…In contrast, toxic changes in the hematopoietic tissues were induced in laboratory rats and dogs at very high doses (200-300 mg/kg body weight) of amphenicol antibiotics (chloramphenicol, thiamphenicol, and florfenicol). The clinical manifestations of amphenicol-induced impairment of the myeloid function included decreased number of circulating white blood cells (especially neutrophils) and cytologic/histopathologic evidence of vacuolation, degeneration, necrosis, maturation arrest, and reduced cellularity (9,18,24,36).…”

Section: Discussionmentioning

confidence: 99%

Safety of Aquaflor (Florfenicol, 50% Type A Medicated Article), Administered in Feed to Channel Catfish, Ictalurus punctatus

Gaikowski

Wolf

Endris³

et al. 2003

Toxicol Pathol

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Aquaflor, a feed premix containing the broad spectrum antibacterial agent florfenicol (50% w/w), is being developed for use to control enteric septicemia (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative enterobacterium Edwardsiella ictaluri. The recommended dose of Aquaflor to control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was to determine the safety of Aquaflor administered in feed to channel catfish at doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days. Parameters evaluated included daily mortality, behavioral (appetite, distribution, flight/fright response), and water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Medicated feed consumption was 67-86% of target with group mean doses of 8.5 mg/kg BW/day, 24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically observable changes noted at any of the dose levels tested. Aquaflor-related changes were limited to the food consumption and histopathology data. Although Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg BW/day groups, there were no differences in fish growth among the treatment groups. Aquaflor-related histopathology findings were limited to a histomorphologically evident dose-dependent decrease in hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys, and spleens of channel catfish.

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Observations of the Effects of Chloramphenicol and Starvation on the Hemopoietic System of the Dog

Cited by 13 publications

References 9 publications

Scientific Opinion on Chloramphenicol in food and feed

Scientific Opinion on Chloramphenicol in food and feed

Safety of Florfenicol Administered in Feed to Tilapia (Oreochromis sp.)

Safety of Aquaflor (Florfenicol, 50% Type A Medicated Article), Administered in Feed to Channel Catfish, Ictalurus punctatus

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