1、API TR400 93 W 0732290 05291343 851 W American Petroleum Institute 1220 L Street, Northwest Washington, D.C. 20005 4 Health and Environmental Sciences Department A Preliminary Study of the Effect of Toluene on Pregnancy of the Rat (I n ha I at i on Ex ps u re) JUNE 1993 TOXICOLOGY REPORT NUMBER TR40
2、0 API TR400 93 O732290 0527144 798 M FOREWORD API PUBLICATIONS NECESSARILY ADDRESS PROBLEMS OF A GENERAL NATURE. WITH RESPECT TO PARTICULAR CIRCUMSTANCES, LOCAL, STATE, AND FEDERAL LAWS AND REGULATIONS SHOULD BE REVIEWED. API IS NOT UNDERTAKING TO MEET THE DUTIES OF EMPLOYERS, MANU- FACTURERS, OR SU
3、PPLIERS TO WARN AND PROPERLY TRAIN AND EQUIP THEIR EMPLOYEES, AND OTHERS EXPOSED, CONCERNING HEALTH AND TIONS UNDER LOCAL, STATE, OR FEDERAL LAWS. NOTHING CONTAINED IN ANY API PUBLICATION IS TO BE CONSTRUED AS SAFETY RISKS AND PRECAUTIONS, NOR UNDERTAKING THEIR OBLIGA- GRANTING ANY RIGHT, BY IMPLICA
4、TION OR OTHERWISE, FOR THE MANU- FACTUREi, SALE, OR USE OF ANY METHOD, APPARATUS, OR PRODUCT COV- ERED BY LETIERS PATENT. NEITHER SHOULD ANYTHING CONTAINED IN ITY FOR INFRINGEMENT OF LETTERS PATENT. THE PUBLICATION BE CONSTRUED AS INSURING ANYONE AGAINST LIABJL- The full study, utilizing dose levels
5、 based on this study, can be found in report TR401, “Toluene: The Effect on Pregnancy of the Rat (Inhalation Exposure).“ Addressee: API TR400 93 0732290 0529345 b24 = APT 1/91309 A PRELIMINARY STUDY OF THE EFFECT OF TOLUENE ON PREGNANCY OF THE FUT (INHALATION EXPOSURE) Toluene Developmental Toxicity
6、 American Petroleum Institute, 1220 L Street, Northwest, Washington, D.C. 20005, U.S.A. Workgroup, Report issued: 3 September 1992. Authors : Amanda J. Brooker, Caroline Brennan, David M. John, Derek W. Coombs. Huntingdon Research Centre Ltd., P.O. Box 2, Huntingdon, Cambridgeshire, PE18 6ES, ENGLAN
7、D. API TR400 93 m O732290 052934b 560 m Deparhi. thereafter the pattern of response was similar to that at 3500 ppm. At lower exposures, there was a slight reduction in weight gain following the onset of treatment: from Day 8/10 however, weight gains were comparable with the controls. (e) Terminal p
8、ost mottem examination (Appendix 1) No gross macroscopic findings indicative of an effect of treatment were noted at post mortem examination. There were no consistent treatment-related effects on absolute liver weights at termination, especially when the differing pregnancy status in the groups is a
9、ccounted for. LITTER DATA (Tables 6 and 7, Appendices 7 - 9) At 5000 ppm, there was an increase in both pre- and post implantation loss which culminated in 6/9 pregnant animals losing their entire litters and mean post implantation loss of 52% in the remaining 3 litters. Day 20 sacrifice. were marke
10、dly reduced. foetuses at termination revealed marked subcutaneous oedema in 1 foe tus. Litter size was approximately half that of the controls at Litter and mean foetal weights in surviving litters Gross macroscopic examination of the 20 At 3500 ppm and, to a lesser extent 2000 ppm, there was a slig
11、ht increase in embryonic losses (with subsequent increase in post implantation loss) resulting in a marginally lower litter size. Litter weight was lower than controls at both concentrations: mean foetal weight was reduced at 3500 ppm only when compared with the controls, 14/15 foetuses in one litte
12、r and 1/15 foetuses in a second litter at 3500 ppm had craniofacial abnormalities. :8: API TR400 93 W O732290 0529163 b4T APT/ 1 At 500 and 1000 ppm, there were no adverse effects of exposure to Toluene on embryonic development as assessed in this study. 2/13 foetuses in one litter at 1000 ppm had c
