Document rpn7w0veO4YX8j02D39LkL6B0

Roproductln and Teratology Studies with Three Polychlorinated Biphenyls in Albino Rats Otis E'. Fanchcr^, M. L. Keplinger, J. B. Plank, E. P. Wheeler^ and J. C. Calandra Industrial BIO-TEST Laboratories, Inc. Northbrook, Illinois Running Title; Reproductive Studies with 3 PCB's in Albino Rats. * Present Address; 624 N. Abrcgo Drive, Green Valley, Arizona 85&14, to whom proofs are to be sent, ^ Monsanto Company, St. Louis, Missouri. MOMS 066926 ABSTRACT Reproduction and Teratology Studies with Three Polychlorinated Biphenyls in Albino Rats. Fancher, Otis E., Keplinger, M. L. , Plank. J. B. , Wheeler, E. P, , and Calandra, J. C. (0000), Toxicol, Appl. Pharmacol. 00. 00 - 00, Three generation reproduction studies and teratology studies were conducted with 3polychlorinated biphenyls (Aroclors 1242, 1254 and 1260) in albino rats. Aroclor 1242 at a <2. dietary level of 100 ppm adversely affected mating and incidence of pregnancy during the second generation. Except fora suggestion of some decrease in the Inclination to mate among other groups fed 10 or 100 ppm of the test materials during the second and third genera tions, no other reproductive parameter was affected. None of the materials was jxidgod to be teratogenic at dosage levels of 10 and 30 mg/kg. MCNS 066927 INDEX TERMS Aroclors Aroclor 1242 Aroclor 1254 Aroclor 1260 Polychlorinated Biphenyls Reproductive effects of, in albino rats Teratology study of, in albino rats HONS 046928 Reproduction and Teratology Studies with Three Polychlorinated Biphenyls1 in Albino Rat s Otis E, Fancher^, M. L. Keplinger, J, B. Plank, E. P. Wheeler3 and J. C. Calandra Industrial BIO-TEST Laboratories, Inc, Northbrook, Illinois Reproduction and Teratology Studies with Three Polychlorinated Biphenyls in Albino Rats. Fancher, Otis E., Keplinger, M. L. , Plank, J. B, , Wheeler, E. P. , and Calandra, J. C. (0000). Toxicol. Appl. Pharmacol. 00, 00 - 00. Three generation reproduction studies and teratology studies were conducted with 3 polychlorinated biphenyls (Arcolors 1242, 1254 and 12&0) in albino rats. Aroclor 1242 at a dietary level of 100 ppm adversely affected mating and incidence of i pregnancy during the second generation. Except for a suggestion of i some decrease in the inclination to mate among other groups fed 10 or 100 ppm of the test materials during the second and third genera tions, no other reproductive parameter was affected. None of the materials was judged to be teratogenic at dosage levels of 10 and 30 mg/kg. Background toxicological information has been summarized by Fanchcr et al, (0000) in the introductory paper of this series. Be cause of the demons!rated reproductive effects of polychlorinated MONS 066929 biphenyls in various avian species and in view of the reported occurrence of^eak deformities in chicks hatched from eggs treat ed with Aroclor 1242, the present study was conducted for assess ment of reproductive and teratogenic effects of 3 Aroclors in a standard mammalian species. METHO DS A. 3-Generation Reproduction Study The animals employed were weanling albino rats of the Charles River strain(Charles River Breeding Laboratories, North Wilming ton, Mass.). A control group and 9 treatment groups, each consist ing of 8 male and 16 female animals, were employed, 3 treatment groups for each of the 3 Aroclors studied. All diets were prepared fresh each week by mixing the appropri ate Aroclor at levels of 1, 10 and 100 ppm with a standard pulver