Ethylene Oxide Residues on Sterilized

Medical Devices

Stephen L. Brown and Joseph V. Rodricks

ENVIRON Corporation
Washington, DC

ABSTRACT

Ethylene oxide is used to sterilize a variety of medical devices, and patients who use
these devices may be exposed to residues of the ethylene oxide left on them. Ethylene
oxide is associated with cancer in laboratory animals and can cause a variety of other toxic
effects at sufficiently high doses, as can its reaction products, ethylene glycol and ethylene
chlorohydrin. Patient exposures to these chemicals can be estimated by considering the
numbers of devices sold in the U.S., the numbers of procedures performed that involve
devices, the duration and nature of contact with the patient, and other factors. This paper
describes a methodology for quantitative assessment of the risks from exposure to ethylene
oxide residues on medical devices.

KEYWORDS: Ethylene oxide, ethylene glycol, ethylene chlorohydrin, medical devices,

residues

INTRODUCTION

Ethylene oxide (EtO) is the sterilant of choice for many medical devices, some of
which cannot be effectively sterilized with radiation, steam, or any other alternative. Many
disposable and reusable medical devices, ranging from the common adhesive bandage to
pacemaker systems and dialyzers (see Table 1), are sterilized with EtO by the manufacturer
or custom sterilization companies prior to shipment for use.

After sterilization, some of the EtO may remain adsorbed on the surface of the device
or dissolved into its materials of construction. These residues dissipate with time at a rate
depending on the materials, the degree of aeration, and other factors. During sterilization,
some of the EtO may react with water vapor to form ethylene glycol (EG) or with
chlorinated compounds to form ethylene chlorohydrin (ECH), either of which may also
remain on the device.

Each of these three compounds has been shown to cause chronic toxicity or
reproductive effects in laboratory animals at relatively high doses. In addition, EtO has
tested positive in animal cancer bioassays and has been associated with human cancers in
epidemiological studies of uncertain significance. When the potencies of the three
compounds are compared among the various endpoints, it appears that protection against
EtO residues will generally protect against the other two compounds.

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© Plenum Press, New York 1989
 Table 1. Example Medical Devices That May Be
Sterilized with Ethylene Oxide

Bags, blood administration Pacemakers and accessories

Bags, IV administration Prostheses, breast
Bandages, adhesive Reservoirs, cardiotomy
Catheters, intravascular Sponges, gauze and cotton
Catheters, urological Syringes,hypodennic
Dialyzers and accessories Syringes, insulin
Filters, blood Tips, surgical suction
Gloves, surgical Tubes, infant feeding
Lenses, intraocular Tubing, blood or IV
Needles, hypodennic Valves, heart, prosthetic

Given these facts, it is reasonable to ask whether the residues of EtO on sterilized
medical devices pose unacceptable risks to patients using those devices. The Health
Industry Manufacturers Association contracted with ENVIRON Corporation to investigate
this question. The scope of our study included only risks to patients, not to medical
personnel or employees of manufacturers or sterilizing companies, and only the risks
associated with medical devices delivered sterile to hospitals, physicians, or the patient, not
the risks of devices that are sterilized or resterilized in the hospital or clinic.

TOXICITY ASSESSMENT

The carcinogenicity of EtO is described in terms of its potency or Unit Cancer Risk
(UCR), the slope of the dose-response relationship projected to hold at low doses. All of
the noncancer effects are described by the No Observed Effect Level (NOEL), the chronic
daily dose below which no effects of consequence have been seen in the most sensitive
species studied, or the Lowest Observed Effect Level (LOEL), also from the most sensitive
species, if no NOEL has been clearly identified.

Carcinogenicity

The cancer potency of EtO is based on studies in rats and mice that showed excesses
of leukemias, brain tumors, and other cancers after exposure to air concentrations of 100
ppm or somewhat lower (Snellings, 1984; Lynch et al., 1984; NTP, 1986). These data were
analyzed by the method of Gaylor and Kodell (1980), which produces an upper confidence
limit on the low-dose response to a carcinogen, assuming equal potency in humans and
animals on the basis of daily dose per unit body weight. The UCR of EtO predicted by this
method is 4.8 x 10-2 (mg/kg/day)-l.

Chronic and Reproductive Toxicity

EtO can cause neurologic and hematologic effects as well as damage to lungs, liver,
kidney, and testes (USEPA, 1985; Sprinz et al., 1982; Snellings et al., 1984a, 1984b).
Snellings et al. (1984b) showed that no effects were observed in rats exposed to 10 ppm for
6 hours per day, 5 days per week. The corresponding NOEL in humans is calculated to be
2 mg/kg/day. The reproductive NOEL for EtO is estimated to be 9 mg/kg/day, based
principally on a study by Snellings et al. (1982), in which no adverse reproductive
outcomes were seen in rats exposed to 33 ppm for 6 hours daily.

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