13、raniofacial abnormalities. :9: API TR4OO 93 = O732290 0527364 58b 1 APT/ 1 FIGURE 1 Water consumption of pregnant females - group mean values 0 Control 0 Toluene, 000 ppm Toluene, 3500 ppm a Toulene, 500 ppm a Toluene, 2000 ppm Toluene, 5000 ppm Water consumption g/rat/day) 50 40 30 20 10 during Da)
14、. Water consumption (g/rat/day) 30 20 10 I -. .4-5 6-7 8-9 dux I 18 - 19 Da- Treatment period: Days 6 to 15 of pregnancy inclusive Inclucles females showing total resorption : 10 : ru API TR400 93 m 0732290 05291b5 412 m APT/ 1 EE li i; 1: i; 1: Total resorption - - - - - Non-pregnant - With live yo
15、ung Day 20 11 10 11 12 10 3 : 13 : API TR4OO 93 O732290 05291bA 121 = APT/ 1 TABLE 2 Water consumption - animals with live young - group mean values Group : Compound : Dosage (ppm) : ;roup - 1 2 3 4 5 6 - Number of anima 1 s 11 10 11 12 10 A=9 B=3 1 2 3 4 5 Control Toluene 5 O0 1000 2000 3500 5000 -
16、 6 Water consumption (g/rat/day) during Days of gestation 0-1 2-3 4-5 6-7 8-9 10-11 12-13 14-15 16-17 18-19 35 362 352 362 35 39 38 42 46 48 29 33 31 31 33 35 37 42 44 42 30 32 30 30 31 36l 37 40 44 41 29 32 31 33 37 44 45 49 51 45 30 32 33 28 40 53 63 69 70 64 29 32 30 33 53 70 70 75 87 59 28 33 33
17、 36 62 80 70 80 99 65 Superscript indicates the number of values excluded Treatment period Days 6 to 15 of pregnancy inclusive : 14 : API TR400 93 0732290 0529169 Ob8 D Group APT/ 1 Number Food consumption (g/rat/day) during Days of gestation animals 0-1 2-3 4-5 6-7 8-9 10-11 12-13 14-15 16-17 18-19
18、 of TABLE 3 Food consumption - animals with live young - group mean values Group : 1 2 3 4 5 6 Compound : Contr o 1 To luene Dosage (ppm) : - 5 O0 1000 2000 3500 5000 11 10 11 12 10 A=9 B=3 24 23 25 26 26 27 27 27 28 27 22 24 25 25 27 28 27 28 29 27 22 23 25 23 24 26 26 28 30 27 21 23 24 21 22 23 24
19、 25 29 27 22 22 24 16 19 21 23 24 26 25 23 23 24 16 18 19 21 23 28 25 22 22 24 17 19 21 21 24 28 25 Treatment period Days 6 to 15 of pregnancy inclusive : 15 : API TR400 93 m 0732290 0529170 88T m TABLE 4 Bodyweights - animals with live young - group mean values Group : 1 2 3 4 5 Compound: Control T
20、oluene Dosage (ppm) : - ;roup - 1 2 3 4 5 6 - Jumber of inimalc 11 10 11 12 10 Ao9 Ba3 I . APT/ 1 6 - 500 1000 2000 3500 5000 Bodyweight (g) at Day of gestation O 2 4 6 8 10 12 14 16 18 20 226 244 253 265 274 283 295 306 322 346 374 226 241 251 264 271 282 295 306 323 348 375 226 241 251 264 270 279
21、1 292 303 318 344 371 224 237 247 259 259 264 274 283 296 323 349 223 239 249 258 248 250 255 264 274 300 327 225 239 250 261 254 249 255 2591 259 274 285 221 234 244 255 251 247 256 2621 264 285 299 1 Treatment period Days 6 to 15 of pregnancy inclusive Excludes one animal with spurious weight : 16
22、 : API TR4OO 93 0732290 0529171 7Lb APT/ 1 TABLE 5 Liver weights - group mean values Group : 1 2 3 4 5 6 Compound : Control Toluene 5 O0 1000 2000 3500 5000 Dosage (ppm) : - Group Number Weight at Day 20 11 10 11 12 10 A=9 B= 3 374 16.54 . 375 16.50 371 16.15 3 49 15.83 327 14.89 285 15.02 299 15.66
23、 : 17 : API TR400 93 0732290 O529372 652 m d 3 fi 8 9 O L, bo I Q U Q a L, o) U U 4 d rn U m N d 9 s O O O O VI O O rn m O O O N O O O d O O VI I n Y k al bo 6 O op n : 18 : m m m u) U rn U u) QI O h ro m . d U U u) O 4 O in O O 2 1 4 d r) 2 a3 cv m d rn h U m U m h VI U . d . m (o O O O . ro O 01 ob d in . ril a) . 2 m N m N 4 Cu U N O u) rc1 O m 4 VI m “t O O O 1 O 9 m d 1 m d s in d 6 Cu m Qi + QI m h 4 O u) m . z! io a) O 4 VI O . 1 O I- d r) * 1 m d ob 5, O f- N a) QI m m a) h m VI u) cy 4 U O 4 VI d ? O O U N r) -4 4 d d . (o d APT/ 1
