Document 3eMx91E0rjkko6OG6qRzOoVKy

!)w&uAtilal BIO - T E s T JlalsGKit&ujeA,, 3m. 1810 frontage road NORTHBROOK, ILLINOIS 60062 February 9, 1977 Dr. Zeb G. Bell, Jr., Manager Environmental Health and Toxicology Chemical Division PPG Industries, Inc. One Gateway Center Pittsburgh, Pennsylvania 15222 Dear Dr. Bell: Re: IBT No. 8562*09334 * Dominant Lethal Study with Trichloroethylene in Albino Rats - Exposed Via Inhalation We are submitting herewith our laboratory report prepared in connection with the above study. Very truly yours. JCC: jd J. C. Calandra President SL 032226 Dndud&u&l B I O - T E S T J.aluMattvu&&, D*tc. REPORT TO PPG INDUSTRIES, INC. DOMINANT LETHAL STUDY WITH TRICHLOROETHYLENE IN ALBINO RATS EXPOSED VIA INHALATION FEBRUARY 9, 1977 IBT NO. 8562-09334 I. Introduction A mutation is a change in the character of a gene such that morphologic, physiologic and/or biochemical alterations are produced. If this change in . gene character occurs in the germinal cell, the alteration can be transmitted to succeeding generations. Changes of this nature can be artificially induced (irradiation, chemical exposure) or they may be spontaneous. A dominant lethal mutation occurring in a male germinal cell may lead upon fertilization by the affected cell, to the failure of development of the resulting zygote beyond the blastocyst stage (implantation). Male rats, treated with the test compound, are mated with untreated females. The numbers of pre-implantation losses and early resorptions in female rats, dissected at mid-gestation, are used to calcu late the mutation rate based on the induction of dominant lethal mutations. SL 032227 yadH&inial B I O - T E S T JlaM&iat&Uei, Hhc. 2 II. Summary A dominant lethal mutagenic study was conducted on albino rats treated via inhalation with Trichloroethylene. Males were obtained from a 2-year chronic study (IBT No. 663-08047), following approximately 9 months exposure to 300 ppm Trichloroethylene. Two control groups were utilized in the investi gation; 1 consisting of males approximately 3 months of age (C-I) and 1 consisting of males of a comparable age with the test males (C-II) . The males were mated weekly with 2 untreated virgin females for 8 consecutive weeks. The following results were obtained during the investigation. One test male and 2 C-II males died during the investigation. No other deaths occurred. No untoward behavioral reactions were noted among test or control animals. Parameters of male and female fertility were similar among test and control animals. The numbers of corpora lutea, implantation sites, deciduomata, and viable embryos obtained for the Trichlorethylene treated group compared favor ably with the control groups. Mutation rates regarding the percentage of early deaths along with the comparisons of the numbers of embryos per female in the test group to those of the controls revealed similar findings for the Trichloroethylene treated group and the control groups. 