Ethylene Oxide- Building Awareness for Primary Care Physicians - PowerPoint PPT Presentation

Ethylene Oxide- Building Awareness for Primary Care Physicians & Other Clinicians Advocate Condell Medical Center Libertyville, IL May 7, 2019

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Accreditation & Disclosures Accreditation The Illinois Academy of Family Physicians (IAFP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Webinar Credit Designation:| AMA PRA Category 1 - The Illinois Academy of Family Physicians Network designates this live activity for a maximum of 1.00 AMA PRA Category 1 credit™. Online Enduring Credit Designation: AMA PRA Category 1 - The Illinois Academy of Family Physicians designates this online enduring material for a maximum of 1.00 AMA PRA Category 1 credit™. Faculty Disclosure Statement The Illinois Academy of Family Physicians adheres to the conflict of interest policy of the ACCME and the AMA. It is the policy of Illinois AFP to ensure balance, independence, objectivity, and scientific rigor in all its educational activities. All individuals in a position to control the content in our programs are expected to disclose any relationships they may have with commercial companies whose products or Services may be mentioned so that participants may evaluate the objectivity of the presentations. In addition, any discussion of off-label, experimental, or investigational use of drugs or devices will be disclosed by the faculty. Only those participants who have no conflict of interest or who agree to an identified resolution process prior to their participation were involved in the CME activity. Speaker & Faculty Disclosures Sana Ahmed, MD; Mark Johnson, PhD; Susan Buchanan MD, MPH; Aditi Vyas, MD; Kyle Garner, MPH; and Vincent Keenan, MSPH (IAFP Staff) disclosed no relevant financial relationship or interest with a proprietary entity producing, marketing, reselling or distributing health care goods or services. This program does not include any discussion or demonstration of any pharmaceuticals or medical devices that are not approved by the Food and Drug Administration (FDA) or that are considered “off-label.” 3

Ethylene Oxide Webinar Moderator: Sana Shireen Ahmed, MD Medical Epidemiologist Lake County Health Department and Community Health Center Speakers: Aditi Vyas, MD, MS Occupational & Environmental Medicine , Resident University of Illinois Hospital and Health Sciences System Mark Johnson, MSPH, PhD, DABT Regional Director/Toxicologist, Agency for Toxic Substances and Disease Registry (ATSDR), Centers for Disease Control and Prevention Kyle Garner, MPH Cancer Epidemiologist Illinois State Cancer Registry, Illinois Department of Public Health Susan Buchanan, MD, MPH, D-ABFM, D-ABPM-OM Associate Director, Occupational & Environmental Medicine Residency University of Illinois Hospital and Health Sciences System 4

Outline- Ethylene Oxide (EtO) Welcome and Introductions  Background- Uses of EtO; How are people exposed to EtO  Summary of EtO Toxicology  Cancer risks associated with EtO- epidemiologic studies  Summary of ATSDR evaluation of Sterigenics Facility- Willowbrook  Overview of Air Monitoring Plan for Lake County facilities  IDPH review of cancer incidence in Willowbrook area and beyond  What can healthcare providers do?  Action items for patients- “Aggressive self-monitoring”  Medical referral resources  5

EtO- Chemical Structure 6

Background Information- EtO  Most EtO used for precursor for industrial chemicals (e.g., ethylene glycol), plastics, PVC pipes  Less than 1% used for sterilization of medical equipment, consumer products, certain foods (e.g., spices) that can’t be steam sterilized  Used as a fumigant for some agricultural products IARC Monograph- Ethylene Oxide https://monographs.iarc.fr/wp-content/uploads/2018/06/mono100F-28.pdf 7

"A Comparison of Gamma, E-beam, X-ray and Ethylene Oxide Technology for the Industrial Sterilization of Medical Devices and Healthcare Products," Gamma Industry Processing Alliance, Aug 31, 2017. 8

EtO Background Physical properties: High Vapor Pressure- gas at 20 0 C  Colorless, tasteless vapor  Odor-threshold is 500 ppm  Sweet, ether-like odor  Flammable, explosive  Reacts with water, strong acids, alkalis, and oxidizers  Atmospheric persistence: 50-60 day half-life; degrades to  hydroxyl radicals National Library of Medicine- Toxnet. https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~7WUNLz:1 ATSDR. Medical Management Guidelines for Ethylene Oxide. https://www.atsdr.cdc.gov/mmg/mmg.asp?id=730&tid=133 9

