Minntech Corporation — Hazardous Materials Safety Interpretation

Page 1• • U.S.Department of Transportation Washington, D.C. 400 Seventh Street, S.W. 20590 Research and Administration Special Programs OCT / 1998 Mr. Richard M. Ormsbee Minntech Corporation Ref. No. 98-0232 14605 28th Avenue North Minneapolis, MN 55447 Dear Mr. Ormsbee: This is in response to your letter of August 12, 1998, on the determination of whether a material meets the definition for a Class 8 (corrosive) material under the Hazardous Materials Regulations (HMR; 49 CFR parts 171-180). Specifically you ask whether you may use the OECD guidelines (which require evaluation for 72 hours) to determine if a material is corrosive or if evaluation for 14 days is required to determine corrosivity for Packing Group II and III materials as provided by § 173.137. Your questions are paraphrased and answered as follows: l. Should the OECD guidelines be followed with the observation time extended to 14 days regardless of whether the material has shown full reversibility within a timespan of less than 14 days? A. The OECD guidelines were adopted in the HMR to provide the method to determine whether a material meets the criteria for a Class 8 hazardous material. For purposes of classification under the HMR evaluation of up to 14 days is required for Class 8 materials in Packing Groups II and III as provided by S 173.137. However, if a material causes full thickness destruction of intact tissue in less than 14 days no further observation is necessary.#

Page 2• • l. When classifying a material as corrosive or non-corrosive 72 hours? is the OECD method acceptable with an endpoint observation of A. The answer is no. For classification purposes of the HMR observation of up to 14 days is required. I hope this satisfies your request. Sincerely, Thomas I. Allan Thomas G. Allan Senior Transportation Specialist Office of Hazardous Materials Standards#

Page 3*--AUG-12-98 WED 10:11 AM MINNTECH FAX NO. 6125533387 P. 01/01 ."= Lavalle MINNTECH $173.135 Minntech Corporation 14605 28th Avenue North Minneapolis, MN 55447 U.S.A, 98-0232 FAX COVER SHEET DATE: TO: August 12, 1998 Edward T. Mazzullo TIME: FAX: 9:52 AM 202-366-3012 : FROM: Richard M. Ormsbee PHONE: 612 551-2689 FAX: 612-553-3387 RE: Observation times required for corrosivity testing CC: Number of pages including cover sheet: 1 Message Mr. Mazzullo, I would like to thank your office for the help that several people have provided me over the last couple of weeks. They have been very helpful in helping me understand several issues. I am writing you today to confirm that | properly understood the information that has been conveyed to me. Once a material has been classified as a corrosive, a packing group must be determined using 49 CFR 173.137. In order to classify a material as Packing Group Ill, one must follow the 1992 OECD Number 404 protocol but extend the observation period beyond 72 hours as called out in the OECD protocol. The OECD Number 404 states "Further observations may be needed to establish reversibility" ", and the 49 CFR 173.137(c)(1) states "That cause full thickness destruction of intact skin within an observation period of up to 14 days..... Am I correct to understand that the DOT wishes the OECD protocol to be followed, extending the observation times to 14 days regardless of whether a certain material has shown full reversibility within a timespan of less than 14 days? My next question has to do with (1997) 49 CFR 173.136 Class 8 - Definitions. When classifying a material as corrosive or non-corrosive, the 1992 OECD Guideline for Testing of Chemicals, Number 404 is acceptable with an endpoint observation time of 72 hours? Thank you for taking the time to answer and clarify these issues. Sincerely, /Richard M. Ormsbee • ... •...#