032228 9acupit,Mil B I O - T E S T J.aJtQfycUasU&i', 9hc. 3 It is concluded that exposure to Trichloroethylene via inhalation did not reveal a dominant lethal mutagenic effect in this test system. Respectfully submitted, INDUSTRIAL BIO-TEST LABORATORIES, INC. Report prepared by: Clare Salamon, B.S. Assistant Toxicologist Rat Progeny William Gerstner, B.S. Group Leader Special Projects Sandra Smith / Group Leader Rat Progeny Report approved by: P\ Gerald L. Kennedy, JrV, $.S. Section Head, Toxicology Florence K. Ki&oshite', Pi Technical Manager, 'Toxicology M. L. Keplinger Manager, Toxicology J/ jd SL 032229 Undudi/iiai BIO-TEST Jtabonai&Uei., 9nc. 4 III. Procedure A. Experimental Animals The animals employed were Charles River* strain albino rats. The test group (T-IV) males were obtained from the 2-year chronic study number 663-08047. These animals were exposed to the test material via inhalation for approximately 9 months prior to initiation of the dominant lethal investigation. Two control groups were utilized; C-I consisting of males approximately 3 months of age which, if necessary, could be compared with cumulative control data and C-n consisting of males of a comparable age with the test males. All females employed in the investigation were approximately 3 months of age. The organization of groups is given in Table I. TABLE I TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Organization of Groups Group C-I C-II T-IV Exposure Level (ppm) None None 300 Number of Males 15 15 15 * Charles River Breeding Laboratories, Wilmington, Massachusetts. IJttdu&biial B I O - T E S T Jtah&iaivU&L, JW 5 B. Test Material and Dose Administration The material tested was Trichloroethylene. The test material was administered via inhalation. The test exposures were carried out in a specially-constructed chamber of stainless steel and glass, having a nominal volume of 9.3 m^. The chamber had a rectangular section, and was equipped with pyramid shaped top and bottom sections to encourage uniform distribution of the test atmosphere. The chamber was provided with clean, conditioned air at a rate of 10-15 air changes per hour. Air was exhausted through the bottom of the chamber. The chamber air flow was balanced to maintain a slight negative pressure inside the chamber relative to the outside air. The chamber was fitted with sanitary drain connections to facilitate daily cleaning of the chambers. The test material was metered into the chamber air supply so that it was well-mixed with the incoming air by turbulence. The test material was introduced as a vapor. All test material was supplied by PPG Industries, Inc. The chamber atmospheres were analyzed for Trichloroethylene by gas chromatography