Cytotoxic Drug Safety - Minimising the risk to veterinary staff and clients

Policy

1. The use of cytotoxic chemotherapy agents in veterinary practice must occur in a way which avoids harm to the personnel potentially exposed to the drugs, including veterinary practice staff and animal owners.
2. Use of cytotoxic chemotherapy agents must be compliant with occupational health and safety requirements.

Purpose

The purpose of this policy is to minimize potential harm to personnel who may be exposed to chemotherapeutic drugs, including veterinary practice staff and animal owners.

Background

The use of cytotoxic chemotherapy agents in veterinary practice is increasing and poses an exposure risk to humans, both in the workplace and at the patient’s home. The handling of cytotoxic chemotherapy agents has been classified as an occupational health and safety hazard due to the potential of these drugs to increase the risk of stillbirth in addition to their being mutagenic, carcinogenic and teratogenic in nature.^1-7 Small molecule inhibitors, newly available for veterinary treatment, carry similar risks as they are anti-angiogenic agents, which could also harm a growing foetus.³⁴ The recommendation is that these agents should be handled in the same manner as other cytotoxic chemotherapy agents.

Personnel who may be potentially exposed to these drugs during and following use include the veterinarians, veterinary nurses and technicians, cleaners, animal attendants and pet owners.

Risks to veterinary practice staff

There is little information available regarding the rate of exposure of veterinary personnel to cytotoxic chemotherapy agents and the short- and long-term consequences of this. Limited early studies found that frequent contamination of personal protective equipment (gloves) and the veterinary clinic environment (door handles, administration areas, floors) occurred. In two studies, compliance with safety procedures was documented at a level of only 60-70%.^8,9 In more recent studies, there has been a marked reduction in contamination found in hospitals that have implemented strict engineering controls (biological safety cabinet) in addition to supplemental controls (closed system transfer devices) for intravenous chemotherapy, however, contamination is still detected with oral chemotherapy drugs. ^9,10

Human studies have found that health care workers handling chemotherapy agents have increased chromosomal aberrations in addition to urinary excretion of the chemotherapy agents and their metabolites. ^11-20 Some larger studies have found an incrementally increased risk of infertility and miscarriage with occupational exposure to chemotherapy agents.^4,21-23 Alkylating agents are associated with the highest number of abnormalities, at a frequency which increases with the amount of exposure. Constant exposure, even at low doses, can increase the risk of some cancers developing.^24,25 Based on these studies, there is concern that the risk to veterinary staff may be similar. ^11,12

Risks to pet owners

There is currently no information defining the risk to clients that care for their pets undergoing cytotoxic chemotherapy treatment. However, precautions should be taken by clients whose pets are undergoing chemotherapy whether they are receiving the drugs at the veterinary practice or at home, as there is potential for exposure of family members to contaminants.²⁶ Contamination of the environment has been reported as a result of people receiving chemotherapy ^27,28, so it is therefore reasonable to assume that a similar risk of environmental contamination will occur when treating animals with chemotherapy.

Known clearance levels

In veterinary oncology, chemotherapy is often performed on an outpatient basis. As there may be residue presence in canine urine, faeces and other bodily fluids, owners are at risk of exposure to cytotoxic drugs through these media. The following table ^30-32 gives values for the cytotoxic drug residues in urine and serum of dogs receiving anticancer chemotherapy. There are currently no studies for cytotoxic residue in the faeces of dogs.

DRUGS – Veterinary Clearance

There is also one recent study that reveals detectable levels of carboplatin, a cytotoxic chemotherapy agent in the sebum and cerumen of dogs. ³³

Guidelines

Exposure to cytotoxic chemotherapy agents and clinical waste can occur if control measures fail.²⁹ AVA Guidelines have been developed to assist in minimising the risks of exposure to cytotoxic chemotherapy agents, managing chemotherapy waste materials, managing potential exposures, and best practice protocols for the veterinary hospital and the animal’s home.

