Journal of Hospital Infection (2005) 59, 361364

www.elsevierhealth.com/journals/jhin

SHORT REPORT

Residual formaldehyde on plastic materials and medical equipment following low-temperature steam and formaldehyde sterilization
K. Kanemitsua,*, H. Kunishimaa, T. Sagaa, H. Harigaea, T. Imasakab, Y. Hirayamab, M. Kakua
a

Department of Molecular Diagnostics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan b Department of Medical Systems, Central Uni Co. Ltd, Onojo, Fukuoka 816-0932, Japan
Received 1 October 2003; accepted 29 September 2004 Available online 29 January 2005

KEYWORDS
Residual formaldehyde; Lowtemperature steam and formaldehyde sterilization; European Standard EN14180; Medical materials

Summary We measured the amount of residual formaldehyde on 16 plastic materials and ve medical devices following low-temperature steam and formaldehyde (LTSF) sterilization, based on the European Standard EN14180. The amounts of formaldehyde residue on the plastic materials were compared with that on a lter paper of similar dimensions. The amount of residual formaldehyde on polyamide 6, polyurethane, natural rubber and polyacetal was higher (21.9, 15.2, 3.0 and 2.1 times, respectively) than that on the lter paper. The amount of formaldehyde recovered from a breathing circuit, anaesthesia circuit, oxygen tubing, airway tube and tweezers was 260, 240, 594, 56 and 0 mg, respectively, following LTSF sterilization. Our results emphasize the need to verify the main material composing the medical equipment before LTSF sterilization, as the amount of formaldehyde retrieved following sterilization varies according to the material used for construction. Q 2004 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

Introduction
Low-temperature steam and formaldehyde (LTSF)

* Corresponding author. Tel.: C81 22 717 7373; fax: C81 22 717 7390. E-mail address: kane2@mail.tains.tohoku.ac.jp

sterilization is widely used in European countries for sterilization of heat-labile medical equipment. Good sterilization methods should not only result in excellent sterilization, but should also be safe for humans and the environment. With regard to LTSF sterilization, there is sufcient evidence to indicate that the sterilization method is adequate for its use in clinical settings. However, there is little or

0195-6701/$ - see front matter Q 2004 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2004.09.039

362 no information on the level of residual formaldehyde following LTSF sterilization. If residual formaldehyde exceeds a certain level, it may be harmful to human tissue because formaldehyde is known to be toxic and carcinogenic. Previously, we have determined the level of residual formaldehyde on lter paper following LTSF sterilization based on the European Standard Draft prEN14180 published in May 2001,1 but there are no data available to quantify the amount of residual formaldehyde on medical equipment. Medical equipment can be made of various plastic materials. However, the inuence of the type of plastic material on the level of residual formaldehyde is not clear. This paper reports the residual formaldehyde levels of various plastic materials and actual medical devices following LTSF sterilization.

K. Kanemitsu et al. Co., Tokyo, Japan); and ABS resin (ABS-N-WN, ShinKobe Electric Machinery Co.). Polyacetal (Duraconsheet M25, Sheedom Co., Osaka, Japan), natural rubber (NR, Fuji-Pakkin Seisakusyo, Osaka, Japan) and butyl rubber (IB-300, Irumagawa Rubber Co.) were processed to the same diameter (70 mm) as the lter paper indicator (00R, Munktell AB, Sweden) designated in EN14180. Each piece of plastic was double-packed in the sterilization bag (HM304, Hogi Medical, Tokyo, Japan) and placed in the chamber. Immediately after sterilization, the plastic materials and the lter paper were placed in 25.6 mL of 0.2 M NaOH (1 mL per 3 cm2 of plastic material according to the Japanese guideline) and left for 72 h at room temperature. Ten millilitres of chromotropic reagent (disodium chromotropate dihydrate, Kanto Chemical, Tokyo, Japan) was mixed with 1 mL of this extraction within the test tube. The test tube was then placed in boiling water with constant shaking for 45 min, and a compound of formaldehyde and chromotropic reagent was generated. Results were measured at an excitation wavelength of 560 nm. The values of residual formaldehyde were calculated using the absorbance/formaldehyde concentration curve. Three independent experiments were performed.

Methods
We evaluated the residual formaldehyde levels according to the European Standard EN14180. The technique for extraction of formaldehyde was based on the Japanese guideline Sample/solvent and Extraction Conditions.2 This method is almost identical to the ISO/DIS 10993-12 Biological Evaluation of Medical Devices-Part 12: Sample Preparation and Reference Materials (1994).3 An LTSF sterilizer GEF 449 (Getinge AB, Getinge, Sweden) was used in this study. This sterilizer has a 185-L chamber, which is injected with 3438% formalin during operation. Formaldehyde solution was purchased from Wako Pure Chemical Industries (Osaka, Japan). The sterilization temperature was set at 55 8C.

