The weeks shown in color represent the start and end points of chemical exposure for each study.

Study Results Study Details References

Results for Dioxin (TCDD)

Decreased percent normal cyclicity (transition to reproductive senescence) at age 9 and 11 months for 0.05 μg/kg/wk dose

Subjects: Sprague-Dawley rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.001, 0.005, or 0.05 μg/kg/week

Other doses tested: 0.2 μg/kg/week

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 14 and weekly through adulthood – adulthood (comparable to human prenatal development from approximately day 1 of week 6 to beyond birth)

Age of measurement: 2 through 12 months of age

Reference [PubMed Link]
Shi ZQ, Valdez KE, Ting AY, Franczak A, Gum SL, Petroff BK. 2007. Ovarian endocrine disruption underlies premature reproductive senescence following environmentally relevant chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biol Reprod 76(2):198-202.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased in vitro estradiol secretion

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: birth through 21 days of age

Reference [PubMed Link]
Chaffin CL, Trewin AL, Watanabe G, Taya K, Hutz RJ. 1997. Alterations to the pituitary-gonadal axis in the peripubertal female rat exposed in utero and through lactatoin to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biol Reprod 56(6):1498-1502.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased ano-genital distance at 15 days of age; vagina partially occluded by vaginal thread; several morphological abnormalities in the urethra; increased cyctic hyperplasia of the endometrium; increased inflammatory lesions of the cervix

Subjects: Long Evans hooded rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: birth through adulthood

Reference [PubMed Link]
Gray LE, Kelce WR, Monosson E, Ostby JS, Birnbaum LS. 1995. Exposure to TCDD during development permanently alters reproductive function in male Long Evans rats and hamsters: Reduced ejaculated and epididymal sperm numbers and sex accessory gland weights in offspring with normal androgenic status. Toxicology & Applied Pharmacology 131(1):108-118.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased ano-genital distance at 16 days of age; increased age at vaginal opening; vagina partially occluded by vaginal thread; several morphological abnormalities in the urethra

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: birth through adulthood

Reference [PubMed Link]
Gray LE, Kelce WR, Monosson E, Ostby JS, Birnbaum LS. 1995. Exposure to TCDD during development permanently alters reproductive function in male Long Evans rats and hamsters: Reduced ejaculated and epididymal sperm numbers and sex accessory gland weights in offspring with normal androgenic status. Toxicology & Applied Pharmacology 131(1):108-118.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased ovarian weight

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: in late adulthood

Reference [PubMed Link]
Gray LE, Kelce WR, Monosson E, Ostby JS, Birnbaum LS. 1995. Exposure to TCDD during development permanently alters reproductive function in male Long Evans rats and hamsters: Reduced ejaculated and epididymal sperm numbers and sex accessory gland weights in offspring with normal androgenic status. Toxicology & Applied Pharmacology 131(1):108-118.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased age at vaginal opening at 0.8 μg/kg; decreased distance from urethral to vaginal opening and increased percent with vaginal thread and other urogenital abnormalities at 0.2 and 0.8 μg/kg; increased percent with cleft phallus at 0.8 μg/kg;

Subjects: Long Evans Hooded rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.05, 0.20 or 0.80 μg/kg bw

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: birth through adulthood

Reference [PubMed Link]
Gray LE Jr., Ostby JS. 1995. In utero 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters reproductive morphology and function in female rat offspring. Toxicology & Applied Pharmacology 133(2):285-294.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased estrogen receptor mRNA and DNA-binding activity in the uterus (not statistically tested)

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 21 days of age

Reference [PubMed Link]
Chaffin CL, Peterson RE, Hutz RJ. 1996. In utero and lactational exposure of female Holtzman rats to 2,3,7,8- tetrachlorodibenzo-p-dioxin: modulation of the estrogen signal. Biol Reprod 55(1):62-67.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased percentage of body weight attributed to the ovary; increased estrogen receptor mRNA in the ovary (using RNase protection assay -no statistical test)

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 21 days of age

Reference [PubMed Link]
Chaffin CL, Peterson RE, Hutz RJ. 1996. In utero and lactational exposure of female Holtzman rats to 2,3,7,8- tetrachlorodibenzo-p-dioxin: modulation of the estrogen signal. Biol Reprod 55(1):62-67.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased terminal end buds and decreased lobules II at 50 days of age; increased tumorigenesis in response to DMBA

Subjects: Sprague-Dawley rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg

Route of administration: delivered through gavage

Exposure duration: gestational day 15 (and cross-fostered after birth) – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 21 and 50 days of age

Reference [PubMed Link]
Brown NM, Manzolillo PA, Zhang JX, Wang J, Lamartiniere CA. 1998. Prenatal TCDD and predisposition to mammary cancer in the rat. Carcinogenesis 19(9):1623-1629.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased primary branches from the collecting duct, delayed migration of the epithelium through the fat pad and fewer terminal branches and alveolar buds

Subjects: Long-Evans rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: birth through 110 days of age

Reference [PubMed Link]
Fenton SE, Hamm JT, Birnbaum LS, Youngblood GL. 2002. Persistent abnormalities in the rat mammary gland following gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol Sci 67(1):63-74.
Study Results Study Details References

Results for Dioxin (TCDD)

Delayed vaginal opening, increased presence of vaginal threads

Subjects: Long-Evans rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: birth through 110 days of age

Reference [PubMed Link]
Fenton SE, Hamm JT, Birnbaum LS, Youngblood GL. 2002. Persistent abnormalities in the rat mammary gland following gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol Sci 67(1):63-74.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased percentage of terminal end buds and terminal ducts; decreased percentage of Lobules I and II; increased ERα mRNA and protein; differentiation of terminal ductal structures induced by 0.1 mg 17β-estradiol

