Dr. Iris G. Udasin-Professor Occupational Medicine Director of
Employee Health Rutgers Robert Wood Johnson Medical School Regional
Occupational Medicine Conference October 18, 2014
Slide 2
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?
Slide 3
Types of Hazards Physical Biologic Chemical Locations of
Hazards Pharmacy Animal Care Facility Pathology Environmental
Services
Slide 4
Genotoxicity Carcinogenicity Teratogenicity of fertility
impairment Serious organ or other toxic manifestation at low doses
in experimental animals or treated patients
Slide 5
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
Slide 6
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
Slide 7
Animal care takers / technicians Scientists Veterinarians
Physicians Graduate Students
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
Slide 10
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
Slide 11
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, Streptobacillus maniliformis (may use Augmentin
or Doxy, anti rabies not indicated, less likely infection) JAVA MA,
Dec 2010
Slide 12
Lifting heavy animals, food bags, cages associated with back
injuries Cumulative trauma/repetitive motion may result in carpal
tunnel syndrome, tennis elbow, bursitis
Viral Rickettsial Bacterial Fungal Protozoans 868 of 1415 (61%)
of known human pathogens are zoonotic, 50 are clinically important
in US
Slide 15
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
Slide 16
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
Slide 17
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
Slide 18
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
Slide 19
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 Glueck, J.
AALAS 2012
Slide 20
Risk of allergic reactions to Risk Group Historylaboratory
animals___________Comments NormalNo evidence of 10% 90% of normal
group will allergic disease never develop symptoms in spite of
repeated animal contact AtopicPre-existing allergic Up to 73%
Workers who become disease sensitized to animal proteins will
eventually develop symptoms on exposure AsymptomaticImmunoglobulin
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
Medical history Physical examination Work practices Personal
protective equipment Allergy screening/evaluation Zoonosis
surveillance
Slide 24
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
Slide 25
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
Slide 26
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 Clin Immunol, August, 2001
Slide 27
Gloves Lab coats Particulate respirator with face shields
Slide 28
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
Slide 29
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
Slide 30
Confirm diagnosis by presence of IgE antibodies to allergen in
question (best done by RAST) PFTs to assess asthma severity
Exposure reduction/avoidance best treatment Immunotherapy against
dog and cat allergens somewhat successful Best strategy is
prevention!
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
Slide 36
Skin Mucous Membrane Respiratory Cancer Reproductive
Slide 37
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
Slide 38
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
Slide 39
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
Slide 40
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
Slide 41
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
Slide 42
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
Slide 43
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
Slide 44
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
Slide 45
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
Slide 46
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