at least twice daily. The inhalation portion of the investigation was conducted at the Decatur facilities. The animals were brought to the Northbrook facilities where the reproduction portion was conducted. SL 032231 9*uu6&ual B I O - T H S T J.sMonaiawi, 9nc. 6 C. Reproductive Performance Each male was placed in a cage with 2 untreated virgin females. One week later, the males were removed from these breeding cages and placed in another cage with 2 fresh virgin females. This procedure continued for 8 consecutive weeks, the period of time required for maturation of the male rat germ cells. The females were sacrificed (carbon doxide asphyxiation) 18 days following initiation of cohabitation. An incision was made in the abdominal wall and the full extent of both uterine horns exposed immediately. Fetal swellings, implantation sites, resorption sites (early and late differentiated) , and corpora lutea were recorded. Resportion sites were divided into 2 groups, early deaths (deciduomata) and late deaths. Late deaths refer to embryos which have developed to a relatively advanced stage prior to death, as evidenced by the presence of visible placenta and fetal membranes or remnants thereof. The frequency of late deaths is apparently unaffected by mutagens and, therefore, would appear to be non-genetic in this test system. Deciduomata occur at the sites of implanted blastocysts which fail to develop following implantation. The mutagenicity of the chemical can be measured by the proportions of all implantations which are deciduomata. 032^2 Si-* DttdttiiniaL B I O * T E S T JLaJwiat&u&i., Dwz. 7 Mutagenicity can also be measured by comparing the mean number of viable embryos in the test group to the number obtained in the control group. Calculation of the mutation rate using this criterion assumes that pre-implanta tion losses among non-affected test animals will be essentially the same as losses observed among control animals. Following completion of the mating period, all test males were returned to the Decatur facilities to be placed back on test and all control males were sacrificed. SL 032233 9*tduiinial B I O T E S T labonat&u&L, 9*tc, 8 IV. Results A. Mortality and Reactions One T-IV male died during week 7 of the mating period. Two C-II males died; 1 during week 3 and 1 during week 8. No other deaths occurred. No untoward behavioral reactions occurred among either test or control animals. B. Mating Performance Male and female fertility indices are presented in Table II. Parameters of fertility among both males and females were not altered by the exposure to Trichloroethylene. The indices employed are as follows: Male Fertility Index = ----- Number-of Sires x 100 Number of Males Mated Female Fertility Index = Number of Pregnant Females x 100 Number of Females Mated SL 032234 Hntdudinial B I O - T E S T