Examination of medical equipment

A breathing circuit (F-Type, Mera Senko-Ika Co., Tokyo, Japan), anaesthesia circuit (8600B-06, King System Co., India, USA), oxygen tubing (2002, Salter Labs Co., California, USA), airway tube (100/303 Portex, Smiths Medical Co., London, UK) and tweezers (STA-1, AS ONE Co., Osaka, Japan) were double-packed in the sterilization bag and placed in the chamber. Immediately after sterilization, each was immersed completely in 0.2 M NaOH and left for 72 h at room temperature. Subsequent examination procedures were similar to those described above.

Examination of various plastic materials

The following plastic materials were examined: soft polyvinyl chloride (8125, Est-Nikko Co., Osaka, Japan); low-density polyethylene (EH-N-AN, ShinKobe Electric Machinery Co., Tokyo, Japan); polypropylene (PP-N-AN, Shin-Kobe Electric Machinery Co.); polycarbonate (NF-2000, Mitsubishi Engineering-Plastics Co., Tokyo, Japan); polyurethane (SL1090, Somar-Gomu Co., Saitama, Japan); polystyrene (AE2010, Eiken Kizai Co., Tokyo, Japan); silicon (IB-825, Irumagawa Rubber Co., Tokyo, Japan); polymethylmethacrylate (KLALEX-S, NittoJyushi Co., Tokyo, Japan); polytetrauoroethylene (#9000, Nichias Co., Tokyo, Japan); polyethylene terephthalate (Lumirror, Toray Co., Tokyo, Japan); polyamide 6 (MC143, Kanebo Co., Tokyo, Japan); polysulphone (P-1700, Amoco Engineering Polymer

Results
The amount of residual formaldehyde on 12 of the 16 types of plastic was less than that on the lter paper, while it was higher on the other four types of plastic (Table I). Compared with the lter paper, the amount of residual formaldehyde on polyamide 6, polyurethane, natural rubber and polyacetal was 21.9, 15.2, 3.0 and 2.1 times greater than that on the lter paper, respectively. Residual formaldehyde was retrieved from four medical devices, but not from the tweezers. As

Residual formaldehyde following LTSF sterilization

Table I Amount of formaldehyde residue on plastic materials and lter paper Material Thickness (mm) First 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
a

363

Formaldehyde residue (mg) Second 14.2 0.5 14.2 27.8 865.1 14.2 65.1 4.2 K2.2 4.2 930.5 43.3 14.2 119.6 199.6 46.9 53.3 Third 14.2 2.4 2.4 26.9 861.5 17.8 70.5 4.2 1.5 6.0 1220.5 30.5 37.8 122.4 104.2 37.8 61.5 Average 14.8 1.5 7.2 26.6 866.0 15.7 74.5 4.8 K0.7 6.3 1243.6 47.5 25.7 119.6 172.1 43.9 56.9

Ratioa

Soft polyvinyl chloride Low-density polyethylene Polypropylene Polycarbonate Polyurethane Polystyrene Silicon Polymethylmethacrylate Polytetrauoroethylene Polyethylene terephthalate Polyamide 6 Polysulphone ABS resin Polyacetal Natural rubber Butyl rubber Filter paper

0.5 0.5 0.5 0.5 1 1 0.5 0.5 0.5 0.5 0.5 1 1 0.5 0.5 1 0.22

16.0 1.5 5.1 25.1 871.5 15.1 87.8 6.0 K1.3 8.7 1579.6 68.7 25.1 116.9 212.4 46.9 56.0

0.3 0.0 0.1 0.5 15.2 0.3 1.3 0.1 0.0 0.1 21.9 0.8 0.5 2.1 3.0 0.8 1.0

Ratio: amount of formaldehyde in the sample relative to that on the lter paper.

shown in Table II, the largest amount of residual formaldehyde was detected on the oxygen tubing.

Discussion
The usefulness of LTSF sterilization is recognized widely in Europe4,5 as a method of low-temperature sterilization. LTSF sterilization is thought to sterilize various types of heat-labile medical equipment effectively. Many sophisticated pieces of medical equipment, such as exible endoscopes, are complex, re-usable instruments that need to be sterilized before they are re-used. Furthermore, medical equipment may have many parts that are made of various materials. Thus, it is necessary to know how much formaldehyde residue remains on these devices following LTSF sterilization. At present, there is little or no information regarding
Table II Equipment Breathing circuit Anaesthesia circuit Oxygen tubing Airway tube Tweezers
a

residual formaldehyde levels on various materials and specic items of medical equipment. Our results showed that residual formaldehyde levels were lower on 12 plastic materials, but higher on four other plastic materials, compared with the lter paper. Notably, the residual formaldehyde levels on polyurethane and polyamide 6 were 15 times higher than that on the lter paper. The permeability of materials, the afnity with formaldehyde and the properties of the surface could all inuence the amount of residual formaldehyde. However, our study did not investigate these issues. Meanwhile, Vagn Handlos68 reported that the level of residual formaldehyde on polyamide 6 was less than that on the lter paper. These contradictory data are probably due to the different methods used for measurement of formaldehyde. We also measured the amount of residual formaldehyde on ve medical devices following sterilization. Residual formaldehyde was detected

