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)

Varied effects on CYP1A1 mRNA, AhR and ARNT.

Subjects: Human embryonic craniofacial tissues

Chemical: Dioxin (TCDD)

Low doses tested: 0.1, 1.0, or 10.0 nM

Route of administration: in vitro culture

Exposure duration: gestational day 42 to 54 (human) – 2-48 hours in vitro (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 4 through 48 hours culture

Reference [PubMed Link]
Abbott BD, Held GA, Wood CR, Buckalew AR, Brown JG, Schmid J. 1999. AhR, ARNT, and CYP1A1 mRNA quantitation in cultured human embryonic palates exposed to TCDD and comparison with mouse palate in vivo and in culture. Toxicol Sci 47(1):62-75.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased inhibition of degeneration of medial peridermal cell death in rat palatal shelves at 0.001 and 0.01 μM

Subjects: F344 rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.00005, 0.0001, 0.001, or 0.01 μM

Route of administration: placed in 5 percent fetal bovine serum and 0.1 percent DMSO

Exposure duration: gestational day 14 – gestational day 16 or 17 (comparable to human prenatal development from approximately day 1 of week 6 to beyond birth)

Age of measurement: 48 - 72 hours

Reference [PubMed Link]
Abbott BD, Birnbaum LS. 1990. Rat embryonic palatal shelves respond to TCDD in organ-culture. Toxicol Appl Pharmacol 103(3):441-451.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased serum estradiol (E2) concentrations at all time points across the estrous cycle in a dose-dependent manner for doses as low as 0.005 μg/kg/week

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)

Increased procrustes distance (difference in molar shape) for male b/b genotype, and for female b/b and d/d genotypes at 1.0 μg/kg; increased procrustes distance (differences in mandible shape) for male b/b genotype at 0.01 and 1.0 μg/kg; (b/b and d/d genotypes differ only in AhR locus)

Subjects: C57BL/6 mice

Chemical: Dioxin (TCDD)

Low doses tested: 0.01, 0.1, or 1.0 μg/kg bw

Route of administration: dissolved in corn oil and delivered orally

Exposure duration: gestational day 13 – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 70 days of age

Reference [PubMed Link]
Keller JM, Huang JC, Huet-Hudson Y, Leamy LJ. 2007. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on molar and mandible traits in congenic mice: A test of the role of the Ahr locus. Toxicology 242(1-3):52-62.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased FSHβ mRNA at 21 days of age

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 pituitary weight at 0.8 μg/kg at 49 days of age and at 0.2 and 0.8 μg/kg at 63 days of age

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, Kelce WR. 1997. A dose-response analysis of the reproductive effects of a single gestational dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male Long Evans Hooded rat offspring. Toxicology & Applied Pharmacology 146(1):11-20.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased follicle-stimulating hormone concentrations in juveniles (32 days) at lowest and two higher doses.

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.064, 0.16, 0.40 or 1.0 μg/kg bw

Route of administration: dissolved in corn oil and fed 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: 32, 49, 63 and 120 days of age

Reference [PubMed Link]
Mably TA, Bjerke DL, Moore RW, Gendron-Fitzpatrick A, Peterson RE. 1992. In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3. Effects on spermatogenesis and reproductive capability. Toxicology & Applied Pharmacology 114(1):118-126.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased growth hormone-releasing hormone mRNA; decreased somatostatin mRNA and galanin mRNA

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
Chaffin CL, Brogan RS, Peterson RE, Hutz RJ, Wehrenberg WB. 1996. Modulation of growth axis gene expression by in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the weanling Holtzman rat. Endocr J 5:129-134.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased serum growth hormone

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
Chaffin CL, Brogan RS, Peterson RE, Hutz RJ, Wehrenberg WB. 1996. Modulation of growth axis gene expression by in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the weanling Holtzman rat. Endocr J 5:129-134.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased estrogen receptor mRNA and decreased estrogen receptor DNA-binding activity (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)

Decreased estrogen receptor mRNA (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)

Decreased serum estrogen concentrations

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)

Decreased core body temperature

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: in adulthood

Reference [PubMed Link]
Gordon CJ, Gray LE, Monteiro-Riviere NA, Miller DB. 1995. Temperature regulation and metabolism in rats exposed perinatally to dioxin - Permanent change in regulated body temperature. Toxicology & Applied Pharmacology 133(1):172-176.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased plasma luteinizing hormone at two highest doses in castrated males given progesterone and estradiol benzoate

Subjects: Not specified rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.064, 0.16, 0.40 or 1.0 μg/kg bw

Route of administration: 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: 60, 75 and 115 days of age