JlaJxyiat&Uei, 9*tc. 9 Group C-I C-II T-IV TABLE II TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Fertility Data Exposure Level (ppm) Week Number Male Fertility F raction Percent None 1 2 3 4 5 6 7 8 15/15 14/15 15/15 15/15 15/15 15/15 15/15 15/15 100.0 93.3 100.0 100.0 100.0 100.0 100.0 100.0 None 300 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 15/15 15/15 14/15 13/14* 13/14 12/14 12/14 12/14 15/15 15/15 15/15 14/15 15/15 14/14* 14/14 14/14 100.0 100.0 93.3 92.9 92.9 85.7 85.7 85.7 100.0 100.0 100.0 93.3 100.0 100.0 100.0 100.0 Female Fertility Fraction Percent 22/30 20/30 26/30 27/30 26/30 24/30 28/30 27/30 73.3 66.7 86.7 90.0 86.7 80.7 93.3 90.0 26/30 25/30 25/30 24/28 22/28 18/26 (1) 23/28 17/28 86.7 83.3 83.3 85.7 78.6 69.2 82.1 60.7 25/30 26/30 26/30 23/29 (2) 25/30 23/28 25/28 22/28 83.3 86.7 86.7 79.3 83.3 82.1 89.3 78.6 * One male died. (1) Two females delivered prior to sacrifice. (2) One female delivered prior to sacrifice. SL 032235 9*uiuiiual B I O - T E S T Jtaltoteiyuei, 9*tc. 10 C. Sacrifice Data Data pertaining to the numbers of corpora lutea, implantation sites, resorption sites (early and late differentiated) , and viable embryos are presented in Table III. Data obtained from females mated with Trichloroethylene treated males compared favorably with the concurrent control groups. SL 032236 TABLE HI TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats to Reproductive Data W Exposure Number of Implantation Resorption Sites r Level Week females Corpora Lutea Sites Early Late Embryos o Croup (ppm) Number Examined Total Mean Total Mean Total Mean Total Mean Total Mean CO rNo5 Cl CO None 1 2 3 22 315 14.3 293 13.3 15 0.7 4 0.2 274 12.4 20 309 15.5 296 14.8 24 1.2 5 0.3 267 13.4 26 323 12.4 302 11.6 17 0.7 1 0.1 284 10.9 4 27 375 13.8 347 12.8 25 0.9 0 0.0 322 11.9 5 26 328 12.6 290 11.2 24 0.9 1 0.1 265 10.2 6 24 313 13.0 276 11.5 10 0.4 5 0.2 261 10.9 7 28 381 13.6 342 12.2 26 0.9 3 0.1 313 11.2 8 27 357 13.2 330 12.2 11 0.4 0 0.0 319 11.8 C-ll None 1 2 3 4 5 6 7 8 26 368 14.2 338 13.0 16 0.6 1 0.1 321 12.3 25 356 14.2 329 13.2 10 0.4 3 0.1 316 12.7 25 287 11.5 270 10.8 13 0.5 4 0.2 253 10.1 24 305 12.7 292 12.2 20 0.8 5 0.2 267 11.1 22 291 13.2 271 12.3 9 0.4 3 0.1 259 11.8 18 244 13.6 227 12.6 9 0.5 2 0.1 216 12.0 23 295 12.8 282 12.3 6 0.3 1 0.1 275 12.0 17 219 12.9 204 12.0 21* 1.2 2 0.1 181 10.7 T IV 300 1 25 348 13.9 326 13.0 18 0.7 0 0.0 308 12.3 2 26 378 14.5 349 13.4 16 0.6 0 0.0 333 12.8 3 26 310 11.9 298 11.5 11 0.4 5 0.2 282 10.8 4 23 329 14.3 323 14.0 12 0.5 3 0.1 306 13.4 5 25 292 11.7 278 11.1 9 0.4 2 0.1 267 10.7 6 23 312 13.6 292 12.7 17 0.7 2 0.1 273 11.9 7 25 307 12.3 290 11.6 13 0.5 7 0.3 270 10.8 8 22 277 12.6 264 12.0 10 0.5 1 0.1 253 11.5 * One female accounted for 15 resorption sites. I 3kdu&Uial BIO-TEST JtaJi&uzt&uei., 3kc. 12 D. Mutagenic Data