benzodiazepines in animal-derived foods?

I've not checked to see if this 2015 study abstract has already been posted here, but it seems to imply that food animals are being fed benzos.    (As though daily administration of low-dose antibiotics via feed isn't concerning enough.)

 

https://pubmed.ncbi.nlm.nih.gov/25421624/

 

Production of Monoclonal Antibody Against Clonazepam for Immunoassay of Benzodiazepine Drugs in Swine Tissues

Wen C Shan 1, Ya L Cui, Xin He, Lei Zhang, Jing Liu, Jian P Wang

Affiliations expand

PMID: 25421624 DOI: 10.1080/03601234.2015.964620

 

Abstract

 

The objective of the present study was to produce a generic monoclonal antibody for immunoassay of residues of benzodiazepine drugs in swine tissues. Clonazepam was used to synthesize a hapten that was coupled to bovine serum albumin as an immunogen for the production of monoclonal antibody. Results showed that the obtained monoclonal antibody was able to recognize five benzodiazepine drugs simultaneously (clonazepam, flunitrazepam nitrazepam, diazepam, and oxazepam). The cross-reactivities were in the range of 24-100% and the limits of detection were in the range of 0.2-1.5 ng mL(-1) depending on the drug. Then a competitive indirect enzyme-linked immunosorbent assay was developed to determine the residues of five benzodiazepines in swine tissues (muscle, liver and kidney). The recoveries of five analytes from the fortified blank samples were in the range of 74.5-96.5% with coefficients of variation lower than 16.7%. Therefore, this immunoassay could be used as a rapid and simple method for the screening of residues of five benzodiazepine drugs in animal-derived foods.

I've not checked to see if this 2015 study abstract has already been posted here, but it seems to imply that food animals are being fed benzos.    (As though daily administration of low-dose antibiotics via feed isn't concerning enough.)

 

https://pubmed.ncbi.nlm.nih.gov/25421624/

 

Production of Monoclonal Antibody Against Clonazepam for Immunoassay of Benzodiazepine Drugs in Swine Tissues

Wen C Shan 1, Ya L Cui, Xin He, Lei Zhang, Jing Liu, Jian P Wang

Affiliations expand

PMID: 25421624 DOI: 10.1080/03601234.2015.964620

 

Abstract

 

The objective of the present study was to produce a generic monoclonal antibody for immunoassay of residues of benzodiazepine drugs in swine tissues. Clonazepam was used to synthesize a hapten that was coupled to bovine serum albumin as an immunogen for the production of monoclonal antibody. Results showed that the obtained monoclonal antibody was able to recognize five benzodiazepine drugs simultaneously (clonazepam, flunitrazepam nitrazepam, diazepam, and oxazepam). The cross-reactivities were in the range of 24-100% and the limits of detection were in the range of 0.2-1.5 ng mL(-1) depending on the drug. Then a competitive indirect enzyme-linked immunosorbent assay was developed to determine the residues of five benzodiazepines in swine tissues (muscle, liver and kidney). The recoveries of five analytes from the fortified blank samples were in the range of 74.5-96.5% with coefficients of variation lower than 16.7%. Therefore, this immunoassay could be used as a rapid and simple method for the screening of residues of five benzodiazepine drugs in animal-derived foods.

 

Please share validated reports where benzodiazepines are used in the meat production industry. I have been associated with beef & pork production all of my life and I have never seen or heard of the use of benzodiazepines for those meat production industries. 

I've not checked to see if this 2015 study abstract has already been posted here, but it seems to imply that food animals are being fed benzos.    (As though daily administration of low-dose antibiotics via feed isn't concerning enough.)

 

https://pubmed.ncbi.nlm.nih.gov/25421624/

 

Production of Monoclonal Antibody Against Clonazepam for Immunoassay of Benzodiazepine Drugs in Swine Tissues

Wen C Shan 1, Ya L Cui, Xin He, Lei Zhang, Jing Liu, Jian P Wang

Affiliations expand

PMID: 25421624 DOI: 10.1080/03601234.2015.964620

 

Abstract

 

The objective of the present study was to produce a generic monoclonal antibody for immunoassay of residues of benzodiazepine drugs in swine tissues. Clonazepam was used to synthesize a hapten that was coupled to bovine serum albumin as an immunogen for the production of monoclonal antibody. Results showed that the obtained monoclonal antibody was able to recognize five benzodiazepine drugs simultaneously (clonazepam, flunitrazepam nitrazepam, diazepam, and oxazepam). The cross-reactivities were in the range of 24-100% and the limits of detection were in the range of 0.2-1.5 ng mL(-1) depending on the drug. Then a competitive indirect enzyme-linked immunosorbent assay was developed to determine the residues of five benzodiazepines in swine tissues (muscle, liver and kidney). The recoveries of five analytes from the fortified blank samples were in the range of 74.5-96.5% with coefficients of variation lower than 16.7%. Therefore, this immunoassay could be used as a rapid and simple method for the screening of residues of five benzodiazepine drugs in animal-derived foods.

