1、API TR*407 95 0732270 0552302 bT2 American Petroleum Institute Health and Environmental Sciences Department Primary Skin Irritation Study in Rabbits of: API 91-01 and PS-6 Un leaded Test Gasolines MARCH 1995 TOXICOLOGY REPORT NUMBER 409 CAIS ABSTRACT NO. 42-2014 One of the most significant long-term
2、 trends affecting the future vitality of the petroleum industry is the publics concerns about the environment. Recognizing this trend, API member companies have developed a positive, forward-looking strategy called STEP: Strategies for Todays Environmental Partnership. This program aims to address p
3、ublic concerns by improving our industrys environmental, health and safety performance; documenting performance improvements; and communicating them to the public. The foundation of STEP is the API Environmental Mission and Guiding Environmental Principles. API ENVIRONMENTAL MISSION AND GUIDING ENVI
4、RONMENTAL PRINCIPLES The members of the American Petroleum Institute are dedicated to continuous efforts to improve the compatibility of our operations with the environment while economically developing energy resources and supplying high quality products and services to consumers. The members recog
5、nize the importance of efficiently meeting societys needs and our responsibility to work with the public, the government, and others to develop and to use natural resources in an environmentally sound manner while protecting the health and safety of our employees and the public. To meet these respon
6、sibilities, API members pledge to manage our businesses according to these principles: 4 To recognize and to respond to communi concerns about our raw materials, products and operations. 9 To operate our plants and facilities, and to handle our raw materials and products in a manner that protects th
7、e environment, and the safety and health of our employees and the public. 9 To make safety, health and environmental considerations a priori in our planning, and our development of new products and processes. 9 To advise promptly, appropriate officials, employees, customers and the public of informa
8、tion on significant industry-related safety, health and environmental hazards, and to recommend protective measures. 4 To counsel customers, transporters and others in the safe use, transportation and disposal of our raw materials, products and waste materials. O To economically develop and produce
9、natural resources and to conserve those resources by using energy efficiently. 4 To extend knowledge by conducting or supporting research on the safety, health and environmental effects of our raw materials, products, processes and waste materials. O To commit to reduce overall emission and waste ge
10、neration. e:. To work with others to resolve problems created by handling and disposal of hazardous substances from our operations. 8. To participate with government and others in creating responsible laws, regulations and standards to safeguard the community, workplace and environment. 9 To promote
11、 these principles and practices by sharing experiences and offering assistance to others who produce, handle, use, transport or dispose of similar raw materials, petroleum products and wastes. API TR*409 95 m 0732290 0552304 475 m Revised Final Report I Primary Skin Irritation Study in Rabbits of: A
12、PI 91-01 and PS-6 for: American Petroleum Institute Hill Top Biolabs Project No. 93-8177-21 (A) HILL Top BIOCABS, INC. PO. Box 429501 Cincinnati, Ohio 45242 - 513/831-3114 - fax 513/831-1217 Tk Hi117op Comparms HuI %p FksaKh, Inc. HI1 lp phamiat 9-2-45 Study Director Acute Toxicology Project Monitor
13、: HILL TOP BIOLABS, INC. Kennethd. Harrod, B.A. Research Associate II Acute Toxicology Report Issued by: HILL TOP BIOLABS, INC. Edwin V. Buehler, Ph.D. 3 .a -95 4% Vice President, Scientific Affairs Acute Toxicology Page 6 of 47 API TR*409 95 0732290 0552115 250 m American Petroleum Institute Ref.:
14、93-8177-21 (A) CONTRIBUTORS Revised Final Report I February 1, 1995 The following members of Hill Top Biolabs, Inc., contributed to the conduct and reporting of Project No. 93-8177-21 (A): Name Function E. Buehler, Ph.D. Vice President, Scientific Affairs Manager, Director of Toxicology Toxicology J
15、. Kreuzmann, B.A. Group Director and General Manager, Manager Toxicology T. Morris, B.S. Operations Manager Study Director Conduct of Study M. Watson Research Supervisor Conduct of Study K. Harrod, B.A. Research Associate II B. Lynn, AS. Project Coordinator Technician Project Monitor Conduct of Stud
16、y Conduct of Study D. Bergman, B.S. Technician Conduct of Study C. Sloan Animal Husbandry Technician I Conduct of Study D. Lewis Report Coordinator Report Preparation Page 7 of 47 API TRr409 95 0732290 0552LLb 197 American Petroleum Institute Revised Final Report I Ref.: 93-8177-21 (A) Project No.:
17、Test/Protocol No.: Testing Facility: Sponsor: Sample Identification: Source of Animals: Date Study Initiated: Date Project Started: Date Project Completed: February 1, 1995 GENERAL INFORMATION 93-8177-21 (A) Primary Skin Irritation Study in Rabbits Hill Top Biolabs, Inc. Main and Mill Streets Miamiv