A summary of results of the mutagenic study is presented in Table IV. 1. Pre-Implantation loss is calculated as follows: Number of Corpora Lutea - Number of implantation sites x 100 Number of Corpora Lutea 2. The mutation rate is calculated by comparing the number of early resorptions (deciduomata) to the total number of implantations for each group. Number of Early Resorption Sites x 100 (See A in table) Number of Implantation Sites Another way of expressing the mutation rate, which takes into account pre-implantation losses, is to compare the mean number of normal embryos in each test group to the mean number of embryos in the control group. Embryos/Female Control - Embryos/Female Test x 100 (See B in table) Embryos/Female Control Values presented for each group were obtained by comparing the mean values of that group to the values of the C-I group (a in table) and to the C-II group (b in table). Values with a minus (-) sign indicate that the mean number of embryos for that group and week was greater than that of controls. Mutation rates for the Trichloroethylene treated animals compared favorably with those obtained for the concurrent control group. SL 03W38 SncLidiniai B I O - T E S T Jlaltanaiyu&L, 9nc. 13 Group C-I C-II T-IV TABLE IV TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Exposure Level (ppm) Week Number Pre-Implantation Loss A None None 300 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 7.0 4.2 6.5 7.5 11.6 11.8 10.2 7.6 8.2 7.6 5.9 4.3 6.9 7.0 4.4 6.8 6.3 7.7 3.9 1.8 4.8 6.4 5.5 4.7 5.1 8.1 5.6 7.2 8.3 3.6 7.6 3.3 4.7 3.0 4.8 6.8 3.3 4.0 2.1 10.3 5.5 4.6 3.7 3.7 3.2 5.8 4.5 3.8 Mutation Rate B a b _ -0.8 - -5.5 - -7.9 - -7.2 - 13.6 - 9.2 - 6.7 - -10.3 0.9 5.2 7.3 6.7 -15.7 -10.1 -7.1 9.3 _ - 0.8 4.5 0.9 -12.6 -4.9 -9.2 3.6 2.5 0.0 -0.8" -6.9 -20.7 9.3 0.8 10.0 -7.5 SL 032239 Undttdfoial B I O - T E S T JlaJuimt&iiGi, 9*tc. 14 E. Individual Data Mutation rates determined for each male are presented in Tables V through VII. X denotes no females were pregnant during that week. SL 032240 }*tdMbu<aL B I O - T E S T Jalto^aMyuei, Hue. 15 Exposure Level (ppm) TABLE V TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual 5ire Data Sire Number Week Number i 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 Pre-Implantation Loss 30.0 28.6 0.0 0.0 0.0 0.0 0.0 3.6 0.0 0.0 8.0 3.6 42.1 0.0 62.1 13.3 0.0 3.6 0.0 14.8 0.0 14.3 8.3 8.0 40.0 14.3 0.0 IS.8 7.1 21.4 3.7 26.1 A 0.0 0.0 16.0 10.3 4.2 6.7 17.9 0.0 0.0 7.1 0.0 3.7 9.1 0.0 18.2 0.0 12.0 3.7 9.1 17.4 9.1 8.3 27.3 4.3 44.4 11.1 4.3 12.5 0.0 4.5 3.8 0.0 Mutation Rate B a - 43.1 - -18.1 - -4.0 - -8.1 - 2.5 - -16.7 - 4.2 - -26.2 - - -10.2 - -8.9 - -17.1 - 57.6 - 29.2 - 62.5 - -21.5 - 10.6 - -2.4 - 1.0 - 14.4 - 15.3 - 8.3 - 33.3 - -2.8 - 59.3 - -26.0 - -8.9 - -26.1 - -10.2 - 12.5 - 0.0 - 20.6 Of l r SL 032241 HtuinAirUal B I