ized stock ration(Spccial Mix Mouse Chow, Ralston Purina Company, St. Louis, Missouri). The control animals wore fed the basic ration alone. Both food and water were available ad libitum. Except during mating trials, each animal was individually housed. All parental animals in all groups were maintained on the appropriate diets with out interruption until sacrifice which followed weaning of the Fb (second) litters. Initially the body weight of each parental animal was determined and all animals were weighed weekly until mating trials began. No further weights were determined except for terminal weights just 066930 HONS prior to sacrifice. Parental animals were observed daily for mort ality and behavioral reactions. Mating trials were initiated with each generation when the animals were 100 days old. Tho 16 females in each group were caged in pairs and mated with a male randomly selected from within the same group. Daily observations for evidence of copulation (copulatory plug or vag inal blood) wore made and the male was removed if, during the next estrous cycle of five days, no further signs of mating were observed. \C Any male failing to mate within ft^n days was replaced by another male from the same group. Females were permitted access to a maximum of 3 males. Mating Indices and Fertility Indicies were calculated. All pups at birth were examined for gross physical abnormal ities and the numbers of viable and stillborn pups of each litter were recorded. Records of survival at designated intervals during the lactation period were maintained and litters of more than 10 pups were reduced to that number by random sacrifice on the fifth day of the lactation period. Lactation, Live Birth and Survival Indices were calculated. A final examination for physical abnormalities was made at weaning. The Fa (first) litters were weaned 21 days postpartum and the parental females were again mated after 10 days to obtain Fb(sccond) litters. Eight males and 16 females from the Fb progeny of each group were selected at weaning for use as parental animals for the next generation. * MGNS 066931 A gross autopsy was performed on any parental animal which died during the study and tissues were preserved for microscopic examination when feasible. After weaning of the Fb litters, parental animals were sacrificed after determination of final body weights. All males and 8 females from each group were subjected to gross patho logic examination. The weights of the liver, kidneys, spleen, gonads, heart and brain were recorded and organ to body weight and organ to brain weight ratios were calculated. Microscopic pathologic studies were conducted on tissues from .< s" fiye male and fhye female parental animals from the control group and from each high treatment level group except for the F2 parents treated with Aroclor 1242. In this case tissues from parental animals treated at the intermediate level wero examined. B. Teratology Study - Albino Rats The animals employed were female Charles River albino rats bred at the Charles River Breeding Laboratories, North Wilmington, Mass. These were confirmed pregnant by sperm-positive results of vaginal examination and were shipped on Day One of gestation, Day Zero being the day of insemination. A control group and 6 treatment groups (treatment levels of 10 and 30 mg/kg/day for each of the Aroclors) were employed, each consisting of 26 animals. The test materials were administered orally as solutions in corn oil using a