 

https://www.fsis.usda.gov/wps/wcm/connect/22dd2ec9-2e85-46f8-8d81-32456616fbbf/QandA2018.pdf?MOD=AJPERES

 

"The Food Safety and Inspection Service"

 

 

 

You misunderstand the goal of this study. It was done to produce antibodies against benzos so that using these antibodies benzos then can then be tested in human samples. This similar to when animals are immunized with diphteria toxin (or even coronavirus), so that antibodies can be harvested for treating or testing diseases. In addition, they don't feed the animals, they inject them because feeding will not induce an antibody response.

Please share validated reports where benzodiazepines are used in the meat production industry. I have been associated with beef & pork production all of my life and I have never seen or heard of the use of benzodiazepines for those meat production industries.

 

My bad.  BDZs are injected into (not fed to) food animals, primarily for sedation and anesthesia purposes, and in some European countries, as an appetite stimulant.  With that said, residue and withdrawal interval studies are lacking.  Thus, the need for development of residue screening methods, such as the immunoassay for benzodiazepines in swine tissue that began this thread.     

 

Food Animal Residue Avoidance Databank (FARAD)

Extralabel use of tranquilizers and general anesthetics

"Tiletamine Hydrochloride end Zolazepam

Telazol is a combination product of tiletamine hydrochloride (an anesthetic in the ketamineiphencyclidine hydrochloride class) and zolazepam (benzodiazepine tranquilizer). The FARAD has received numerous requests for WDI [withdrawal interval] recommendations for use of Telazol in food animals. An extensive literature search failed to find any relevant published articles on which a recommendation could be based, and a search of veterinary drug compendia from 5 foreign countries failed to discover any foreign food animal approval. At this time, FARAD cannot provide a WDI recommendation for Telazol."

http://www.farad.org/publications/digests/081997ExtralabelTranquilizers.pdf

 

 

Farm Animal Anesthesia: Cattle, Small Ruminants, Camelids, and Pigs

HuiChu Lin, Paul Walz

John Wiley & Sons, Apr 8, 2014

From pages 233,234

"The minor tranquilizers, diazepam and midazolam, are used for their anxiolytic, anticonvulsant, and central muscle-relaxing effects.  They are suitable for use alone, or for induction of anesthesia when combined with an anesthetic such as ketamine....  Additionally, benzodiazepines have a short-lived appetite-stimulating effect.  An injectable formulation containing brotizolam (Mederantil) is commercially available and approved for use as appetite stimulation in cattle in some European countries.

"Elimination kinetics and other pharmacokinetic characteristics vary greatly between species, making the extrapolation of appropriate withdrawal times from other species difficult.  The prevention of benzodiazepine residues in tissues of farm animals is critical because adverse effects can occur in humans.  Pharmacokinetic and residue studies guiding withdrawal time recommendations for benzodiazepines in food-producing animals are currently lacking.  Therefore, a conservative estimate of withdrawal time of 30 days for meat should be used.  For IV doses of diazepam of up to 0.1 mg/kg in cattle and small ruminants, FARAD recommends a withdrawal time of 10 days (FARAD email communication, Dec 2013).  Benzodiazepines should not be used in lactating dairy cattle."

https://books.google.com/books?id=eo5UAwAAQBAJ&pg=PA233&lpg=PA233&dq=benzodiazepine+residues+in+food+animals&source=bl&ots=ZcHwGycLZO&sig=ACfU3U3xOWJ8cicsBfOgwcvCCdEFxnf7AQ&hl=en&sa=X&ved=2ahUKEwi_07Ga2_zpAhW1RTABHeaBC_UQ6AEwCHoECAcQAQ#v=onepage&q=benzodiazepine%20residues%20in%20food%20animals&f=false

 

You misunderstand the goal of this study. It was done to produce antibodies against benzos so that using these antibodies benzos then can then be tested in human samples.

