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Tetracycline

Anti-Bacterial Agents
CATEGORIES

Anti-Bacterial Agents, Protein Synthesis Inhibitors, Antiprotozoal Agents, Tetracyclines


ALIASES

Alfaflor, Ambramicina, Anestesia Topica B. Braun, Anucet, Apocycclin, Bisolvomycin, Colircusi Anestetico, Drill, Economycin, Imex, Lubristesi, Muvito, Mysteclin Dermapharm, Nizfarm, Noacne, Nuvachten Depot, Oricyclin, Oxoferin, Pliaglis, Pylera, Rapydan, Resoborina Solucion, Hemofissural, Terricil, Tetracycline Actavis, Tetracycline Arena, Tetracycline ATB, Tetracycline Lainco, Tetracycline Nizfarm, Tetracykline Meda, Tetracycline Vision, Tetralysal, Vinciseptil


SUBSTANCES

tetracycline, tetracycline hydrochloride


ENVIRONMENTAL CONCERN: HIGH
Tetracycline is a broad spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria. It exerts a bacteriostatic effect on bacteria by binding reversible to the bacterial 30S ribosomal subunit and blocking incoming aminoacyl tRNA from binding to the ribosome acceptor site. It also binds to some extent to the bacterial 50S ribosomal subunit and may alter the cytoplasmic membrane causing intracellular components to leak from bacterial cells.

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HIGH

This substance is an antibiotic (also called, anti-bacterial agent). All antibiotics are suspected to cause antibiotic resistance and we should therefore try to limit releasing it to Nature via our wastewater streams.

Some key facts from WHO

  • Antibiotic resistance is one of the biggest threats to global health. food security, and development today
  • Antibiotic resistance can affect anyone, of any age, in any country.
  • Antibiotic resistance occurs naturally, but misuse of antibiotics in humans and animals is accelerating the process.
  • A growing number of infections – such as pneumonia, tuberculosis, gonorrhoea, and salmonellosis – are becoming harder to treat as the antibiotics used to treat them become less effective.
  • Antibiotic resistance leads to longer hospital stays, higher medical costs and increased mortality.
The T-value in the score for hazard refers to acute toxicity. Underlying data for P, B and T are from Fass.se, see below.

Concentrations of tetracycline in wastewater treatment plants is likely to select for bacterial resistance. Studies have shown that even low concentrations of antibiotics in the environment may contribute to antibiotic resistance and should therefore be taken to ensure that as little as possible end up in our environment.

Tetracycline is included in the Stockholm County Council's table of pharmaceuticals with risk for negative environmental impact according to the environmental program 2017-2021. Tetracycline has been detected in treated wastewater in Stockholm County in the last five years (2012-2016).

Below is Hazard and Risk from Fass environmental information for Tetracyklin Meda (tetracycline) (downloaded 2018-07-10)


Hazard
Persistence: "The inherent degradability of Tetracycline was determined in a combined test design based on the Zahn-Wellens test (OECD 302B, 1992) and the CO2-evolution test (OECD 301B, 1992). Tetracycline did not pass the criteria for inherent biodegradability as the test resulted in <70% degradation in 7 days."

Bioaccumulation: "Log P of -1,30 (unknown method)."

Acute toxicity: There are data for 2 trophic levels, lowest for cyanobacteria (Microcystis aeruginosa) 0.09 mg/L.

Risk
Sales data in Sweden are available for 2014. PEC/PNEC: "Since there are not sufficient data for the calculation of PNEC, the phrase “Risk of environmental impact of Tetracycline cannot be excluded, since there is not sufficient ecotoxicity data available” is used."

Suggestions on how to reduce the release of tetracycline
Concrete proposals on how to work to reduce emissions of environmentally harmful pharmaceuticals on the list have been developed in close cooperation with the Stockholm Drug and Therapeutics Committee's expert advice. The action proposals were developed from an environmental perspective. The patient's best always goes first and several pharmaceuticals on the list are also included in the Wise List. However, for such pharmaceuticals, there may be measures that could reduce the environmental impact.

Concrete proposal for tetracycline
• Tetracycline is not recommended in the Wise List. Note that lymphcycline, which is recommended in the Wise List, is rapidly hydrolyzed to active tetracycline in conjunction with absorption. Lymphcycline is recommended for moderate acne and moderate to severe rosacea.
• For antibiotics, the general rule is as restrictive use as possible without risking the patient's health. Relevant cultivations are important in order to choose antibiotics that have a good effect with as narrow spectrum as possible.