18、ille, OH 45147 American Petroleum Institute 1220 L Street, Northwest Washington, D.C. 20005 API 91-01 and PS-6 Myrtles Rabbitry Incorporated 4678 Bethesda Road Thompson Station, Tennessee 371 79 January 7, 1994 January 11 , 1994 January 25, 1994 2-4-2/03-09-90/REV 3 SAMPLE CHARACTERIZATION AND STABI
19、LITY The Sponsor has assumed responsibility for test substance derivation, characterization, and stability testing. The test material, API 91-01 unleaded gasoline (EPL #470), 40 ML Sample, Sampled 1 1 /9/93, was received from Experimental Pathology Laboratories, Inc., on November 11, 1993, for use i
20、n this study. The test material was a clear pink liquid and was stored at room temperature in a brown glass jar with a brown plastic screw top. The test material was disposed of following the completion of testing. The test material, PS-6 unleaded gasoline, was received from CIIT at the direction of
21、 the American Petroleum Institute on December 14, 1993, for use in this study. The test material was a clear yellow liquid and was stored at room temperature through- out the study in a metal canister with a blue plastic lid. The test material was disposed of following the completion of testing. DAT
22、A RETENTION The raw data and the original final report will be sent to the Sponsor within six months following completion of the study. The testing facility will retain a copy of these study records in the form of microfilm. Page 8 of 47 API TR*409 95 = 0732290 0552117 023 = American Petroleum Insti
23、tute Ref.: 93-8177-21 (A) SUMMARYICONCLUSIONS Revised Final Report I February 1, 1995 This study was designed to assess the potential of API 91-01 and PS-6 to cause irritation after a single topical application to the intact skin of New Zealand White Rabbits under occluded and semi-occluded conditio
24、ns. The primary skin irritancy of undiluted API 91-01 and PS-6, occluded and semi-occluded, was separately evaluated in compliance with the conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act (40 CFR), the Toxic Substances Control Act
25、 (40 CFR), and the OECD Guidelines. The Primary Irritation Index (Pli) and classification criteria for the two occlusion methods for the two different test materials are presented in the following table: Occlusion Matehl Mathod Occluded API 91-01 Semi-Occluded 1 Occluded PS-6 Semi-Occluded Rimry 1 i
26、rritation Index IPiI 4.8 4.3 4.8 3.7 very slight I Moderate I des;tion I Irritant well-defined desquamation Moderate on site and Irritent coriaceousness moderate very slight et edges of site Irritant I on site I moderate I very slight Moderate desquamation desquamation on site end moderate very slig
27、ht Initation Persisting 14 Dey. foliowhg appcetion very slight none none none Drake gt-. Primary Irritation Index (Pli) shown in the table above is based on the scores collected at the 24 and 72 hour readings. Clinical observations of each animal noted at the time of scoring indicated normal appeara
28、nce and behavior throughout the study. No evidence of corrosion (necrosis) was found. Page 9 of 47 API TR*:409 95 W 0732290 0552118 TbT W American Petroleum Institute Revised Final Report I Ref.: 93-8177-21 (A) February 1, 1995 METHODS (See Appendix 1 for Protocol and Supplemental Instructions) This
29、 standardized procedure was conducted according to the general conditions of the Protocol and specifically as designated in the Project Instruction Sheet and Supplemental Instructions, as applicable. As such, it satisfies the criteria established by the Federal Insecticide, Fungicide, and Rodenticid
30、e Act (40 CFR), the Toxic Substances Control Act (40 CFR), and the OECD Guidelines. A total of four groups of six young adult, New Zealand White rabbits (three males and three females per group) were used in this study. The groups were divided into two groups per test material, each test material ha
31、ving an occluded group and a sem -occluded group. Each animal in each occluded group received a 0.5 ml quantity of the appropriate undiluted test material onto a 1“ x 1“ gauze square. The patches were then held in place with adhesive tape. The test material was applied in this manner to one intact s
32、kin site per animal. After application of the patch, the trunk of each rabbit was wrapped with rubber dental dam which was secured with staples. An outer layer of gauze was then wrapped around the trunk of each animal and secured with tape. Each animal was fitted with an Elizabethan collar to preven
33、t wrapping and patch removal. Following approximately 4 hours of exposure, the restraining device, wrapping, and patches were removed. The test sites were wiped free of residual test material by a gentle sponging using a paper towel moistened with tap water. The semi-occluded method incorporated two