Reference
Peterson RE, Mably TA, Moore RW, Goy RW. 1992. In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin: Effects on sexual behavior and the regulation of luteinizing hormone secretion in adulthood. Chemosphere 25(1-2):157-160.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased sex ratio of aromatase activity on gestational day 20 and at 2 days of age

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.8 or 1.6 μg/kg

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 16 and 20 and at 2 days of age

Reference
Ikeda M, Inukai N, Mitsui T, Sone H, Yonemoto J, Tohyama C, Tomita T. 2002. Changes in fetal brain aromatase following in utero 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in rats. Environmental Toxicology & Pharmacology 11(1):1-7.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased GAD67 mRNA levels in the rPOA/AVPV region in females only; decreased GAD67 mRNA levels in the caudal MPN in males only

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg

Route of administration: delivered orally in a treated wafer

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: 3 days of age

Reference [PubMed Link]
Hays LE, Carpenter CD, Petersen SL. 2002. Evidence that GABAergic neurons in the preoptic area of the brain are targets of 2,3,7,8-tetrachloro-p-dioxin during development. Environ Health Perspect 110 (suppl 3):369-376.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased nocturnal core body temperature and increased diurnal core temperature at various ages; hypothermic effects

Subjects: Long-Evans rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg

Route of administration: 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: 3 months of age through adulthood

Reference [PubMed Link]
Gordon CJ, Miller DB. 1998. Thermoregulation in rats exposed perinatally to dioxin - core temperature stability to altered ambient temperature, behavioral thermoregulation, and febrile response to lipopolysaccharide. Journal of Toxicology & Environmental Health. Part A 54(8):647-662.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased T4 concentrations on post-natal day 21 (although not significant among females at 200 μg/kg); increased T4 at 800 μg/kg at 49 days among males only; increased T3 concentration at 800 μg/kg at 21 days among females only; increased TSH at 800 μg/kg at both time points.

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.2 or 0.8 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, 21 and 49 days of age

Reference [PubMed Link]
Nishimura N, Yonemoto J, Miyabara Y, Sato M, Tohyama C. 2003. Rat thyroid hyperplasia induced by gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Endocrinology 144(5):2075-2083.
Study Results Study Details References

Results for Dioxin (TCDD)

At post-natal day 49: increased ratio of parenchymal area to follicular area at 800 μg/kg compared to controls, and in males compared to females; increased ratio of PCNA-positive cells to total number of follicular cells at 800 μg/kg compared to controls, and in males compared to females

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.2 or 0.8 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, 21 and 49 days of age

Reference [PubMed Link]
Nishimura N, Yonemoto J, Miyabara Y, Sato M, Tohyama C. 2003. Rat thyroid hyperplasia induced by gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Endocrinology 144(5):2075-2083.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased expression of of cytochrome P450 17 (CYP17) in fetal adrenal glands for both sexes

Subjects: Wistar 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 day 20

Reference [PubMed Link]
Mutoh J, Taketoh J, Okamura K, Kagawa T, Ishida T, Ishii Y, Yamada H. 2006. Fetal pituitary gonadotropin as an initial target of dioxin in its impairment of cholesterol transportation and steroidogenesis in rats. Endocrinology 147(2):927-936.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased expression of β-subunit of leutenizing hormone mRNA in pituitary of fetal brain

Subjects: Wistar 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 day 20

Reference [PubMed Link]
Mutoh J, Taketoh J, Okamura K, Kagawa T, Ishida T, Ishii Y, Yamada H. 2006. Fetal pituitary gonadotropin as an initial target of dioxin in its impairment of cholesterol transportation and steroidogenesis in rats. Endocrinology 147(2):927-936.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased serum leutenizing hormone

Subjects: Wistar 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 day 20

Reference [PubMed Link]
Mutoh J, Taketoh J, Okamura K, Kagawa T, Ishida T, Ishii Y, Yamada H. 2006. Fetal pituitary gonadotropin as an initial target of dioxin in its impairment of cholesterol transportation and steroidogenesis in rats. Endocrinology 147(2):927-936.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased serum estradiol

Subjects: Holtzman 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 18 through 21

Reference [PubMed Link]
Timms BG, Peterson RE, vom Saal FS. 2002. 2,3,7,8-tetrachlorodibenzo-p-dioxin interacts with endogenous estradiol to disrupt prostate gland morphogenesis in male rat fetuses. Toxicol Sci 67(2):264-274.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased inhibition of degeneration of medial peridermal cell death in rat palatal shelves at 0.001 and 0.01 μM

Subjects: F344 rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.00005, 0.0001, 0.001, or 0.01 μM