hypodermic syringe equipped with a ball-tipped intubation needle. Solutions were prepared daily *0NS 066932 in concentrations such that all animals received equivalent quantities of corn oil on a mg/kg basis. Control animals were treated with corn oil alone. All animals were treated once daily,from the sixth through the fifteenth day of gestation (lOdoses). Food and water were available ad libitum. All animals were weighed daily during the dosing period and just prior to sacrifice. Daily records of mortality and reactions were maintained. - All females were sacrificed by carbon dioxide asphyxiation on the 20th day of gestation. An incision was made in the abdominal wall and the full extent of both uterine horns was exposed. Fetal swellings, implantation sites and corpora lutea were counted, special attention being paid to resorption sites or any other uterine abnormalities. The number of viable fetuses present in the uterus was determined, spontaneous movement and a more ruddy color distinguishing live from dead animals. Each fetus was removed by placing a small hcmost&t on the umbilical cord, flush with the abdominal wall, and cutting the cord distal to the clamp. Blotting paper was used to remove excess J*' amniotic fluid and blood prior to weighing the animals. External examinations were made for detection of abnormalities which might include hydrocephaly, exencephaly, meningoencephalocele, simple meningocele, anophthalmia, microphthalmia, cleft lip, man dible or palate, oblique facial cleft, micrognathia, external ear abnormalities in si/.e, shape or position, unusual size or position of HONS 066933 the limbs, number and disposition of the digits, umbilical hernia, gastroschisis, myelomeningocele, spina bifida and scoliosis. Two-thirds of the fetuses from each litter were examined for skeletal development using the alizirin red staining technique de scribed by Hurley (1965). Internal development of the remaining fetuses was evaluated using the free-hand razor blade sectioning technique of Wilson and Wark&ny (1965). RESULTS Statistical treatment of all data analyzed consisted of Analysis of Variance followed by application of "t"-tcsts to any significant dis closures. A. 3-Generation Reproduction Study No effect on body weights of cither parental animals or weanlings was observed among any group of any generation. No behavioral reactions were observed and mortality was unaffected. Pathologic examination of the occasional animal which died during the study failed to reveal any relationship between ingestion of the Aroclors and the death of the animals. No gross pathologic findings among parental animals could be re lated to the ingestion of test materials. Evaluation of organ weight and organ to body weight and organ to brain weight ratio data disclosed several randomly occurring intergroup differences* Only those effects related to the liver might be attributed to treatment with the Aroclors. There is an indication that the tliVoe materials a! the level of 100 ppm MOWS 066934 may cause increased liver weights and increases in liver to body weights and/or liver to brain weight ratios. These effects, if they are real, were moderate in degree and inconsistent in pattern with respect to dose level, sex and generation. It has been shown in a chronic rat study (Fanchcr et al. , (0000) that each of the Aroclors caused liver effects at a dietary level of 100 ppm,butthe effects were delayed in development, being apparent at the 24-month, but. not *4 at the 12-month or earlier sacrifices. In the present studyj the animals were treated for approximately 6 months only. No changes which could be correlated with treatment were observed among tissues from sacrificed parental animals. Findings for treated animals were essentially the same as those for control animals. Focal epithelial hyperplasia of the bladder was noted among some F2 animals; one control female, one male treated with Aa&clor 1212 at 10 ppm, one male and 2 females (from the same litter) treated with Aroclor 1254 at 100 ppm, and one female treated with Aroclor 1260 at 100 ppm. This hyperplasia was associated with focal cystitis and, in some cases, with mineralized calculi. Mating indicies were somewhat decreased by all tl\*cc materials at levels of 10 and 100 ppm, particularly during the second and third generations, being most evident with Aroclor 1242 at the 100 ppm level. In this case also the incidence of pregnancy was low and since only two females produced F2b litters, it was not possible to continue this level through the third generation. Data for reproduction perform- MGNS 066935 ance arc presented in Table 1, The number of live prtps per litter born was not affected for any treatment group, and all pups delivered appeared normal. Erratic variations were observed in the number of pups weaned per litter but no consistent compound or dose correlation was apparent. Weanling body weights were normal for all groups and gross examination at weaning disclosed no external abnormalities. Survival data are pre sented in Table 2, B. Teratology Study Maternal body weights and weight gains were slightly decreased by treatment with Aroclors 1254 and 1260. These data are given id Table 3. No dose-effect correlation was apparent. No deaths occurred among animals of any group and no abnormal reactions were noted. ' Tlie results of the sacrifice on Gestation Day 20 are presented in Tabic 4, Animals in all groups were free of gross uterine ab normalities. There is a suggestion that the Aroclors may exert some effect on the incidence of resorptions but the slight magnitude of any effect and the absence of any clcar-cut dose correlation make this of doubtful significance. No other reproductive parameter affected. was None of the materials at. either level affected fetal body weights or sex ratios. All fetuses appeared normal and were free of gross abnonnal- HONS 06M3* itios. Data regarding fetal skeletal development are summarized In Table 5. None of the materials had an effect on skeletal development at either treatment level, Examination of fetuses for internal development revealed atria of abnormal sire among the progeny from all groups. The incidence of this abnormality did not differ significantly among the control and teat groups. Twelve percent of the fetuses from dams treated with \ Aroclor 1254 at the dose level of 30 mg/kg had caudal renal ectopia,,^ This abnormality was not seen among the progeny of any other group. / / Data with respect to fetal internal development are summarized in ' ` Table 6. DISCUSSION V .J Aroclor 1242 at a dietary level of 100 ppm adversely affected 0 mating and the incidence of pregnancy among albino rats during the second generation of a scheduled 3-gencration study, Except for a suggestion of decreased inclination to mate among other groups fed 10 or 100 ppm of the test materials during the second and third gen erations and some erratic variations in pup survival to weaning age, no other