O - T E S T Jlalxyuaio'U&i, jrtc. i Group C-I Exposure Level Copm) None TABLE V continued TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Sire Number S 6 7 8 Week Number 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 Pre-Implantation Loss 10.3 3.1 8.0 3.2 23.1 0.0 3.8 9.4 0.0 X 6.7 4.3 0.0 0.0 8.0 8.3 0.0 0.0 14.8 0.0 24.1 12.5 0.0 4.0 16.7 0.0 11.5 0.0 10.0 0.0 42.2 0.0 A 0.0 9.7 0.0 3.3 5.0 7.7 8.0 3.4 0.0 0.0 4.5 0.0 4.2 13.0 9.1 20.0 0.0 17.4 7.7 0.0 3.6 0.0 8.3 6.7 3.1 13.0 0.0 16.7 0.0 5.3 6.3 Mutation Rate B a b _ -1.6 - -10.2 - -13.9 - -30.6 - 19.5 - 0.2 - 8.3 -30.8 - -30.1 - -38.6 - 5.4 - -10.2 - 4.2 - 16.7 - 6.5 - 2.4 - 5.5 - 5.9 - -8.1 - 6.8 - -4.2 - -12.5 - -2.8 -13.8 - -18.1 - 1.0 -8.1 - 36.4 - -8.3 - 25.0 " 29.9 0322^2 SL 3*tcb*lt%kil B I O * T E S T jlaJi&iat&ii&i, JIttc. Group C-I Exposure Level (ppm) None TABLE V continued TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Sire Number 9 10 11 12 Week Number 1 2 3 4 5 6 7 S 1 2 3 4 5 6. 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 Pre-Implantation Loss 0.0 6.9 4.5 0.0 0.0 0.0 0.0 10.3 0.0 0.0 20.8 9.1 10.7 50.0 8.0 0.0 0.0 0.0 0.0 10.7 22.7 0.0 0.0 10.0 0.0 0.0 14.2 0.0 7.1 20.7 0.0 0.0 A 0.0 0.0 9.5 7.1 0.0 0.0 0.0 0.0 2.9 0.0 5.3 10.0 8.0 0.0 0.0 0.0 0.0 100.0 0.0 0.0 23.5 4.0 20.0 3.7 4.0 3.4 0.0 9.7 0.0 0.0 4.3 4.2 Mutation Rate B a b _ -13.8 - -6.3 - 10.9 - -17.1 - -1.7 - 0.0 - -20.8 " -21.5 - -34.1 - -10.2 - 10.9 - 18.9 - 2.5 - 58.3 - 8.3 - -26.2 * 2.4 - 100.0 - -18.8 - -12.6 - 44.9 - 0.0 * 16.7 - -21.5 - 2.4 - -10.2 - -18.8 - -26.1 - -10.2 - 4.2 - 8.3 -30.8 SL 032243 JndniiiAJai B I O - T E S T daltonsUonjeA.. J?e. 19 Group C-I Exposure Level Coom) None TABLE V continued TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Sire Number 13 14 15 Week Number 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 Pre-Implantation Loss 0.0 0.0 3.7 3.4 0.0 17.9 0.0 0.0 4.0 0.0 0.0 34.8 6.7 33.3 0.0 0.0 22.2 0.0 0.0 7.4 7.1 0.0 0.0 3.3 A 6.3 6.7 3.8 0.0 8.3 13.0 0.0 0.0 0.0 20.0 0.0 13.3 0.0 0.0 8.3 3.8 4.8 0.0 0.0 8.0 34.6 0.0 8.7 3.4 Mutation Rate B a b _ -22.0 - -10.2 - -23.8 - -26.1 - 6.8 - 20.8 - -12.5 - -12.1 _ 6.5 - -18.1 - -23.8 - 41.4 - -18.6 - 25.0 - 8.3 " -16.8 ' - 18.7 - -18.1 - -13.9 - -3.6 - 32.2 - 0.0 - -29.2 -30.8 SL 032244 JhMu&uoL bio-test J.auoAGt&ue*, 20 Grout) c-n TABLE VI TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Exposure Level (ppm) None Sire Number 16 Week Number 1 2 3 4 5 6 7 8 Pre-Implantation Loss 23.5 3.6 4.3 3.6 16.1 X X X 17 ' 18 1 Z 3 4 5 6 7 8 1 Z 3 4 5 6 7 8 0.0 38.9 4.2 17.1 0.0 0.0 4.2 0.0 3.3 6.5 0.0 0.0 0.0 4.0 3.6 22.2 .. 19 1 2 3 4 5 6 7 8 10.0 24.0 0.0 0.0 0.0 40.6 3.8 13.0 Mutation Rate AB a 3.8 -0.8 3.7 3.0 0.0 12.8 7.4 -5.0 3.8 -22.5 0.0 4.5 4.3 6.9 3.6 7.