Non- Infectious Exposures in the Academic Medical Center

1. Non- Infectious Exposures in the Academic Medical Center Dr. Iris G. Udasin-Professor Occupational Medicine Director of Employee Health Rutgers – Robert Wood Johnson Medical School Regional Occupational Medicine Conference October 18, 2014

2. Regional Occupational Medicine Conference October 18, 2014 Goals and Objectives • Understand the non-infectious exposures which occur in performing health care in research institutes • Be able to design effective surveillance programs to minimize the effects of exposures • Identify and implement safe and effective cleaning products to minimize exposures • Incorporate flexibility in order to train new health professionals and stimulate new research ideas Review Question • What are the best strategies to minimize animal allergy? • What prevention and treatment is available for workers exposed to irritants, allergens, and potential carcinogens in the academic medical center?

3. Types and Locations of Hazards Types of Hazards • Physical • Biologic • Chemical Locations of Hazards • Pharmacy • Animal Care Facility • Pathology • Environmental Services

4. Pharmacy: Categorization of Drugs as Hazardous Genotoxicity Carcinogenicity Teratogenicity of fertility impairment Serious organ or other toxic manifestation at low doses in experimental animals or treated patients

5. Work Areas of Concern for Exposure to Hazardous Drugs • Pharmacy or other preparation area • Withdrawal of needles from vials • Transfer using syringes • Breaking open of ampules • During reconstitution of powdered or lyophilized drugs • Administration of drugs to patients • Injection into IV line • Disposal of drugs and contaminated materials • When aerosoles generated in administration of drugs • Cleaning/bedding changes after • More exposure in the animal care research facility than patient care areas

6. Preparation of Hazardous Drugs • Area should have restricted access • Prepare in ventilated cabinets • Use NIOSH certified respirators when ventilation inadequate • Use 2 pairs powder-free disposable gloves covering gown cuff • Wear disposable gowns, face shields • Use safety syringes and triple lumen catheters • Disposal as hazardous waste and decontaminate work area • Review MSDS NIOSH 2004

7. LABORATORY ANIMAL WORKERS • Animal care takers / technicians • Scientists • Veterinarians • Physicians • Graduate Students

8. Physical Hazards Animal bites, scratches, kicks Sharps Flammable materials Electricity UV Lasers Ionizing Radiation Housekeeping ERGONOMICS Noise

9. Animal Bite, Scratches, KicksAnd Related Hazards • Animals may become frightened by sounds (high pitched) and smells • Inappropriate handling may cause discomfort, pain and distress • Restraint is an important issue with large dogs and non-human primates • In general population, bites most common in dogs, rats and rodents are second and third • In laboratories, rodent bites most common • During their careers, approximately 2/3 veterinarians report a major animal related injury resulting in lost time or hospitalization

10. Clinical Features of Bite Wounds Avulsions – skin torn away from underlying tissues and bone Lacerations – tears in skin Punctures – animal teeth penetrating skin and underling structure Dog bites most likely avulsions and lacerations Cat bites most likely punctures Ferret bites cause punctures Bats unlikely to cause tissue damage Cat bites hands most likely to cause severe injury

11. Treatment Of Bites Ascertain rabies status of the laboratory animal Update tetanus in exposed workers Consider antibiotic therapy, especially in dog and cats Dog: P, canis, S.Aureus – Augmentin (3-18% become infected) Cat: P. multicida, S.Aureus – Augmentin (28-80% become infected) Rat: Spirillium minus, Streptobacillusmaniliformis (may use Augmentin or Doxy, anti rabies not indicated, less likely infection) JAVA MA, Dec 2010

12. Ergonomic Hazards Lifting heavy animals, food bags, cages associated with back injuries Cumulative trauma/repetitive motion may result in carpal tunnel syndrome, tennis elbow, bursitis

13. Chemical Hazards Cleaning agents/disinfectants Pharmacologic agents Anesthetic gases Preservatives Pesticides (control fleas, tick, insects)

14. Infectious Agents / Zoonoses Viral Rickettsial Bacterial Fungal Protozoans 868 of 1415 (61%) of known human pathogens are zoonotic, 50 are clinically important in US