 

Sure, this immunoassay methodology could probably be used for post-mortem analysis of benzodiazepine residues in human muscle, liver and kidney tissue samples, as well as in food animal tissues.  Not sure it's an either/or thing. 

(As though daily administration of low-dose antibiotics via feed isn't concerning enough.)

 

 

https://www.fsis.usda.gov/wps/wcm/connect/22dd2ec9-2e85-46f8-8d81-32456616fbbf/QandA2018.pdf?MOD=AJPERES

 

"The Food Safety and Inspection Service"

 

Global trends in antimicrobial resistance in animals in low- and middle-income countries

Science  20 Sep 2019:  Vol. 365, Issue 6459

Thomas P. Van Boeckel, João Pires, Reshma Silvester, Cheng Zhao, Julia Song, Nicola G. Criscuolo, Marius Gilbert, Sebastian Bonhoeffer, Ramanan Laxminarayan

Abstract

"The global scale-up in demand for animal protein is the most notable dietary trend of our time. Antimicrobial consumption in animals is threefold that of humans and has enabled large-scale animal protein production. The consequences for the development of antimicrobial resistance in animals have received comparatively less attention than in humans. We analyzed 901 point prevalence surveys of pathogens in developing countries to map resistance in animals. China and India represented the largest hotspots of resistance, with new hotspots emerging in Brazil and Kenya. From 2000 to 2018, the proportion of antimicrobials showing resistance above 50% increased from 0.15 to 0.41 in chickens and from 0.13 to 0.34 in pigs. Escalating resistance in animals is anticipated to have important consequences for animal health and, eventually, for human health."

https://science.sciencemag.org/content/365/6459/eaaw1944

 

 

Please share validated reports where benzodiazepines are used in the meat production industry. I have been associated with beef & pork production all of my life and I have never seen or heard of the use of benzodiazepines for those meat production industries.

 

My bad.  BDZs are injected into (not fed to) food animals, primarily for sedation and anesthesia purposes, and in some European countries, as an appetite stimulant.  With that said, residue and withdrawal interval studies are lacking.  Thus, the need for development of residue screening methods, such as the immunoassay for benzodiazepines in swine tissue that began this thread.     

 

Food Animal Residue Avoidance Databank (FARAD)

Extralabel use of tranquilizers and general anesthetics

"Tiletamine Hydrochloride end Zolazepam

Telazol is a combination product of tiletamine hydrochloride (an anesthetic in the ketamineiphencyclidine hydrochloride class) and zolazepam (benzodiazepine tranquilizer). The FARAD has received numerous requests for WDI [withdrawal interval] recommendations for use of Telazol in food animals. An extensive literature search failed to find any relevant published articles on which a recommendation could be based, and a search of veterinary drug compendia from 5 foreign countries failed to discover any foreign food animal approval. At this time, FARAD cannot provide a WDI recommendation for Telazol."

http://www.farad.org/publications/digests/081997ExtralabelTranquilizers.pdf

 

 

Farm Animal Anesthesia: Cattle, Small Ruminants, Camelids, and Pigs

HuiChu Lin, Paul Walz

John Wiley & Sons, Apr 8, 2014

From pages 233,234

"The minor tranquilizers, diazepam and midazolam, are used for their anxiolytic, anticonvulsant, and central muscle-relaxing effects.  They are suitable for use alone, or for induction of anesthesia when combined with an anesthetic such as ketamine....  Additionally, benzodiazepines have a short-lived appetite-stimulating effect.  An injectable formulation containing brotizolam (Mederantil) is commercially available and approved for use as appetite stimulation in cattle in some European countries.

"Elimination kinetics and other pharmacokinetic characteristics vary greatly between species, making the extrapolation of appropriate withdrawal times from other species difficult.  The prevention of benzodiazepine residues in tissues of farm animals is critical because adverse effects can occur in humans.  Pharmacokinetic and residue studies guiding withdrawal time recommendations for benzodiazepines in food-producing animals are currently lacking.  Therefore, a conservative estimate of withdrawal time of 30 days for meat should be used.  For IV doses of diazepam of up to 0.1 mg/kg in cattle and small ruminants, FARAD recommends a withdrawal time of 10 days (FARAD email communication, Dec 2013).  Benzodiazepines should not be used in lactating dairy cattle."