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 11 weeks of age

Reference [PubMed Link]
Lewis BC, Hudgins S, Lewis A, Schorr K, Sommer R, Peterson RE, Flaws JA, Furth PA. 2001. In utero and lactational treatment with 2,3,7,8-tetrachlorodibenzo-p- dioxin impairs mammary gland differentiation but does not block the response to exogenous estrogen in the postpubertal female rat. Toxicol Sci 62(1):46-53.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased thickness of mesenchymal tissue between the caudal Mullerian ducts on gestational days 19 and 21; increased length of unfused Mullerian ducts on gestational days 20 and 21; numerous morphological differences (not statistically tested)

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: gestational days 18 through 21

Reference [PubMed Link]
Dienhart MK, Sommer RJ, Peterson RE, Hirshfield AN, Silbergeld EK. 2000. Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces developmental defects in the rat vagina. Toxicol Sci 56(1):141-149.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased frequency of cleft clitoris and vaginal thread

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: birth through adulthood

Reference [PubMed Link]
Flaws JA, Sommer RJ, Silbergeld EK, Peterson RE, Hirshfield AN. 1997. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces genital dysmorphogenesis in the female rat. Toxicology & Applied Pharmacology 147(2):351-362.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased separation of Mullerian Ducts in the caudal to cranial direction on gestational day 17; decreased length of unfused Mullerian Ducts on gestational day 17; increased separation of left and right Mullerian Ducts on gestational days 18 and 19; increased width of mesenchyme separating Mullarian Ducts on gestational days 18 and 19; decreased distance from initial vaginal separation to the appearance of separate left and right Mulleriain Ducts on gestational day 19; increased length of unfused Mullerian Ducts on gestational days 19, and 21; decreased epidermal growth factor receptor expression at gestational day 18; increased expression of TGFβ3 at gestational day 19; several effects on gene expression at gestational days 18 and 19

Subjects: Long Evans rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and delivered orally

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: gestational days 17 through 21

Reference [PubMed Link]
Hurst CH, Abbott B, Schmid JE, Birnbaum LS. 2002. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) disrupts early morphogenetic events that form the lower reproductive tract in female rat fetuses. Toxicol Sci 65(1):87-98.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased number of antral follicles less than 75,000 μm2, and greater than 100,000 μm2 and preantral follicles less than 50,000 μm2

Subjects: Holtzman rat

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 21 and 22 days of age

Reference [PubMed Link]
Heimler I, Trewin AL, Chaffin CL, Rawlins RG, Hutz RJ. 1998. Modulation of ovarian follicle maturation and effects on apoptotic cell death in Holtzman rats exposed to 2,3,7,8-tetrachlorodtbenzo-p-dioxin (TCDD) in utero and lactationally. Reprod Toxicol 12(1):69-73.
Study Results Study Details References

Results for Dioxin (TCDD)

Alterations in the expression of Nqo1, Cyp1b1, Cyp1a1, Ahrr and Hpgds at various time-points

Subjects: Sprague Dawley rats

Chemical: Dioxin (TCDD)

Low doses tested: 200.00 ng/kg bw

Route of administration: dissolved in sesame oil and administered orally

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: post-natal days 3, 5, 6, 10, 12 ,14, 25, 28, 40, 67, and 145

Reference [PubMed Link]
Magre S, Rebourcet D, Ishaq M, Wargnier R, Debard C, Meugnier E, Vidal H, Cohen-Tannoudji J, Le Magueresse-Battistoni B. 2012. Gender differences in transcriptional signature of developing rat testes and ovaries following embryonic exposure to 2,3,7,8-TCDD. PLoS One 7(7):e40306.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased anogenital distance on post-natal day 49 and decreased urethrovaginal distance on post-natal days 49, 70, and 91

Subjects: Wistar rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and administered orally

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: gestational day 20, post-natal days 21, 49, 56, 70, 91, 98, and 10 and 13 weeks of age

Reference [PubMed Link]
Takeda T, Matsumoto Y, Koga T, Mutoh J, Nishimura Y, Shimazoe T, Ishii Y, Ishida T, Yamada H. 2009. Maternal exposure to dioxin disrupts gonadotropin production in fetal rats and imprints defects in sexual behavior. J Pharmacol Exp Ther 329(3):1091-1099.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased StAR, Cyp11A1, Cyp19, 17β-HSD1, and 3β-HSD ovarian mRNA levels at gestational day 20; decreased ovarian weight on post-natal day 98

Subjects: Wistar rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw

Route of administration: dissolved in corn oil and administered orally

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: gestational day 20, post-natal days 21, 49, 56, 70, 91, 98, and 10 and 13 weeks of age

Reference [PubMed Link]
Takeda T, Matsumoto Y, Koga T, Mutoh J, Nishimura Y, Shimazoe T, Ishii Y, Ishida T, Yamada H. 2009. Maternal exposure to dioxin disrupts gonadotropin production in fetal rats and imprints defects in sexual behavior. J Pharmacol Exp Ther 329(3):1091-1099.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased number of days spent in estrus at 45 through 66 days of age; decreased ovulation rate at 125 through 166 days of age at 2.5 μg/kg; decreased number of large preovulatory antral follicles at 25 days of age at 2.5 μg/kg 48 hours after electrocardiogram (eCG) stimulation

Subjects: Sprague-Dawley rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 or 2.5 μg/kg bw

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: gestational day 15 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 23 through 165 days of age

Reference [PubMed Link]
Salisbury TB, Marcinkiewicz JL. 2002. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,4,7,8-pentachlorodibenzofuran reduces growth disrupts reproductive parameters in female rats. Biol Reprod 66(6):1621-1626.