Route of administration: placed in 5 percent fetal bovine serum and 0.1 percent DMSO

Exposure duration: gestational day 15 – gestational day 17 or 18 (comparable to human prenatal development from approximately day 1 of week 6 to beyond birth)

Age of measurement: 48 - 72 hours

Reference [PubMed Link]
Abbott BD, Birnbaum LS. 1990. Rat embryonic palatal shelves respond to TCDD in organ-culture. Toxicol Appl Pharmacol 103(3):441-451.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased plasma testosterone concentrations at 63 days of age by in utero and lactational exposure

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg

Route of administration: dissolved in corn oil and delivered orally

Exposure duration: gestational day 15 (and cross-fostered at birth) – 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 140 days of age

Reference [PubMed Link]
Bjerke DL, Peterson RE. 1994. Reproductive toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male-rats - different effects of in utero versus lactational exposure. Toxicol Appl Pharmacol 127(2):241-249.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased total serum androgen at 45 days of age at 1.0 μg/kg; increased total serum androgen at 120 days of age at 1.0 μg/kg; decreased mean testosterone and dihydrotestosterone (DHT) at 1.0 μg/kg

Subjects: Sprague-Dawley rat

Chemical: Dioxin (TCDD)

Low doses tested: 0.2, or 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: 15 through 120 days of age

Reference [PubMed Link]
Cooke GM, Price CA, Oko RJ. 1998. Effects of in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on serum androgens and steroidogenic enzyme activities in the male rat reproductive tract. J Steroid Biochem Mol Biol 67(4):347-354.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased serum estrogen at 21 days of age

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)

Decreased eruption of 3rd lower molars in line A females at 35 days of age at 0.3 and 1.0 μg/kg; decreased mesiodistal length (MDL) of lower 3rd molars at various doses and strains, with similar but fewer effects for lower 1st and 2nd molars

Subjects: A, B, and C lines of Han/Wistar and Long/Evans crossing rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.03, 0.1, 0.3 or 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: 35 and 70 days of age

Reference [PubMed Link]
Kattainen H, Tuukkanen J, Simanainen U, Tuomisto JT, Kovero O, Lukinmaa PL, Alaluusua S, Tuomisto J, Viluksela M. 2001. In utero/lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure impairs molar tooth development in rats. Toxicology & Applied Pharmacology 174(3):216-224.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased plasma luteinizing hormone (LH) concentrations in male rats 140 days after castration and 36-45 hours after estradiol and progesterone injections at 0.4 and 1.0 μg/kg

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.064, 0.16, 0.40, or 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: 60 through 270 days of age

Reference [PubMed Link]
Mably TA, Moore RW, Goy RW, Peterson RE. 1992. In utero and lactational exposure of male-rats to 2,3,7,8-tetrachlorodibenzo-para-dioxin. 2. Effects on sexual-behavior and the regulation of luteinizing-hormone secretion in adulthood. Toxicol Appl Pharmacol 114(1):108-117.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased plasma luteinizing hormone (LH) level for males at 32 days of age at 1.0 μg/kg

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.064, 0.16, 0.40, or 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: birth through sexual maturation

Reference [PubMed Link]
Mably TA, Moore RW, Peterson RE. 1992. In utero and lactational exposure of male-rats to 2,3,7,8-tetrachlorodibenzo-para-dioxin. 1. Effects on androgenic status. Toxicol Appl Pharmacol 114(1):97-107.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased plasma testosterone levels in males at gestational days 18 through 21

Subjects: Holtzman 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 day 18 through 5 days of age

Reference [PubMed Link]
Mably TA, Moore RW, Peterson RE. 1992. In utero and lactational exposure of male-rats to 2,3,7,8-tetrachlorodibenzo-para-dioxin. 1. Effects on androgenic status. Toxicol Appl Pharmacol 114(1):97-107.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased serum estradiol (E2) levels 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.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased Cyp 1a1 levels and alterations in the hypothalamic content of ATP and TCA cycle components

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

Reference [PubMed Link]
Koga T, Ishida T, Takeda T, Ishii Y, Uchi H, Tsukimori K, Yamamoto M, Himeno M, Furue M, Yamada H. 2012. Restoration of dioxin-induced damage to fetal steroidogenesis and gonadotropin formation by maternal co-treatment with alpha-lipoic acid. PLoS One 7(7):e40322.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased number of offspring with all third molars developed for animals exposed in utero; decreased mesiodistal length of existing lower molars for both lactational and in utero exposure; increased incidence of erupted lower incisors at 9 through 11 days of age for both lactational and in utero exposure