reproductive parameter was affected. None of the materials arc judged to be teratogenic in albino rats at levels of 10 and 30 mg/kg. The non-occurrence of renal ectopia with 10 mg/kg of Aroclor 1254 or among the progeny of rats treated at either level with the closely related Aroclors makes it doubtful that this defect is a spcrific teratogenic response. HONS Q6693? TABLE 1 Reproductive Performance of Albino Rats Treated with Aroclors 1242, 1254 and 1260 Dietary Level (ppm) Litter Meting Index Fraction Percent Incidence of Pregnancy Fraction Percent Fertility Index Fraction Percent Incidence of Parturition Fraction Percent NoneControl Aroclor 1242 1 10 100 Fla Fib F2a F2b F3a F3b Fla Fib F2a F2b F3a F3b Fla Fib F2a F2b F3a F3b Fla Fib F2a F2b 17/25 15/20 16/37 14/26 15/66 12/16 16/37 15/21 15/27 15/18 13/77 9/23 16/43 16/24 13/53 13/24 16/43 16/28 15/43 15/24 11/78 2/37 68.0 75.0 43.2 53.8 22.7 75.0 43.2 71.4 55.6 83.3 16.9 39. 1 37.2 66.7 24.5 54.2 37.2 57. 1 34. 9 62.5 14. 1 5.4 16/16 15/15 14/16 14/14 13/16 12/12 16/16 15/15 15/16 14/15 9/16 8/9 16/16 16/16 12/16 12/12 16/16 15/16 15/16 15/15 7/16 2/7 100 100 87.5 100 81.2 100 100 100 93.8 93.3 56.2 88. 8 100 100 75.0 100 100 93.8 93.8 100 43.8 28.6 16/17 15/15 14/16 14/14 13/15 12/12 16/16 15/16 15/15 14/15 9/13 8/9 16/16 16/16 12/13 12/13 16/16 15/16 15/15 15/15 7/11 2/2 94.1 100 87.5 100 86.7 100 100 93.8 100 93.3 69.2 88.9 100 100 92.3 92.3 100 93. 8 100 100 63.6 100 15/16 15/15 14/14 14/14 11/13 11/12 16/16 15/15 15/15 14/14 9/9 8/8 15/16 16/16 12/12 12/12 15/16 15/15 14/15 15/15 7/7 2/2 93.8 too 100 100 84.6 91.7 100 100 100 100 100 100 93.8 100 100 100 93.8 100 93.3 100 100 100 . ` iitji. o-Vvi i 'r - J > x.r / /' IK 'Vk L, vr ^' HONS 0 6 6 9 3 8 TABLE 1 (Continued) Reproductive Performance of Albino Rats Treated with Aroclors 1242, 1254 and 1260 Dietary Level (ppm) Litter Mating Index Fraction Percent Aroclor 1254 i 10 100 Fla Fib F2a F2b F 3a F3b Fla Fib F2a F2b F3a F3b Fla Fib F2a F2b F3a F3b 16/29 16/29 16/42 11/28 18/58 14/24 16/23 16/21 14/63 11/32 16/54 14/35 16/28 16/26 14/73 10/52 11/36 8/31 55.2 55.2 38. 1 39.3 31.0 53. 3 69.6 76.2 22.2 34.4 29. 6 40. 0 57. 1 61.5 18.2 19.2 30.6 25. 8 Incidence of Pregnancy Fraction Percent 16/16 16/16 12/16 11/12 12/18 11/14 16/16 16/16 11/16 10/11 14/16 13/14 16/16 16/16 13/16 9/13 11/11 8/8 100 100 75. 0 91.7 66.7 78. 6 100 100 68. 8 90.9 87.5 92.9 100 100 81.2 69.2 100 100 Fertility Index Fraction Percent 16/16 16/16 12/16 11/11 12/16 11/12 16/16 16/16 11/14 10/11 14/16 13/14 16/16 16/16 13/14 9/10 11/11 8/8 100 100 75. 0 100 75.0 91.7 100 100 78.6 90.9 87.5 92.9 100 100 92.9 90. 0 100 100 Incidence of Parturition Fraction Percent 16/16 15/16 12/12 11/11 9/12 11/11 16/16 15/16 10/11 9/10 12/14 13/13 15/16 13/16 13/13 9/9 10/11 8/8 100 93. 8 100 100 75.0 100 100 93. 8 90.9 90. 0 85.7 100 93. 8 81.3 100 100 90.9 100 MGNS 0 6 6 9 3 9 TABLE 1 (Continued) Reproductive Performance of Albino Rats Treated with Aroclors 1242, 1254 and 1260 Dietary Level (ppm) Litter Mating Index F raction Percent Incidence of Pregnancy Fraction Percent Fertility Index Fraction Percent Incidence of Pa rturition Fraction Percent Aroclor 1260 i 10 ICO Fla Fib F2a FZb F3a F3b Fla Fib FZa FZb F3a F3b Fla Fib F2a F2b F 3a F3b 16/Z5 16/21 13/53 13/25 17/69 12/29 17/42 16/23 12/54 10/28 13/63 12/34 14/53 14/31 16/54 12/32 16/52 12/40 64. 0 76. 2 24.5 52. 0 24. 6 41.4 40. 5 69.6 22.2 35.7 20. 6 35.3 26.4 45.2 29.6 37.5 30. 8 30. 