https://books.google.com/books?id=eo5UAwAAQBAJ&pg=PA233&lpg=PA233&dq=benzodiazepine+residues+in+food+animals&source=bl&ots=ZcHwGycLZO&sig=ACfU3U3xOWJ8cicsBfOgwcvCCdEFxnf7AQ&hl=en&sa=X&ved=2ahUKEwi_07Ga2_zpAhW1RTABHeaBC_UQ6AEwCHoECAcQAQ#v=onepage&q=benzodiazepine%20residues%20in%20food%20animals&f=false

 

https://nifa.usda.gov/food-animal-residue-avoidance-databank

Food Animal Residue Avoidance Databank

 

"Livestock producers, veterinarians, and feed producers recognize food residue avoidance as the key to consumer confidence, and they are enhancing and formalizing programs that will permeate every facet of the production system. The development of effective residue avoidance and quality assurance programs requires access to a vast array of information. The Food Animal Residue Avoidance Databank (FARAD) offers the means to provide this information.

 

NIFA administers the funding that establishes and maintains FARAD, a computer-based decision support system designed to provide livestock producers, extension specialists, and veterinarians with practical information on how to avoid drug, pesticide, and environmental contaminant residue problems. The drugs and pesticides used in modern animal agriculture improve animal health and thereby promote more efficient and humane production.

 

Wherever drugs are used to treat sick animals or prevent disease, there is a potential that residues may be incurred. The U.S. Food and Drug Administration (FDA), which must approve all drugs meant to be marketed for use in animals, establishes tolerances for drug residues (similar to speed limits) to ensure food safety. The FDA also establishes “withdrawal times” or “withholding periods,” which are times after drug treatment when milk and eggs are not to be used for food and during which animals are not to be slaughtered. This allows time for the animals to eliminate the drug residues.

 

FARAD is a repository of comprehensive residue avoidance information. FARAD also is sanctioned to provide these estimates to the U.S. Pharmacopeia-Drug Information (USP-DI) Veterinary Medicine Advisory Committee. Since 1982, FARAD has been working with producers, extension specialists and agents, and veterinarians to help avoid and mitigate residue problems. As a cooperative multistate program, FARAD is available nationwide to offer advice about residue avoidance."

 

I really don't understand the purpose of the original post. The performance of countries based on their 2019 food security score indicates the U.S. is ranked 3rd overall & 4th in quality and safety among the 113 listed countries in the Global Food Security Index:

 

https://foodsecurityindex.eiu.com/Index

 

My suggestion for very concerned consumers is to grow your own & avoid bats. Best Wishes

My suggestion for very concerned consumers is to grow your own

Actually, we do grow a fair amount of it.  We enjoy fresh eggs and goat milk daily and just used the last of our pasture-raised, home-butchered, heritage-breed pork.  So I'm not anti-carnivore or anti-meat, nor am I "out to get" farmers, without whom the vast majority of Americans would starve.    

 

I really don't understand the purpose of the original post. The performance of countries based on their 2019 food security score indicates the U.S. is ranked 3rd overall & 4th in quality and safety among the 113 listed countries in the Global Food Security Index

I had never heard of BZDs being used in the livestock industry, and you said you hadn't either.  So it's not out-of-line to have posted the article on this subforum, nor to have questioned how and why benzos are getting into enough food animals in sufficient quantities that a method had to be developed to analyze for the stuff in livestock tissue. I admit, however, that my speculation that it was orally administered was uninformed, and for that I apologize.

 

Wherever drugs are used to treat sick animals or prevent disease, there is a potential that residues may be incurred. The U.S. Food and Drug Administration (FDA), which must approve all drugs meant to be marketed for use in animals, establishes tolerances for drug residues (similar to speed limits) to ensure food safety. The FDA also establishes “withdrawal times” or “withholding periods,” which are times after drug treatment when milk and eggs are not to be used for food and during which animals are not to be slaughtered. This allows time for the animals to eliminate the drug residues.

Yes, the purpose of withdrawal times, and the need for more studies, was discussed at length in previous excerpts.

 

While I'd love to have every confidence in the FDA, I don't.  The agency's regulation of BZDs in human patients is only beginning to come up to speed--60 years after the first BZD was approved.   

 

At any rate, it's now clear that the immunoassay method will be (has been?) used to conduct studies to determine BZD withdrawal intervals for large food animal species, which, as we learned today, can have very different BZD elimination profiles. Establishing these withdrawal intervals will make it possible to safely eat meat from animals that have undergone BZD sedation/anesthesia.

 

Thanks for the constructive discussion--exactly what the "Chewing the fat" subforum is designed for, right?