34、 Webril pads, which were removed from the adhesive, and placed on top of each other. Each animal in each semi-occluded group received a 0.5 ml quantity of the appropriate undiluted test material applied to the pads. The pads were then held in place with adhesive tape. The test material was applied i
35、n this manner to one intact skin site per animal. After application of the pads each animal was fitted with an Elizabethan collar to prevent wrapping and patch removal. Following approximately 4 hours of exposure, the restraining device and pads were removed. The test sites were wiped free of residu
36、al test material by a gentle sponging using a paper towel moistened with tap water. Page 10 of 47 - API TR*409 95 m 0732290 0552119 Tb m American Petroleum Institute Revised Final Report I Ref.: 93-8177-21 (A) February 1, 1995 For each group, the values for each rabbit were totaled and averaged for
37、each of the following categories: 1. Erythema and eschar formation, intact skin, 24 hours 2. Erythema and eschar formation, intact skin, 72 hours 3. Edema, intact skin, 24 hours 4. Edema, intact skin, 72 hours For each group, the four average scores from above were added together and the results div
38、ided by two to obtain the Primary Irritation Index (Pli). In accordance with the definition from 16 CFR 1500, a corrosive test material is one which causes destruction or irreversible damage to tissue within twenty-four hours or less, while a primary irritant is one which gives a PI1 of 5 or more on
39、 a scale of 0-8. The Draize summarizations are as follows: Non-irritant (0.1 - 2.0), Moderate Irritant (2.1 - 5.9), and Severe Irritant (6.0 and higher). Page 11 of 47 - API TR*409 95 0732290 O552320 bLB American Petroleum Institute Revised Final Report i Ref.: 93-8177-21 (A) February 1, 1995 RESULT
40、S The report as constituted presents all the important observations that are critical to the interpretation of the test. The results of the 4 hour occluded application of undiluted API 91-01 and PS-6 to intact skin areas are summarized in Tables 1 and 3. The results of the 4 hour semi-occluded appli
41、cation of undiluted API 91-01 and PS-6 to intact skin areas are summarized in Tables 2 and 4. Raw data may be found in Appendix 2. PROTOCOL DEVIATION The following deviation from the protocol occurred during the study: 1. Clinical observations for all animals participating on this Primary Skin Irrit
42、ation Study were erroneously not documented at the time of scoring on Days 7 and 14. However, general health observations are made on a daily basis for all animals. The animals participating on the study were in good health on the days that scoring took place. This deviation did not compromise any a
43、spect of this study. REFERENCE Draize, J.H. (1959). ADDraisai of the Safetv of Chemicals in Foods. Druas and Cosmetics. Association of Food and Drug Officials of the United States. Austin, Texas. Page 12 of 47 - API TR*409 95 0732290 0552323 554 American Petroleum Institute Ref.: 93-8177-21 (A) Tabl
44、e 1 Revised Final Report I February 1, 1995 Primary Skin Irritation in Rabbits Following a 4 Hour Dermal Application of API 91-01 Occluded Condition Score Erythema Formation SiteII A I BI BI 3 2H 3 3 2 2 2H 3 3 2 3 2 2H 2 2 2 2 2.00 12 1HZ 12 OZ OZ OZH 0.50 Day 14 1 O O O oz o 0.1 7 Intact II Edema
45、Formation II II Primary Irritation Index (PII) = 4.8* II Scoring key appended to report. bAt the time of removal, the test material appeared to have partially dissolved the adhesive tape, holding H = Hair on site. 2 = Desquamation on site. = PI1 is based on the scores collected at the 24 and 72 hour
46、 reading only. Site Key the patch in place which caused partial stripping of the skin surface when the patch was removed. Tail Page 13 of 47 - API TRx409 95 = 0732290 0552322 490 Score for each RabbiPb Skin Condition Reading NO. 22 I NO. 23 I NO. 24 I NO. 49 I NO. 50 I NO. 51 American Petroleum Inst
47、itute Ref.: 93-8177-21 (A) score Revised Final Report I February 1, 1995 Table 2 Primary Skin Irritation in Rabbits Following a 4 Hour Dermal Application of API 91-01 Semi-Occluded intact 2.00 2.33 2.67 2.67 0.83 0.00 II Edema Formation II I A D D B B II 1/2 - 1 hr ir Day 14 Intact Primary Irritatio
48、n Index (Pli) = 4.3* - ascoring key appended to report. H = Hair on site. E = One edge of site appeared coriaceus. R = Edges of site appeared coriaceus. Z = Desquamation on site. L = Animal clipped prior to scoring on Day 14 to aid in scoring. = PI1 is based on the scores collected at the 24 and 72
49、hour reading only. bSite Key 3 Tail Page 14 of 47 - API TR*409 95 I 0732290 0552323 327 American Petroleum Institute Ref.: 93-8177-21 (A) Table 3 Revised Final Report I February 1, 1995 Primary Skin Irritation in Rabbits Following a 4 Hour Dermal Application of PS-6 Occluded Score for each Rabbitabc Skin Erythema Formation I II siteII A I c I D I D I B I c II -11 Scoring key appended to report. bAt the time of removal, the test material appeared to have reacted with the adhesive tape, holding the H = Hair on
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