Page 43Eu-14-90 1.2/14/83 10:30 FROM: SWIDLER % BERL1I PAGE Adopied: 17.07.92 DECD GUIDELINE FOR TESTING OF CHEMICALS Adopted by the Council on 17° July 1992 • Acure Permal Irritation/Corrosion INTROPUCTION rogress. In the revlew, special amention is given to possible improvements in reladon to anim • OECD Guidelines for Testing of Chemicals are periodically revlewed in lighs of scienun • meeting of OECD expens held in Paris in May 1991. welfare. This updated version of the original guideline 404 (adopied in 1981) is the outcome of a 2. inclusion of data from in vito tests in the information on which a decision not to pracced to an in vivo The main differences between this and the original version of the guideline are: 1) the rest can be based; and b) the possibility to use one animal in a firsi step of the in vivo procedure allowing corain chemicals to be exempled fium furior lesling. 3. Definidions used are set our in the Annex. INITIAL CONSIDERATIONS avoided, and that any testing which is likely to produce severe responses in animals is minimised In the interests of animal welfare, il is important thas the unnecessary use of animals is dermal irritation/corrosion: Consequently, lest materials meeting any of the following criteria should nos be lested in anlmals for 1) materials that have predictable corrosive potental. based on structure-sctivity e.g.. when the material to be applied has a pri of 2 or less or 11.5 or greater (alkaline relationships and/or physicochemicai properties such as sirong acidity or alkalinisy, - Or acidie reserve (1) should also be teken into account): materials which have been shown to be highly roxic by the dermal rouce: 11I) materials which, in an acure dermal toxicity test (2), have been shown not to produce irritation of the skin at the limit zest dose level of 2000 maky body weight predicted on the basis of results from in vitro rests (3). In addition, It may not be necessary lo test la vivo materials for which corrosive properties are - • -. PRINCIPLE OF THE IN VIVO TEST animes, untreaied skin areas of ine lest animals) serving 2s control. The desree of imitation is read The substance to be lested is appled in a single dose to the skin of one or more experiment : 1/6 -#

Page 512454 Dali In UNDU - ULDSTOLCI ... and scored at specified intervals and is further described in order to provide a complete evaluation of the effects. The duradon of the study should be sufficlent to evaluate fully the reversibility of the effects observed.. Animals showing severe distress andor pain al any siage of the rest must be humanely killed. DESCRIPTION OF THE IN VIVO METHOD Selection eL animal species 6. Several mammalian species may be used. The altino rabbit ls the preferred species. Number and sex of animal can be used. Additional animals may be used to clarity equivocal resporses. Somelimes the zest can Three healthy adult animais are required for the complete test Male endor female enimals be performed with are animal only. Housine and feedine sonditions should be 20°C (+ 3°C) for rabblis, 22°C (+ 3°C) for rodents and the relauve humidity 30 10 70 per Animals should be individually housed. The temperature of the experimental animel room" cent. Where the lighting is ardificial, the sequence should be 12 hours leh, 12 hours dark Conventional laboraiory diers are sultable for feeding and an unrerricied supply of drinking wates showd be available. Preparation of the enimals 9. area of the trunk of the animals. Cart should be taken to avoid abrading the skin and only animals Approximarely 24 hours before the test, fur should be removed by close-clipping the dorsal with healthy intact skin should be used. 10. Some strains of rabbit have dense parches of hair which are more prominens al certain times of the year. Such areas of dense hair growth should not be used as patch sites. PROCEDURE • Applisation of the test substance The test substance should be applled to a small area (approximately 6 cm?) of skin and coyerod with a gauze patch, which is heid in place with non-imating tape. In the case of liquids or some pastes, it may be necessary so apply the test subslance to the gauze patch and then apply that to the skin. The parch should be loozely held in contacs with the skin by means of a suitable semi-occlusive dressing fos the durazion of the exposure period. Access by the animal io the parch and resultant ingestion/inhalation of the rest subscence should be prevensed 12. Liquid test substances are generally used undiluled. When testing solids (which may be pulverised if considered necessary), the less subsiänce should be moistened with the smallest amount of waser, or where necessary & fuitable vehicle, needed to ensure good contact with the skin. When venicles are used, the influence of the vehicle on Immation of the skin by the test substance should be taken into account. 13. At the end of the exposure period, normally & hours, residual sess substance should be 2/6 -#