0 16/16 16/16 13/16 12/13 11/16 10/11 16/16 16/16 12/16 10/12 12/16 11/12 14/16 14/14 13/16 12/13 13/15 10/10 100 100 81.2 92.3 68.8 90.9 100 100 75. 0 83. 3 75. 0 91.7 87. 5 100 81.2 92. 3 86.7 100 16/16 16/16 13/13 12/13 11/17 10/12 16/17 16/16 12/12 10/10 12/13 11/12 14/14 14/14 13/16 12/12 13/16 10/1? 100 100 100 92.3 64.7 83. 3 94. 1 100 . 100 100 92. 3 91.7 100 100 81.2 100 81.2 S3. 3 16/16 15/16 13/13 12/12 10/11 10/10 16/16 16/16 12/12 10/10 12/12 11/11 13/14 14/14 13/13 11/12 12/13 10/10 100 93.8 100 100 90.9 100 100 100 100 100 100 100 92.9 100 100 91.7 92.3 100 Note: Mating Index = Number of Copulations3- X joo Number of Lstrus Cycles Req'd. Fert ility Index : No. of Pregnancies No. Of C opulations 100 Incidence of _ No. of Pregnancies X 100 Pregnancy ' No. of i einaies Mated Incidence of Pa rturition No. of Parturitions X 100 No. of Pregnancies Only one copulation was counted during one estrous cycle of 5 days. HONS 0 6 6 9 4 0 TAB LE 2 Survival Indices of Progeny of Albino Rat3 Treated with Aroclors 1242, 1254 and 1260 Dietary Litter Level (purr.) None - Fla Control Fib F2a F2b F3a F3b Aroclor 1242 Fla Fib i F2a F2b F3 a F 3b Fla Fib 10 F2a F2b F3a F3b Fla 100 Fib F2a F2b Live Birth Index 92.7 93.4 95.2 100 90.2 85. 3 94. 6 92. 8 97. 5 95.5 87.2 88. 8 98. 3 93. 1 93.7 96. 3 85.2 94. 1 92. 9 98.5 84. 9 80. 3 24 - Hour Survival Index 88. 5 98.9 94.3 99. 3 97.8 97.8 98. 3 97. 2 98.7 95. 0 92. 0 93. 0 98. 3 99. 5 92.4 99. 2 99. 2 95. 0 95. 5 98. 0 82. 2 93. 8 5 - Day Survival Index 42.4 65.7 64. 3 82.3 75. 0 85. 0 59.2 82.2 69.5 71.4 61. 3 63.4 ' 76.9 80. 3 81.4 86.4 82.7 74. 4 85. 3 66. 5 80.0 93. 8 Lactation Index 93.9 64. 1 81.2 73.9 78. 5 56. 0 97. 8 71.7 76. 8 74.4 64. 1 51. 1 91. 5 79. 1 85.6 71. 8 99.0 85. 3 77. 9 53.2 97.2 84.6 HONS 0 6 6 9 *1 / /. C'. ^ L TABLE) 2 (Continued) Survival Indices of Progeny of Albino Rats Treated with Aroclors 1242, 1254 and 1260 Dieta.1 / Level (ppm) Litter Aroclor 1254 i 10 100 Fla Fib F2a F2b F3a F3b Fla T lb F2a F2b F3a F3b Fla Fib F2a F2b F 3a F3b Live Birth Index 99.5 97.6 100 97.6 82.4 92.5 90.8 90. 1 94.8 98.9 93.9 89. 0 100 93.3 88.7 84. 5 81. 1 95.2 Z4 - Hour Survival Index 97.8 78.7 99.2 99.1 84.3 100 96.6 91.9 71.7 75.8 98.9 ?4. 3 94.6 97.4 88.2 74.4 70. 1 97. 5 5 - Day Survival Index - 88.7 91.6 90. 2 85. 1 81.4 95. 5 77.0 86.7 58.7 ' 50. 0 95.7 88.6 58.7 72.4 64. 7 53.7 18. 2 49.4 Lactation Index 93. 1 78. 8 83. 0 88. 1 83.7 90. 5 83.7 85. 5 84. 0 94.6 80. 5 84.2 69. 6 25.7 62.7 62. 5 64. 3 51. 3 2 V 6 9 9 0 SNOW TABLE 2 (Continued) Survival Indicies of Progeny of Alb?no Rats Treated with Aroclors 1242, 1254 and 1260 Dietary Level (?om) Litter Aroclor 1260 i 10 100 Fla Fib F2a F2b F 3a F>b Fla Fib F2a F2b F3a F3b Fla Fib F2a F2b F3a Fjb Live Birth Index 97. 1 91.9 99.2 100 90. 8 98. 9 99.5 98. 1 99.2 99. 1 93. 1 93. 5 98. 8 85. 6 97. 8 99. 2 66. 4 89. 8 24 - Hour Survival Index 97.5 100 98.4 100 96.2 98. 9 98. 4 99. 5 91.7 96. 5 81.9 95. 3 91.2 94. 2 90. 1 83. 9 98. 9 97.7 5 - Day Survival Index 76.8 82.9 83.6 77.9 7.4.7 70.8 96.2 97. 1 86. 0 67.0 71.3 51.2 67.8 69. 3 81. 1 88. 1 90.5 75. 0 Lactation Index 93. 0 60.2 93.2 83.5 74. 1 93. 0 95. 9 87.7 80.6 85. 7 83. 0 78. 6 90.2 7 5.6 76. 8 83. 8 84. 350. 8 Note: Live Birth _ No . of Viable Pups Born Index Total No, of Pups Born A 5-Day . No. of Pups Viable at Day 5v 100 Survival Index No. of Viable Pups Born . 