Mechanism of EtO Toxicity  Very potent alkylating agent  Forms protein and DNA adducts  Mutagenic- chromosomal aberrations  Carcinogenic -International Agency for Research on Cancer (IARC) “Carcinogenic to Humans” -National Toxicology Program (NTP) /DHHS “Known to be a Human Carcinogen” -Environmental Protection Agency (EPA) “Known Human Carcinogen” USEPA. Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/1025tr.pdf 10

How long does EtO stay in the body?  Physiological half life: 45-60 minutes  Exhaled as EtO or metabolized and excreted in urine  Completely eliminated 1-2 days after exposure has ended National Library of Medicine- Toxnet. https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~7WUNLz:1 11

Routes of exposures to EtO  Inhalation – most likely exposure pathway, due to high vapor pressure  Dermal- liquid EtO 12

EtO Risk Assessment 13

Occupational High Level EtO Exposure - Acute Respiratory Effects • Mucous membrane irritant, bronchospasm • Immediate local irritation of the skin, eyes, and upper respiratory tract • Exposure to high concentrations can cause immediate or delayed pulmonary edema • May result in sensitization response ATSDR. Medical Management Guidelines for Ethylene Oxide. https://www.atsdr.cdc.gov/mmg/mmg.asp?id=730&tid=133 14

Occupational High Level EtO Exposure - Acute CNS Effects  CNS depressant  Seizures, loss of consciousness, coma  Neurological signs and symptoms may be delayed 6 hours or more after exposure  Exposure to high concentrations can lead to respiratory paralysis and delayed peripheral nerve damage ATSDR. Medical Management Guidelines for Ethylene Oxide. https://www.atsdr.cdc.gov/mmg/mmg.asp?id=730&tid=133 15

Occupational High Level EtO Exposure -Other Acute Effects  Nausea and vomiting-often delayed  Severe cases  Renal damage  Cyanosis  Direct skin contact: frostbite can occur due to rapid evaporation and consequent cooling ATSDR. Medical Management Guidelines for Ethylene Oxide. https://www.atsdr.cdc.gov/mmg/mmg.asp?id=730&tid=133 16

Occupational High Level EtO Exposure - Chronic Health Effects • Cancer • Reproductive effects, fetal effects • Impaired cognitive function, seizures • Damage to liver and kidneys • Skin allergy • Cataracts and corneal burns • Peripheral and central neuropathy World Health Organization. Concise International Chemical Assessment Document 54; 2003. http://www.who.int/ipcs/publications/cicad/en/cicad54.pdf Hazardous Substances Database; National Library of Medicine. https://toxnet.nlm.nih.gov/cgi- bin/sis/search2/f?./temp/~7WUNLz:1 17

CDC/NIOSH Occupational Studies- EtO  Cancer Mortality Study 1  Cohort of 18,235 men and women in 14 U.S. commercial sterilization facilities; initially evaluated through 1987, with follow-up 1987-1998; average EtO exposure: 4.7 ppm (1975), decreasing to <1 ppm (1986)  Increased mortality from lymphoid cancers (Non-Hodgkin lymphoma, myeloma, and lymphocytic leukemia) for men in highest cumulative exposure group; Odds ratio = 3.76 (CI: 1.03-13.64)  Increased mortality from breast cancer in women for highest cumulative exposure group; Odds ratio = 3.13 (CI: 1.42-6.92) 1 Steenland, K. et al., Occup. Environ. Med. 61: 2-7, 2004. 18

CDC/NIOSH Occupational Studies-EtO  Breast Cancer Incidence 2 • 7,576 women, employed in commercial sterilization facilities for average of 10.7 years • Average EtO exposure: 4.7 ppm (1975), decreasing to <1 ppm (1986) • Odds Ratio = 1.87 (CI: 1.12-3.10) for highest cumulative exposure group . 2 Steenland, K. et al., Cancer Causes Control 14: 531-539, 2003 19

EtO Inhalation Unit Risk (IUR)  Inhalation unit risk (IUR) is an estimate of the increased cancer risk from inhalation exposure to a concentration of 1 µg/m 3 for a lifetime. The IUR can be multiplied by an estimate of lifetime exposure (in µg/m 3 ) to estimate the lifetime cancer risk.  The IUR (ug/m 3 ) -1 is the slope of the Dose-Response curve, and correlates with the potency for a chemical to cause cancer.  No threshold considered for a mutagenic chemical. https://www.epa.gov/iris/basic-information-about-integrated-risk-information-system 20 20