Page 612/14/8315:22 removed, where practicable, wing waler or an appropriale solvent without ellering the exiting response or the integrity of the epidermis. Dose level 14. A dose of 0.5 mi of liquid or 0.5 g of solid or semi-solld is applied to the test site. Expertie of one animal 15. Il it is suspected that the sest substance mizhi produce severe irritancy/corrosion, & single rest parches are applied simulianeously so the animal. Ine first parch is removed after three minutes. animal rest should be employed. When it is suspected that the substance may cause corrosion, three If no serious skin resction is observed, the second patch in removed after one hour. If the observatons Is removed after four hours and the responses are graded. I! & corrosive effect is observed after elther al Lais slage indicate that exposure ear humanely Do allowed to exend to four hows, the third parch three minutes or one hour exposure, the lest is immediaiely terminated by removal of the remaining patches. Altematively, the three patches may be applied sequendaily. When it is suspecied whar the substance may cause severe imitancy, & single paich should be applied to the animal for four hours. •. Exposure ele further twe animals 16. If neither a corrosive effect nor a severe imiant effect is observed after a four hour exposure, period of four hours. the test should be complered wins two addional animals, cach with one parch only, for ar exposure Expósure of shree animals 17. may be site expected animals, due rect in one pace for an exposure or or our hone Qbservation period 18. The duraton of the obseryation perted thould not be fixed rigidly bur should be sumcient is evaluate fully the reversibility of the effocts observed. Sunleal observations and stadine of skin reastions 19. Animals should be examined for signs of erythema and oedema and the responses scored ai recorded and fully described. 3/6#

Page 712/14/83.15:22 TABLE: GRARING OF SKIN REACTION Erythema and Eschar Fermation No erythema Well defined erytema Very slight erytherna (barely percepuble) Moderate lo severe erythema 2 Sovere erythema (occi redness) to eschar formaton 3 prevenuing grading of erythama. 4 Meximum possible: 4 Sedema Formatien :.. No oedema Very slight oedema (oarely percepuble) ..• 0 Moderate oedema (raised approximately 1 mllimetre) Slight ocdera (edges of trea well defined by definite raising) ..• 2 Severe oedema (raised more than 1 millimert 3 and extending beyond area of exposure) .... ... Maximum possible: 4 Histopathologicel examination may be carried our to clarily doubtful reactions. DATA AND REPORTING Pass 20. Data should be summarised in lbular form, showing for cach individual animal the irritation scores for erythema and ocdera al 60 minutes, 24,48 and 72 hours after paich removal, all lesions. a description of the dogree and nature of irrilation, corrosion or reversibllity, and any orber toxic effects observed. Intreport 21. The rest repor must include the following infomation: Tess substance: identification dace physical nature and, where relevant, physicochemical properties: Vehicle: • jusufication for choice of vehicle. Tess animais: • : species, al and der • number, age and sex of animals: 4/6 -#

Page 812/14i zaui iso yuou ...• ?.- • . spare a use gond is diat he star and at the concludio of the lost. Test conditions: - : technique of patch sise proparation; details of parch materials used and parching rechnique: • decalls of last rubslence preparation, application and removal. Resules: - tabulation of inication response data for cach individual animal for each reMOYal); observation time perlod (c.8. 60 minures, 24, 48 and 72 hours after parch • description of all lesions observed; sarrive descripzion of the degree and nature of imriation observed, and any histopachological findings; description of any other toxic effects in addition to dermal Iration/corrosion. • Discussion of the results. including details of the procedure, must be given together with results oblained with the tess and Il an in vitro sest is performed before the in vivo rest, the description or referencs of the resh reference substances. LITERATURE (1) Young J.R., How M.J., Walker A.P. and Wonh W.M.H. (1988). Classification as corrosive or irritant to skin of preparations cantalning acidic or alkaline substances withour testing on animals. Toxicology in Viro, 2. 19-26. (2) OECD, Parts (1987). Guideline 402. (3) : ECETOC Monograph No. 15, "Skin Imation", European Chemical Industry, Ecology and Toxicology Centre, Brussels, July, 1990. 5/6#

Page 9DEC - 14-93 14-1431: 32. FROM: USE BERLIN E0zMYD: 2024247643 ....PAGE - ANNEX DEFINITIONS Dermal irication is the producion of reversible infammatory changes in the skin following the applicadon of a les: subrance. D me corgin l the produston of inevertlic listue danage In the skia following the application. .:.-. 6/6#