100 24-Hour _ No. of Pups Viable at Day I Survival Index No, of Viable Pups Born * Lactation No. of Viable Pups at Day 21 ^ Index " No. of Pups Viable at Day 5 X MOMS 0 6 6 9 4 3 TABLE 3 Body Weight Data, for Gravid Albino Rats Treated with Aroclors 1242, 1254 and 1260 Test Material None Aroclor 1242 Aroclor 1254 Aroclor 1260 Dosage Level (mgr/k?) 6 - 208 10 210 30 - 190 10 204 30 204 10 198 30 195 Body Weight (grams) on Ge station Day 9 12 15 Total Weight Gain 20 (grams) 228 226 203 211 209 206 200 255 273 245 273 211 213 244 238 228 242 237 255 231 . 247 312 344 309 ' 275 292 283 280 104 134 119 71 88 85 85 % O 9 ,V69<>0 Test Material None Aroclor 1242 Aroclor 1254 Aroclor 1260 TABLE 4 Reproductive Effects of Aroclors 1242, 1254 and 1260 in Albino Rats Dose Level (mg/kg) -- F emales Examined 26 C o rpo ra Lutea mean/female 11. 7 inplantation Resorption Sites Sites mean/female mean/female 10. 3 0.5 Viable Females with Fetuses one or more mean/femaleresorptions I percent 9. 8 23. 1 10 22 12.2 30 20 12.0 10 18 10.7 30 18 11.6 10 17 12.4 30 19 11.7 11. 1 11. 0 9.5 10.2 11.2 10.7 0.7 0.2 .0.7 0.8a 0.5 1.2b 10.4 10. 8 8.8 9.4 10.8 9.5 54. 5 15.0 61.1 44.4 29.4 57. 9 One female had six resorption sites. b One female had 12 resorption sites. % o z v> s*e><>90 HONS 0 6 6 9 4 6 TABLE 5 Skeletal Development of Progeny of Albino Rats Treated with Aroclors 1242, 1254 and 1260 Test Dose Material Level A mg/kg I p None Aroclor 1242 Aroclor 1254 Aroclor 1260 --8 10 1 30 1 4.7 0.8 0.7 10 2a 30 1 1.8 1. o 10 i 30 1 0.8 0. 9 B IP FINDINGS C IP 30 17.8 23 13.6 5 3.8 5 3. 8 15 10. 5 22 15.4 12 10.6 22 19.5 21 20.4 17 16. 5 20 15. 5 9 7. 0 21 18.6 15 13.3 A - Supernumerary ribs 3 - Incomplete ossification of sternum section (s) C - Non-ossificd sternum section, (s) D - Underdeveloped frontal and parietal skull bones Z - Abnormal fetuses F - Normal fetuses I - Incidence P = Percent a Angulated ribs D IP 1 0.6 -- __ --" -- --. -- -- -- __ --- --- E I P. 58 34. 3 11 8.4 37 25.9 33 29.2 37 35.9 27 20. 9 31 27.4 F IP 111 65.7 120 106 91.6 74. 1 80 70.8 66 64. 1 102 79. 1 82 72.6 TABLE 6 Internal Development of Progeny of Albino Rats Treated with Aroclors 1242, 1254 and 1260 Test Material Dose Level mg/It- None --- Aroclor 1242 10 30 Aroclor 1254 10 30 Aroclor 1260 10 30 Findings Small atria Large atria Umloscendcd testes Small atria Large atria One small testicle Small atria Large atria One small testicle Small atria Large atria Small atria Large atria Caudal renal ectopia. Small atria Large atria . . Moderate internal hydrocephalus . Small atria Large atria . Inc idence Percent 6 7. 1 7 8.2 Z 2.4 4 4. 1 12 12.Z Z 2.0 Z 2. 7 11 15. 1 3 4. 1 .i 2. 1 10 21.7 5 7. 6 1 1. 5 3 12. 1 1 1.9 11 20.4 1 " 1.5 11 16.4 5 7. 5 MGNS 0 6 6 9 4 7 FOOTNOTES * Aroclors 1242, 1254 and 1260. Monsanto Company, St. Louis, Missouri ^ Prosont address; 624 N. Abrogo Drive, Green Valley, Arizona 85614 ^ Monsanto Company, St. Louis, Missouri MOSS 066948 REFERENCES Fancher, Otis E. , Koplingcr, M.L., Wheeler, E. P, and Calandra, J, C. (0000). ToxicologicaLstudies of three polychlorinated biphenyls. Toxicol. Appl. Pharmacol. 00. 00 - 00. Fanclier, Otis E, , Kcplinger, M. L. , Plank, J. B. , Wheeler, E. P. , and Calandra, J. C. (0000). Chronic toxicity of three polychlorinated biphenyls in albino rats. Toxicol. Appl. Pharmacol. 00, 00 - 00. Hurley, L. S. (1965). Demonstration A-alizirin staining of bone. Supplement Co Teratology Princi pics and Techniques pp. 121 - 122. Berkeley, California. Wilson, J. G. and Warkany, J. (1965). Teratology Principles and Techniques pp,271 - 277. Univ. of Chicago Press, Chicago, Illinois. *GNS 066949