General Background about Sulfonamide

From 1950s the antimicrobial agent has been widely applied on animals, because it has contributed significantly to the growth promotion, and treatment and or prevention of infectious disease. (Haoet al., 2016)

It is given nowadays for growth promotion also in very low doses like an additive for the animal which it enhances absorption of nutrient in the intestine, suppresses the gut bacteria and it also destroys pathogens that reduce the release of toxins therefore improving animal's physiological performance and its growth rate which increases the profit and the production of food (Prajwal et al.

,2017)

There are many factors that result in veterinary medical drug residue in animal food during slaughtering, some include age, and feeding practices of the animals, other include the drug absorption, biotransformation and excretion, however failure of keeping withdrawal period and overdose and extra label are the most common and threatening. (Beyene, T.,2015)

Sulfonamide is one of the veterinary medical drug, it is a popular agent since it has a great antibacterial property against diseases, also it is cheap and has minimal toxicity (Unsal et al.

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,2018)

Sulfonamide is used to treat infection that result from protozoa, fungi and parasites in addition to a wide range of gram positive and gram negative bacteria, for example sulfathiazole is used against panibacillus larvae in order to decrease its infection, minimize its spread and prevent spore germination (Bitas et al., 2018)

Sulfonamide is used to treat and to prevent coccidiosis which is a parasitic disease caused by Eimeria species, it manifests itself on the epithelial tissue of the intestine and causes morbidity and mortality in birds.

(Mond et al.,2016)

The mode of action of this drug is based on its competition with para-aminobenzoic acid which is responsible for the synthesis of folic acid, therefore it deteriorates the development of bacterial cells (Lahcen & Amine.,2018)

Although several SAs are used simultaneously in human and veterinary medicine, some SAs present specificity for veterinary use, such as sulfaquinoxaline (Hoff et al.,2016)

Sulfonamide is still being widely used despite of its declining due to jurisdictions, to be specific sulfamethazine is used to treat diarrhea in calves, also to treat septicemia and pneumonia in swine, and to treat Escherichia coli and pasturella multocide in turkey. (Baynes et al., 2016)

It is known that there are more than 10,000 sulfonamide derivatives that have been synthesized but there are only 40 derivatives are used in veterinary and human medicines, as for Sulfamethoxazole, sulfacetamide, and sulfasalazine are the mostly sulfonamide derivatives used in human medicine while sulfadimethoxine, sulfathiazole, sulfamerazine, sulfadiazine, and sulfamethazine are the most commonly applied for veterinary usage. (Lahcen, A., & Amine, 2017).

Sulfonamide is easily absorbed and accumulated in several tissues in poultry if its administration exceed limits (Muhtabeddine et al .,2012) its residue vary from tissue to another where high concentrations are seen in liver and kidney since they are storage tissues (Muhtabeddine et al .,2012)

Sulfonamide is one of the antibiotics having MRL that its use is being regularly monitored specifically because it has a high rate of violation in USA and a strong debate for its public health concern (Marni S et al.,2017)

MRL is the maximum residual concentration that is legally accepted in animal feed, food diet and agricultural commodity (K. Jayalakshmi et al.,2017)

For the EU,food safety is a legal framework and an important issue maximize the level of consumers protections and to prevent him from various hazards and contaminants (Murat Metli et al .,2015)

According to EU, MRLset for sulfonamide in edible tissue is 100 µg/kg (Govind V et al .,2018

As for milk EU and codex alimentarious regulations state MRL of 100 µg/kg also. (Joy Deborah Orwa et al .,2017)

Many analytical methods for food analysis have been used to detect sulfonamide residues in animal products among them are LC liquid chromatography coupled with MS (mass spectrophotometry or UV ultraviolet of FL fluorescence; these are able to detect 300 compound or more in animal feed. (Manual Gonzalez Ronquillo and Juan Carlor Angeles Hernadez ,2017)

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the most proper technique to analyze residues since it is sensitive, selective and able to detect polar compound and or volatile compounds (Unsal et al.,2018 )

LC-MS can identify antibiotics and or its metabolites only if previously selected as targets, but screening methods like microbiological assays can identify any antibiotics or its metabolite. (Merve Bacanli and Nursen Basaran.,2019)

Even though many analytical methods are widely used for detection of many residues, HPLC is the best and most commonly used (Neelma Ashraf .,2018)

Health effects for sulfonamide on human body

All antimicrobials when taken therapeutically by patients can cause allergic reactions, for example sulfonamide that causes skin rashes, asthma and in severe cases anaphylactic shock (Abdul Sajid et al .,2016) Therefore it is important to know the adverse effect of sulfonamide detected in food product as well as taken orally for therapeutic reasons .