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 4.2 0.0 4.8 7.4 5.3 14.3 7.4 0.0 5.3 0.0 0.0 o --1 1 -21.0 21.6 -0.9 -13.4 -32.4 -19.3 -2.7 2.5 -16.9 -0.7 -5.0 -37.3 -0.9 -20.5 19.5 -0.8 32.8 17.4 -5.0 -27.5 17.4 -11.6 15.3 b - _ - - - - * SL 032245 Stubidllial BIO-TEST jtab&iatosU&i, Sue. 21 Group c-n Exposure Level (ppm) None TABLE VI continued TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Sire Number 20 21 22 23 Week Number 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 Pre-Implantation Loss 14.3 0.0 0.0 X X 8.3 X X 10.0 0.0 14.3 11.5 18.2 0.0 0.0 0.0 3.0 0.0 0.0 0.0 0.0 8.3 3.8 0.0 0.0 0.0 0.0 0.0 10.7 0.0 0.0 7.4 Mutation Rate AB a 5.6 31.5 7.1 3.0 4.2 -0.9 0.0 -0.9 3.7 11.1 8.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 8.7 11.1 8.7 0.0 0.0 100.0 3.6 9.1 0.0 7.7 4.0 0.0 0.0 0.0 -4.8 10.4 -0.9 3.4 11.8 -28.4 -16.1 15.3 -29.0 10.4 3.7 66.4 -2.9 -0.9 -7.1 100.0 -8.9 25.4 -0.9 -0.8 -17.6 -23.9 -33.9 -5.9 b - - _ - - - - - - " * - - - - - - " SL 032246 22 Sndudi/tial B i O - T E S T JlaJttyiaJ&Uei., Group C-II Exposure Level (ppm) None TABLE VI continued TEST MATERIAL; Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Sire Number 24 25 26 27 Week Number 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 Pre-Implantation Loss 0.0 3.8 0.0 0.0 0.0 X 0.0 28.6 7.1 0.0 58.3 11.1 3.8 0.0 3.8 0.0 9.1 0.0 4.3 3.3 25.0 8.3 0.0 3.1 45.0 3.4 20.0 0.0 23.8 0.0 0.0 0.0 Mutation Rate AB a 3.7 -4.8 0.0 10.4 0.0 8.3 0.0 -9.2 0.0 -32.5 0.0 -25.0 0.0 57.6 0.0 0.0 0.0 12.5 0.0 0.0 8.0 6.9 -4.8 -19.4 54.1 45.4 -17.6 -56.0 -2.7 -14.4 10.0 6.7 4.5 24.1 0.0 9.1 11.5 6.5 27.4 -4.5 3.7 7.6 -17.6 8.3 -2.7 -22.9 O CD 45.5 0.0 5.0 0.0 0.0 0.0 0.0 6.7 75.8 -4.5 12.8 16.7 -10.1 19.6 -18.6 b _ - - - - - - SL 032247 2 jnduii'ual B I O - T E S T Xalityiaio'UeA, 9xc. TABLE VI continued TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Croup Exposure Level . _ (ppm) .... Sire Number C-II None 28 Week Number 1 2 Pre-Implantation Loss 0.0 6.3 Male Died 29 1 2 3 4 5 6 7 8 0.0 0.0 0.0 0.0 4.0 0.0 0.0 8.3 30 1 2 3 4 5 6 7 8 0.0 3.4 0.0 0.0 0.0 0.0 33.3 X Mutation Rate AB a 0.0 -29.0 0.0 -11.9 0.0 0.0 5.3 10.0 12.5 3.6 3.7 0.0 10.0 0.0 8.7 0.0 3.8 16.0 0.0 -16.9 -4.5 17.4 -13.4 -2.9 -19.3 -16.1 6.8 -4.8 -4.5 3.7 3.4 -22.5 3.7 28.6 b . - - - - " - - SL 032248 9*tdudiruaL B I O - T E S T <3J>&iata<ue4., !)*a. Group T-rv Exposure Level (ppm) 300 TABLE VII TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Sire Number 4026 4027 4028 4029 Week Number 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 3 1 2 3 4 5 6 7 8 Pre-Implantation Loss 13.3 29.0 10.0 3.6 0.0 X 9.1 0.0 10.0 3.7 4.5 6.9 4.2 3.8 3.6 9.5 6.7 8.7 0.0 0.0 3.4 6.7 0.0 4.0 0.0 6.7 0.0 7.1 80.0 3.4 20.8 4.0 A 7.7 0.0 3.7 3.7 0.0 5.0 6.3 3.7 3.8 4.8 11.1 4.3 0.0 0.0 10.5 0.0 4.8 0.0 6.3 0.0 7.1 0.0 4.2 0.0 21.4 4.8 0.0 100.0 0.0 0.0 4.2 Mutation Rate B a b 3.2 17.9 -19.2 -5.0 -17.6 2.4 13.4 -28.7 -12.6 -1.7 15.2 -27.1 20.8 -40.2 -4.8 6.7 8.3 -0.8 -7.8 -14.7 -20.5 28.0 -5.7 1.6 1.0 -8.1 6.8 -4.2 -12.5 20.6 -12.9 25.4 -0.9 -26.1 -37.3 -10.1 -16.1 2.5 -13.8 21.3 -8.9 -35.1 -18.6 0.0 -8.3 -7.5 -8.9 17.9 8.3 -9.2 100.0 -28.4 15.2 2.5 -9.8 13.4 1.0 -17.1 100.0 -16.7 20.8 -7.5 0322^9 SL 9nduii/uaL B I O - T E S T J.abanat&u&i, Hue. Group T-rv Exposure Level (ppm) 300 TABLE VII continued TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Sire Number 4030 4031 4032 4033 Week Number 1 2 3 4 5 6 7 8 1 2 3 4 5 6 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 3 Pre-Implantation Loss 15.4 0.0 9.1 0.0 16.0 0.0 0.0 7.7 4.0 2.9 0.0 0.0 0.0 0.0 Male Died 0.0 15.6 3.8 6.3 0.0 0.0 0.0 7.7 10.8 8.7 4.0 X 0.0 11.1 0.0 11.5 A 4.5 0.0 0.0 0.0 0.0 0.0 7.7 0.0 8.3 3.0 4.8 18.2 4.3 28.0 Mutation Rate B a b 15.3 -4.5 8.3 16.0 -2.9 -33.0 -7.1 -1.7 14.6 10.2 1.0 9.9 11.0 -20.8 0.0 -12.1 11.3 -19.4 8.3 24.4 -7.8 17.4 10.6 26.0 1.0 18.9 6.8 25.0 7.4 7.4 0.0 0.0 0.0 0.0 6.7 0.0 9.1 4.8 0.0 4.3 6.3 18.2 0.0 -0.8 6.7 -14.8 -26.1 26.5 -10.1 37.5 -1.7 -21.0 25.4 -10.1 -2.9 -37.6 24.1 2.5 -1.6 1.6 -23.8 -35.1 36.4 0.0 41.7 -12.1 -22.0 21.3 -18.8 11.0 -25.0 29.2 -7.5 SL 032250 26 Ondud&ual B I O * T E S T JiaJtotataai&i, 9*tc. Group T-IV Exposure Level (ppm) 300 TABLE VII continued TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Sire Number 4034 4035 4036 4037 Week Number 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 3 Pre-Imp lantation Loss 0.0 0.0 4.0 0.0 7.4 0.0 0.0 0.0 0.0 3.0 0.0 0.0 0.0 3.7 0.0 0.0 5.9 15.6 4.2 0.0 0.0 0.0 0.0 0.0 0.0 6.3 0.0 0.0 0.0 19.2 21.4 10.7 Mutation Rate AB ab 12.5 0.0 0.0 3.8 0.0 3.8 3.8 0.0 15.3 -4.5 -10.1 -0.8 -22.5 -10.1 -11.6 6.8 14.6 -10.2 -18.8 -8.1 -5.9 0.0 -4.2 -2.8 7.1 9.4 4.8 0.0 7.1 19.2 3.7 12.0 -4.8 -8.2 12.8 -34.5 -22.5 3.7 -16.0 6.8 -5.7 -14.2 5.9 -44.1 -5.9 12.5 -8.3 -2.8 12.5 3.7 4.3 0.0 8.3 0.0 3.4. 9.1 -12.9 3.0 12.8 -0.8 -7.8 -19.3 -20.5 15.3 -13.8 -2.4 5.9 -8.1 6.8 -8.3 -12.5 6.5 0.0 6.7 30.0 0.0 8.7 4.8 4.5 0.0 -4.8 -4.5 35.8 -17.6 -2.9 8.3 28.6 -5.9 -5.7 -10.2 30.7 -26.1 11.0 16.7 33.3 -16.8 o^51 S^ 9nduit/iial B I O - T E S T Jla&oAato'ii&i. 'Jtta. 27 Group T-IV Exposure Level (ppm) 300 TABLE VII continued TEST MATERIAL: Trichloroethylene Dominant Lethal Study - Albino Rats Mutagenic Data Individual Sire Data Sire Number 4038 4039 4040 Week Number 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 I 2 3 4 5 6 7 8 Pre-Implantation Loss 7.4 3.3 0.0 0.0 4.5 18.2 0.0 0.0 15.4 0.0 0.0 0.0 0.0 16.1 15.4 0.0 0.0 0.0 12.5 0.0 0.0 0.0 3.8 7.1 Mutation Rate AB ab 8.0 7.3 6.5 0.0 -8.2 -14.2 0.0 -19.3 -28.7 0.0 -17.6 -26.1 0.0 -2.9 11.0 0.0 17.4 25.0 0.0 6.3 12.5 0.0 -10.2 -21.5 0.0 13.3 14.3 0.0 0.0 0.0 0.0 9.1 11.3 3.0 -10.1 -30.3 -17.6 -19.3 1.8 15.3 10.6 -2.4 -18.8 -39.6 -1.7 -8.3 -8.3 6.5 0.0 3.2 2.4 0.0 6.7 1.6 0.0 3.7 -4.0 9.7 -17.6 -26.1 0.0 -17.6 -1.7 7.7 -10.1 0.0 8.0 -2.7 4.2 0.0 -10.2 -21.5 SL 0322S2