15. Viral Diseases B Virus Infection (cercopithecine herpes virus) Ebola virus (mainly non-human primates) Marburg (direct contact with tissues) Hantavirus (wild rodents, transmitted through inhalation of infectious aerosols) Lymphocytic choriomeningitis virus occurs naturally in mice, hamsters, guinea pigs, non-human primates, swine, dogs; transmitted by accidental inoculation, inhalation, contamination of mucous membranes Pox virus Orf Disease (sheeps and goats, transmitted by direct contact) Measles - Hepatitis A, B, C, D, E, Simian Immune Deficiency Virus, Influenza, Arbovirus, rabies* Rabies

16. Laboratory Animal Allergy 10-44% of exposed workers develop allergic symptoms 10% have occupational asthma 73% of people with pre-existing allergies develop LAA Symptoms evolves over 1-2 years usually manifested by nasal symptoms, itchy eyes, rashes The majority of animal allergens belong to the lipocalin protein family and are small proteins Animal allergens are produced in the liver and secretor's glands and localize in animal fluids including urine, saliva, blood, milk, and sweat. Zahradnik, Frontiers in Immunology, 2014

17. Laboratory Animals and Respiratory Allergies: The Prevalence of Allergies among Laboratory Animal Workers and the Need for Prophylaxis Case control of animal handlers and non animal handlers at two Brazilian Universities given questionnaires, spirometry, bronchial challenge test, and a skin prick tests for 11 common allergens and 5 occupational allergens (rat, mouse, guinea pig, hamster, and rabbit) 455 animal handlers and 387 controls Sensitization to occupational and animal allergens was higher (16%) compared to (30%) in non-handlers While 85% of employees had access to PPE, only 19% reported that they used it Only 25% of employees report receiving orientation prior to working with animals Individual advice to workers is an important preventive activity prior to working with animals Ferraz, Clinics (Sao Paulo),2013

18. Jobs with Greatest of Developing LAA Cage cleaning Disposal of filters in animal rooms Changing of filters in animal rooms Direct handling of animals including blood collection and weighing Surgical procedures Euthanasia Working in concentrated animal operations Huerkamp 2009

19. Exposure of Laboratory Animal Care Workers Airborne Mouse and Allergens Glueck, J. AALAS 2012 Personal breathing zone, dust samples obtained from 7 workers to assess which activities were associated with higher levels of exposure (mice and rat allergens were studied) Washing and cleaning cages, handling mice most important determining exposure

20. Risk of Developing Allergy to Laboratory Animals Risk of allergic reactions to Risk Group History laboratory animals___________Comments Normal No evidence of 10% 90% of normal group will allergic disease never develop symptoms in spite of repeated animal contact Atopic Pre-existing allergic Up to 73% Workers who become disease sensitized to animal proteins will eventually develop symptoms on exposure Asymptomatic Immunoglobulin E Up to 100% Risk of developing allergic symptoms of rhinitis, asthmas, or contact urticaria with continued exposure is high Symptomatic Clinical symptoms 100% 33% with chest on exposure to allergic symptoms; 10% of group animal proteins might develop occupational asthma; even minimal exposure can lead to permanent impairment

21. Allergic Reactions to Laboratory-Animal Allergens Disorder Symptoms Signs Contact urticaria Redness, itchiness of skin, welts Raised, circumscribed hives erythematous lesions Allergic conjunctivitis Sneezing, itchiness, clear Conjunctival vascular nasal dainage, nasal congestion engorgement, cheminosis , clear discharge (usually bilateral) Allergic rhinitis Sneezing, itchiness, clear nasal Pale or edematous nasal drainage, nasal congestion mucosa, clear rhinorrhea Asthma Cough, wheezing, chest tightness Decreased breath shortness of breath sounds, prolonged exirpatory phase or wheezing, reversible airflow obstruction, airway hyperresonsiveness Anaphylaxis Generalized itching, hives, Flushing, urticaria, throat tightness, eye or lip swelling, angioedemastridor, difficulty in swallowing, hoarseness, hypotension shortness of breath, dizziness, fainting, nausea, vomiting, abdominal cramps, diarrhea