Amount of formaldehyde residue on medical equipment Main material Ethylene vinyl acetate copolymer Ethylene vinyl acetate copolymer Soft polyvinyl chloride Soft polyvinyl chloride Stainless steel Weight (g) 176 196 54 20 22 NaOH (mL)a 2500 4800 400 540 18.5 Formaldehyde residue (mg) 260 240 594 56 0

0.2 M NaOH used as formaldehyde extraction solvent.

364 on four pieces of equipment, but not on the tweezers. These four types of equipment are, in principle, disposable products; however, they are often re-used following sterilization in hospitals. When LTSF is used for sterilization, it is necessary to conrm that formaldehyde residues remain below certain levels, in addition to complete sterilization and without affecting the functional integrity of the equipment. At present, there are no standardized safety criteria regarding the level of formaldehyde residues on sterilized medical equipment. According to the Dutch RIVM report 71041018 issued in 1992, the safety limit of intravenous exposure (and inhalation) to formaldehyde residues was calculated at 16.8 mg. This value is based on the LD50 values calculated in several animal species and exposure routes. Such calculation takes into account a safety margin of 250 to translate from animal data to one-time exposure in humans. On the other hand, the mean safety limit value was set at 200 mg in EN14180, which is approximately 80 times lower than the limit for intravenous exposure. It is noteworthy that the amount of formaldehyde residue in the oxygen tubing exceeded 200 mg in our study. Both the oxygen tubing and airway tube used in this study were made of soft polyvinyl chloride. The residual formaldehyde on the soft polyvinyl chloride was low compared with the lter paper (ratio: 0.3); however, the amounts of residual formaldehyde on the oxygen tubing and airway tube were 594 mg and 56 mg, respectively. The high levels of residual formaldehyde on these two medical devices may be due to the large surface area. The breathing and anaesthesia circuits used in our study were made of ethylene vinyl acetate copolymer, and this material was not tested in our study. The amount of retrieved formaldehyde correlated with the sterilization temperature. Previously, we reported that the mean value of residual formaldehyde on lter paper was 181 mg

K. Kanemitsu et al. at a sterilization temperature of 50 8C, but this decreased to 32 mg at 80 8C.9 Therefore, at a sterilization temperature of 80 8C, it may be possible to decrease the level of residual formaldehyde after LTSF sterilization. Alternatively, the amount of residual formaldehyde can be reduced by increasing the number of vacuum and steam pulses or air pulses. In conclusion, the material composing the medical equipment should be veried when LTSF sterilization is performed, because the amount of formaldehyde residue varies according to the surface area and the material used for construction.

References
1. Technical Committee CEN/TC 102. Sterilizers for medical purposeslow temperature steam and formaldehyde sterilizersrequirements and testing. British Standard Institution, London, UK. EN 14180 2001. 2. Ministry of Health, Labour and Welfare of Japan. Pharmaceutical and Food Safety Bureau. Guidelines for basic biological tests of medical materials and devices. Tokyo, Japan: Ministry of Health, Labour and Welfare of Japan. 1996. p. 187. 3. International Organization for Standardization. Biological evaluation of medical device Part 12: Sample preparation and reference materials. ISO 10993-12. 2002. 4. Babb J, Ayliffe G, Bradley C. Decontamination of minimally invasive surgical endoscopes and accessories. J Hosp Infect 2000;45:263277. 5. Rutala WA, Weber DJ. New disinfection and sterilization methods. Emerg Infect Dis 2001;7:348353. 6. Handlos V. Formaldehyde sterilization-1. Determination of formaldehyde residuals in autoclave sterilized materials. Arch Pharm Chem 1977;5:163169. 7. Handlos V. Formaldehyde sterilization-2. Formaldehydesteam sterilization, the process and its inuence on the formaldehyde residuals. Arch Pharm Chem 1979;7:12. 8. Handlos V. Formaldehyde sterilization-3. The behaviour of the loaded autoclave and the permeability of plastic materials to formaldehyde. Arch Pharm Chem 1979;7:1218. 9. Kanemitsu K, Kunishima H, Kaky M, et al. Evaluation of low temperature steam and formaldehyde sterilizer. J Hosp Infect 2003;55:4752.