References

1. Lucroy MD. Chemotherapy safety in veterinary practice: hazardous drug preparation. Comp Cont Ed Pract Vet. 2001; 23:6.
2. Lucroy MD. Chemotherapy in veterinary practice: hazardous drug administration. Comp Cont Ed Pract Vet. 2002;24:7.
3. MacDonald V. Chemotherapy: managing side effects and safe handling. Can Vet J. 2009;50:4.
4. Valanis B, Vollmer WM, Steele P. Occupational exposure to antineoplastic agents: self‐reported miscarriages and stillbirths among nurses and pharmacists. J Occup Environ Med. 1999;41:632.
5. Autio K, Rassnick KM, Bedford‐Guaus SJ. Chemotherapy during pregnancy: a review of the literature. Vet Comp Oncol. 2007;5:61–75.
6. Ebert U, Löffler H, Kirch W. Cytotoxic therapy and pregnancy. Pharmacol Ther. 1997;74:207–220.
7. Sessink PJM, Kroese ED, van Kranen HJ, Bos RP. Cancer risk assessment for health care workers occupationally exposed to cyclophosphamide. Int Arch Occup Environ Heath. 1995;67:317–323.
8. Meijster T, Fransman W, Veldhof R, Kromhout H. Exposure to antineoplastic drugs outside the hospital environment. Ann Occup Hyg. 2006;50:657–664.
9. Couch J, Gibbins J, Connor TH. Evaluation of chemotherapy drug exposure at a veterinary teaching hospital in Michigan. J Occup Environ Hyg. 2013;10:D45–D51.
10. Alexander K, Northrup N, Clarke D, et al. Engineering controls in veterinary oncology: A survey of 148 ACVIM board certified oncologists and environmental surveillance in 20 speciality hospitals. 2018. Vet Comp Oncol. 2018 Sep; 16(3):385-391.
11. Kopjar N, Kašuba V, Rozgaj R, et al. The genotoxic risk in health care workers occupationally exposed to cytotoxic drugs—a comprehensive evaluation by the SCE assay. J Environ Sci Health Part A: Toxic/Haz Subst Environ Eng. 2009;44:462–479.
12. McDiarmid MA, Oliver MS, Roth TS, Rogers BEC. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med. 2010;52:1028–1034. PMid:20881619
13. Villarini M, Dominici L, Piccinini R. Assessment of primary, oxidative and excision repaired DNA damage in hospital personnel handling antineoplastic drugs. Mutagenesis. 2011;26:359–369.
14. Ursini CL, Cavallo D, Colombi A. Evaluation of early DNA damage in healthcare workers handling antineoplastic drugs. Int Arch Occup Environ Health. 2006;80:134–140.
15. Rekhadevi PV, Sailaja N, Chandrasekhar M, et al. Genotoxicity assessment in oncology nurses handling anti‐neoplastic drugs. Mutagenesis. 2007;22:395–401.
16. Sasaki M, Dakeishi M, Hoshi S, et al. Assessment of DNA damage in Japanese nurses handling antineoplastic drugs by the comet assay. J Occup Health. 2008;50:7–12.
17. Burgaz S, Karahalil B, Canli Z, et al. Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations. Hum Exp Toxicol. 2002;21:129–135.
18. Jakab MG, Major J, Tompa A. Follow‐up genotoxicological monitoring of nurses handling antineoplastic drugs. J Toxicol Environ Health Part A. 2001;62:307–318.
19. Falck K, Grohn P, Sorsa M, et al. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet. 1979;313:1250–1251.
20. Sessink PJ, Boer KA, Scheefhals AP, et al. Occupational exposure to antineoplastic agents at several departments in a hospital. Environmental contamination and excretion of cyclophosphamide and ifosfamide in urine of exposed workers. Int Arch Occup Environ Health. 1992;64:105–112.
21. Selevan SG, Lindbohm ML, Hornung RW, Hemminki K. A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med. 1985;313:1173–1178.
22. Stucker I, Caillard JF, Collin R, et al. Risk of spontaneous abortion among nurses handling antineoplastic drugs. Scand J Work Environ Health. 1990;16:102–107.
23. Dranitsaris GJ, Poirier M Schueller S T, et al. Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta‐analysis of the literature. J Oncol Pharm Pract. 2005;11:69–78
24. Skov T, Maarup B, Olsen J, et al. Leukaemia and reproductive outcome among nurses handling antineoplastic drugs. Br J Ind Med. 1992;49:855–861.
25. Gunnarsdottir HK, Aspelund T, Karlsson T, Rafnsson V. Occupational risk factors for breast cancer among nurses. Int J Occup Environ Health. 1997;3:254–258
26. ECVIM . In: Animals ECoVIMoC, ed. Preventing Occupational and Environmental Exposure to Cytotoxic Drugs in Veterinary Medicine. Europe: ECVIM; 2007:31.
27. Yuki M, Takase K, Sekine S, Ishida T. Evaluation of surface contamination with cyclophosphamide in the home setting of outpatients on cancer chemotherapy. J Nurs Educ Pract. 2014;4:16–23.
28. Janssens T. Antineoplastic drugs in veterinary oncology: excretion in dogs, contamination of the environment and exposure assessment of people at risk [Doctoral thesis]. The Netherlands: Utrecht University; 2012:10‐05.
29. Klahn S. Chemotherapy safety in clinical veterinary oncology. Vet Clin North Am Small Anim Pract. 2014;44:941–964
30. Smith AN, Klahn S, Phillips B, et al. ACVIM small animal consensus statement on safe use of cytotoxic chemotherapeutics in veterinary practice. J Vet Intern Med. 2018 May-Jun; 32(3): 904–913
31. Knobloch A, Mohring SA, Eberle N, et al. Cytotoxic drug residues in urine of dogs receiving anticancer chemotherapy. J Vet Intern Med. 2010 Mar-Apr; 24(2):384-90
32. Knobloch1, S.A.I. Mohring1, N. Eberle, et al. Drug residues in serum of dogs receiving anticancer chemotherapy. J Vet Intern Med. 2010. 24:379-383.
33. Janssens T, Brouwers EE, de Vos JP, et al. Determination of platinum originating from carboplatin in canine sebum and cerumen by inductively coupled plasma mass spectometry. J Pharm Biomed Anal. 2011 Jan; 54(2):395-400.
34. https://www.zoetisus.com/products/dogs/palladia/index.aspx

Date of ratification by AVA Board 5 November 2021