22. Specific Animals Than Can Provoke Allergic Reactions Rats Mice Guinea Pigs Gerbils Rabbits Cats Dogs

23. Preventive Measures Medical history Physical examination Work practices Personal protective equipment Allergy screening/evaluation Zoonosis surveillance

24. Work Practices To Avoid LAA Perform animal manipulation in ventilated hood/safety cabinet Avoid wearing street clothes while working with animals Leave work clothes at the work place to avoid potential exposure problems for family members Keep cages and animal areas clean

25. Engineering Controls Hood or biologic safety cabinet Modify ventilation/filtration systems *increase ventilation and humidity in animal housing areas *ventilate animal housing/handling areas separate from rest of facility *direct airflow away from workers *install ventilated animal cage racks

26. Elimination Of Mouse Allergens by Using Individually Ventilated Cage Systems And Ventilated Cabinets No mouse urinary protein (MVP) detected when cleaning done in ventilated cabinet Allergen exposure minimized if mice are housed in individually ventilated cages or when “sealed” with positive pressure Fisher J, Allergy ClinImmunol, August, 2001

27. Personal Protective Equipment Gloves Lab coats Particulate respirator with face shields

28. Medical Surveillance/Monitoring Occupational/medical history to identify early symptoms of LAA (sneezing, runny nose, chest tightness, wheezing cough, SOB) Physical examination Spirometry Skin/RAST testing Prevention or early diagnosis of LAA or occupational asthma

29. Atopy Indicators Family history of allergy in parents, siblings or children Previous allergy in childhood or adulthood Positive skin prick tests against non-animal environmental allergens (ie. dust, mites, mold) Cat and dog allergy are important risk factors for LAA

30. Evaluation Of The Allergic Worker Confirm diagnosis by presence of IgE antibodies to allergen in question (best done by RAST) PFT’s to assess asthma severity Exposure reduction/avoidance best treatment Immunotherapy against dog and cat allergens somewhat successful Best strategy is prevention!

31. The Pathology Department

32. Cryostat Blade: Ultimate Physical Hazard

33. Chemical Exposure in Pathologist FORMALDEHYDE Xylene Toluene

34. Formalin Composition: Toxicology Data on Ingredients: Formaldehyde: ORAL(LD50): Acute: 100 mg/kg [Mouse]. 260 mg/kg [Guinea pig]. MIST (LC50): Acute: 454000 mg/m 4 hours [Mouse]. Methyl alcohol: ORAL (LD50): Acute: 5628 mg/kg [Rat]. DERMAL (LD50): Acute: 15800 mg/kg [Rabbit]. VAPOR (LC50): Acute: 64000 ppm 4 hours [Rat].

35. Indicators of Exposure to Formaldehyde Most accurate is to measure concentration of formaldehyde gas in air surrounding the water 8 hour time weight average (TWA) and short term exposure limit (STEL) in badges worn by workers Because formaldehyde is rapidly metabolized, measurement in blood and urine is extremely unreliable Some evidence that formaldehyde reacts with cell components including nucleic acids, proteins, and glutathione Some evidence of abnormal levels of non-specific markers of damage including DNA protein cross links, adducts, and sister chromatid exchange

36. Potential Health Consequences of Formaldehyde Exposure Skin Mucous Membrane Respiratory Cancer Reproductive

37. Dermal Effects Acute skin irritation in everyone at sufficient concentration (drying, scaling, cracking) Causes allergic contact dermatitis with cell mediated hypersensitivity in some patients (eczematous dermatitis or hives) In 6 out of 15 patients with positive patch tests, only 2 demonstrated IgE response Required direct skin contact (ie cosmetics) and is extremely unlikely when wearing gloves All monitoring not useful in monitoring skin exposures Linden Allergy 1993

38. Mucus Membrane Irritation Formaldehyde known irritant of upper respiratory tract and eyes Produces histological changes in nasal mucosa associated with loss of cilia, goblet cell hyperplasia, and squamous metaplasia based on studies of manufacturing workers Increased micronuclei of buccal cell smears in mortuary students