Many antimicrobial agents have been used clinically humans and in food animals that's why there is a potential of spreading the antibiotic resistant bacteria from animals directly through food to humans, this hazard causes decreasing the effect of treating resistant infectious disease in patients which is an important health consequence to be aware of. (Hao et al.,2016)

When people consume milk and other animal product with high level of antimicrobial residues many health concern like liver poisoning and permanent mutation of a gene can occur (Joy Dobrah Orwa et al .,2017)

Sulfonamide residue causes many health effects on consumers. It affects the urinary system and the hemopoietic system. In addition, it causes allergic reaction, alteration of intestinal flora and drug resistance, the 3 pathogenicity effect (teratogenetic, carcinogenic and mutagenic) are also health hazards of sulfonamide on the human body. (Jiang J and Wang G ,2017)

Generally low level of drug residue does not cause public health problem but extensive use may harm the consumer (Beyene, T.,2015)

According to Nisha (2008) Sulphamethazine causes transfer of antibiotic resistant strains from bacteria to consumers also it causes autoimmunity disorders, immunologic effects and carcinogenicity (Vishnuraj et al.,2016).

SDM (sulfadimethoxine) and SMZ sulfamethazine antimicrobials when used improperly in lactating cows can precipitate in the milk that is consumed by a growing child every day therefore SMZ is a potential carcinogen, its withdrawal time is estimated to be 15 days (Kebede et al ., )in addition persistent sulfamethazine residues in the body is known to cause carcinogenicity and autoimmune pathology (Muhamad dannish Mond et al .,2016)

For this reason, FDA has banned the extra label usage of sulfonamide in lactating animals (Merve Bacanli and Nursen Basaran .,2019)

Because of the long term use of sulfonamides, a large number of sulfonamide bacterial strains has emerged, which caused the stimulation of production of combined sulfonamide preparation consisting of trimethoprim like Bactrim and Septrin. in order to delay the proliferation of these resistant microorganism and also to enhance the effect of sulfonamide (Dmitrienko et al.,2014)

The main goal nowadays is to reduce antibiotic resistance and allergic reactions, in order to achieve food safety hence antibiotics and growth promoter's drugs should be reduced and monitored (Manual Gonzalez Ronquillo and Juan Carlor Angeles Hernadez ,2017)

The controlled antimicrobial administration and the efficient surveillance of antimicrobial resistant among population has really decreased the prevalence of antimicrobial resistant in developed countries like United Kingdom and Sweden (Melanie Gondam Kamini et al.,2016)

Several articles about detecting sulfonamide in many animal products are discussed below

In a study conducted in turkey its aim is to estimate 7 group of antimicrobial residue and to compare them with turkey and EU tolerance limit. The samples were 10 pieces of 0.5 kg of chicken liver from 34 poultries. The results show that only one sample contain antimicrobial residues which are higher than the limits, as Trimethoprim (298.5 µg/kg) and Sulfametoxazole (312.8 µg/kg) To conclude European union and turkey banned the use of antibiotics as growth promoter for a long period of time (Metli et al.,2019)

Another study was conducted in France, its aim is to assess the veterinary drug and its compliance to MRL levels also to identify the reasons behind the presence of prohibited substance and the presence of high veterinary drug residues like sulfonamide which causes toxicological affect to the consumers. Tandem mass spectrometry is used for the detection for prohibited substance ,however a varied methods are used for different antibiotics which include liquid and planar chromatography and also tandem mass spectrometry microbiological or immunological (biochip) methods , as for anthelmintic and coccidistats tandem mass spectrometry has been used .2459 poultry samples were brought from slaughterhouse to detect authorized drugs while 2984 samples were brought from slaughterhouse and production facilities between January and December 2015 to detect prohibited substances ,as for the egg samples 557 were brought production facilities for detection of authorized substances while 69 samples brought to detect the prohibited substances ,sampling strategy used is according to targeting criteria Commission Decision 98/179/EC ,it is done by distribution of the samples by region on bases of last year production ,the result show that noncompliance rate in the samples for prohibited substances like nitrofuran was 0 % .As for the antibiotics used the result showed that the most poultry and egg used are marked free of residues .The strict regulation and application is well applied in production sector ,therefore a high level of safety is applied in Europe (Rudaut, B., & Fournet, I 2018).

Another study conducted for determination of sulfonamide in poultry boiler was done in Kenya specifically in peri urban Nairobi. This area contain a high number of chicken compared to other areas in Kenya, because of the poor hygiene practices used makes it necessary to use antimicrobial drug for infectious disease. Because sulfonamide is highly used for poultry production, therefore its detection is important in poultry meat. After collecting 90 broiler thigh samples and transporting them to the lab for analysis. Data analysis was done using excel and also chi square was used to identify the relation between withdrawal period of sulfonamide and level of acceptable MRL using insta+v3.36 ,chi square appears to be