Comparative assessment of environmental risk and risk of resistance selection in human use of ivermectin, metronidazole, lymecycline and azelaic acid in Sweden (Report Goodpoint 2018)
The risk is clearly highest for lymecycline based on measured concentrations of tetracycline in uncleaned waste water that exceeds experimental established selective levels for antibiotic resistance in bacteria. A similar but lower risk profile exists for metronidazole based on total use but with significantly lower empirical support for the efficacy The topical use of metronidazole results in a negligible risk of resistance selection in waste water treatment plants. The risk of effects of human use of ivermectin is also low, given an expected contribution to exposure in aquatic environments at subnanogram levels, and a majority of efficacy studies that show significantly higher levels of efficacy. Since there is (at least) a study that reports effects at 1 pg/L, however, one can not completely rule out risk. For azelaic acid there is nothing that indicates an environmental hazard.

REFERENCES

  1. Gao, P., Y. Ding, H. Li and I. Xagoraraki (2012). Occurrence of pharmaceuticals in a municipal wastewater treatment plant: Mass balance and removal processes. Chemosphere 88, 17-24.l
  2. Yang, S., Cha, J., and Carlson, K., (2005). Simultaneous extraction and analysis of 11 tetracycline and sulfonamide antibiotics in influent and effluent domestic wastewater by solid-phase extraction and liquid chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr A 1097, 40-53.
  3. Yang, X., R. C. Flowers, H. S. Weinberg and P. C. Singer (2011). Occurrence and removal of pharmaceuticals and personal care products (PPCPs) in an advanced wastewater reclamation plant. Water Res 45, 5218-5228.
  4. Sungpyo, K., Aga, D., (2007), Potential Ecological and Human Health Impacts of Antibiotics and Antibiotic-Resistant Bacteria from Wastewater Treatment Plants, Toxicol. Environ. Health Part B, 559-573
  5. Nunes, B., Antunes, S.C., Gomes, R. Campos, J., Braga, M., Ramos A, Correia, A., (2015), Acute Effects of Tetracycline Exposure in the Freshwater Fish Gambusia holbrooki: Antioxidant Effects, Neurotoxicity and Histological Alterations, Arch Environ Contam Toxicol 68, 371
  6. Zhang, Q., Cheng, J. & Xin, Q. (2015), Effects of tetracycline on developmental toxicity and molecular responses in zebrafish (Danio rerio) embryos, Ecotoxicology 24, 707.
  7. Yang, L. , Ying, G. , Su, H. , Stauber, J. L., Adams, M. S. and Binet, M. T. (2008), Growth‐inhibiting effects of 12 antibacterial agents and their mixtures on the freshwater microalga Pseudokirchneriella subcapitata. Environ Toxicol Chem 27, 1201-1208
  8. Goodpoint. Prioritering av läkemedel med miljörisk inom SLL. Stockholm: Goodpoint; 2016. Rapport LS 2016–0634.
  9. IVL Swedish Environmental Research Institute Ltd. Fick J, Lindberg RH, Kaj L, Brorström-Lundén E. Results from the Swedish National Screening Programme 2010. Subreport 3. Pharmaceuticals.
  10. IVL Swedish Environmental Research Institute Ltd Fick J, Lindberg RH, Fång J, Magnér J, Kaj L, Brorström-Lundén E. Screening 2014. Analysis of pharmaceuticals and hormones in samples from WWTPs and receiving waters. Rapport C 135.
  11. Backhaus T, Froehner K, Altenburger R, Grimme LH. Toxicity testing with Vibrio Fischeri: A comparison between the long term (24 h) and the short term (30 min) bioassay. Chemosphere. 1997;35(12):2925-2938.
  12. Bengtsson-Palme J, Larsson DG. Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation. Environ Int. 2016;86:140-9.
  13. Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 2011;7:e1002158.
  14. SLL. Sammanställning av läkemedelsprovtagningar - Bearbetning av regional försäljningsstatistik av läkemedel samt datamaterial från Stockholms läns landstings mätprogram för läkemedelssubstanser i vattenmiljö, 2012–2016.
  15. Stockholms läns landsting. Förteckning över miljöbelastande läkemedel med åtgärdsförslag framtagen inom ramen för SLL:s miljöprogram 2017–2021.
  16. Goodpoint. Jämförande bedömning av miljörisk och risk för resistensselektion vid human användning av ivermektin, metronidazol, lymecyklin och azelinsyra. Stockholm: Goodpoint; 2018.