39. Formaldehyde and Chemosensory Irritation in Humans: A Controlled Exposure Study Testing conducted in 21 health volunteers over a 10 week period Subject exposed to varying concentrations of formaldehyde and during 4 to 10 exposure sessions, ethyl acetate used as masking agent Measurements consisted of conjunctival redness, blinking frequency, nasal flow and resistance, pulmonary function and reaction times No significant exposures effects on nasal flow and resistance, pulmonary function, or reaction times Blinking frequency and conjunctival redness were significantly increased by short term exposures of 0.5-1.0 PPM Eye and olfactory symptoms at 0.3 PPM Nasal irritation at 0.5 PPM but when combined with ethyl acetate seen as low as 0.3 PPM Eye irritation most sensitive indicator of exposure Long, Regul Toxicol Pharm 2008

40. Pulmonary Effects of Exposure to Formaldehyde Mechanism of respiratory effects is usually irritation but may cause allergy Reversible broncho-constriction rarely occurs at levels below 3 PPM In sufficient quantities can cause pulmonary edema Hypothesis that low level formaldehyde exposure may increase risk of allergic sensitization NJ DOH 2009

41. Short Term Effects of Formaldehyde on Peak Expiratory Flow and Irritant Symptoms Medical students were exposed to 1.1 PPM while dissecting cadavers for 2.5 hours per week Increased nose, throat, and eye irritation Reduced peak flow reported during time in laboratory Effect diminished after 4 weeks of exposure Krakowiak Am J Ind Med 1998

42. Non-Cancer Effects of Formaldehyde and Relevance for Setting Indoor Air Guidelines: National Research Center for the Working Environment Eye most sensitive organ, effects are at lower levels than odor threshold Numerous studies demonstrate eye irritation at 0.3-0.5 PPM Dose response relationship not seen in humans at levels lower than 1 PPM This panel recommends an indoor air guideline of 0.1 PPM as protective against health effects Wolkoff Environ Int 2010

43. Reproductive and Developmental Toxicity Limited evidence of reproductive toxicity in occupational cohort Case control showed increase in spontaneous abortion in women working in Finnish laboratories but they also had significant exposure to xylene One study of cosmetologist with excess spontaneous abortions Numerous negative studies Animal studies in rodents did not show adverse reproductive effects in rodents exposed to formaldehyde by inhalation, ingestion, or skin contact Baker

44. The Cancer Issues: • The International Agency for research on cancer has classified formaldehyde as a Group 1 human carcinogen based on sufficient evidence that formaldehyde causes nasopharyngeal cancer and leukemia Bean Lancet Oncol 2009

45. Inhaled Formaldehyde: Evaluation of Sensory Irritation in Relation to Carcinogenicity Critical health effects of formaldehyde exposure include sensory irritation and the potential to induce tumors of the nasal and respiratory tract Review of human and animal literature indicates that the levels of formaldehyde that induce nasal tumors in experimental animals are at least an order of magnitude higher than levels known to cause irritation Arts J Regul Toxicol Pharm 2010

46. Exposure Limits on Formaldehyde NTP, US EPA suggest irritation not most sensitive toxic endpoint Exposure limit of oil ppm should protect a susceptible people Engineering controls and improved work practices important in prevention Golden, Critical Review in Toxicology, 2011

47. Chemical Disinfectants And PotentialHealth Effects • Isopropyl Alcohol • Sodium Hypochlorite • Iodine • Phenol • Quaternary Ammonium Compounds • Formaldehyde • Glutaraldehyde • Ethlyene Oxide • 2 butoxyethanol • Ethanolamines Irritant Irritant, Burns Irritant, Burns Irritant, Skin Necrosis Contact Dermatitis Irritant, Sensitizer, Mutagen, Carcinogen Irritant, Sensitizer Irritant, Chemical Burns, Reproductive Toxin, Carcinogen Bello, Environ Health 2009

48. Questions udasin@eohsi.rutgers.edu