Subjects: Line C (highly sensitive to TCDD) 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 (and cross-fostered at birth) – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 40 days of age

Reference [PubMed Link]
Miettinen HM, Alaluusua S, Tuomisto J, Viluksela M. 2002. Effect of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on rat molar development: The role of exposure time. Toxicol Appl Pharmacol 184(1):57-66.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased bone mineral density, cross-sectional area of cortex, periosteal circumference, endosteal circumference, and polar cross-sectional moment of inertia in line C rats at 1.0 μg/kg; decreased breaking force and stiffness of tibia and femoral neck in line C females at 35 days of age at 1.0 μg/kg

Subjects: Line A (least sensitive to TCDD), B, and C (most sensitive) rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.03, 0.1, 0.3, or 1.0 μg/kg bw; dose response study

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: birth through 35 days of age

Reference [PubMed Link]
Miettinen HM, Pulkkinen P, Jamsa T, Koistinen J, Simanainen U, Tuomisto J, Tuukkanen J, Viluksela M. 2005. Effects of in utero and lactational TCDD exposure on bone development in differentially sensitive rat lines. Toxicol Sci 85(2):1003-1012.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased stiffness of femoral neck in line C females; decreased length of femur and periosteal circumference (PERI) for line C males exposed in utero; decreased length of tibia and femur and endosteal circumference (ENDO) for line C males exposed lactationally; decreased PERI and polar cross-sectional moment of inertia (PMI) of tibia for line C females exposed in utero; decreased PERI, and PMI of tibia and decreased PERI, ENDO, and PMI of femur for line C females exposed lactationally

Subjects: Line A (least sensitive to TCDD), B, and C (most sensitive) 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 (and cross-fostered at birth) – single dose (comparable to human prenatal development from approximately day 1 of week 6 to day 1 of week 7)

Age of measurement: 40 days of age

Reference [PubMed Link]
Miettinen HM, Pulkkinen P, Jamsa T, Koistinen J, Simanainen U, Tuomisto J, Tuukkanen J, Viluksela M. 2005. Effects of in utero and lactational TCDD exposure on bone development in differentially sensitive rat lines. Toxicol Sci 85(2):1003-1012.
Study Results Study Details References

Results for Dioxin (TCDD)

Increased cariogenic lesions in tooth enamel at 0.03 and 1.0 μg/kg; increased percentage missing all lower third molars and one or two upper third molars at 1.0 μg/kg; increased number of caries for males and females at all doses in the presence of sugar-rich diet and S. Mutans; decreased weight percentage of magnesium oxide in tooth enamel at 1.0 μg/kg

Subjects: Line C (highly sensitive to TCDD) rats

Chemical: Dioxin (TCDD)

Low doses tested: 0.03, 0.1, 0.3, or 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: 77 days of age

Reference [PubMed Link]
Miettinen HM, Sorvari R, Alaluusua S, Murtomaa M, Tuukkanen J, Viluksela M. 2006. The effect of perinatal TCDD exposure on caries susceptibility in rats. Toxicol Sci 91(2):568-575.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased serum total thyroxin (TT4) in males and females exposed via lactation only and via both in utero and lactation; decreased free thyroxin in males exposed via lactation and females via both in utero and lactation; increased serum thyroid stimulating hormone (TSH) in males exposed via lactation and via both in utero and lactation

Subjects: Holtzman rats

Chemical: Dioxin (TCDD)

Low doses tested: 1.0 μg/kg bw; cross-fostered

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: 21 days of age

Reference [PubMed Link]
Nishimura N, Yonemoto J, Nishimura H, Ikushiro S, Tohyama C. 2005. Disruption of thyroid hormone homeostasis at weaning of holtzman rats by lactational but not in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci 85(1):607-614.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased KCl-evoked GnRH release with increased GnRH content. Alterations in somal profiles such that TCDD increased smooth and decreased lightly thorny profiles in the lateral preoptic area with decreased heavily thorny profiles in the septal region. Somal area was decreased in the lateral preoptic area.

Subjects: Sprague Dawley rats

Chemical: Dioxin (TCDD)

Low doses tested: 5.0 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: post-natal day 35, 60 or 90

Reference [PubMed Link]
Clements RJ, Lawrence RC, Blank JL. 2009. Effects of intrauterine 2,3,7,8-tetrachlorodibenzo-p-dioxin on the development and function of the gonadotrophin releasing hormone neuronal system in the male rat. Reprod Toxicol 28(1):38-45.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased LHβ and FSHβ mRNA with increased Cyp1a1 levels

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

Reference [PubMed Link]
Koga T, Ishida T, Takeda T, Ishii Y, Uchi H, Tsukimori K, Yamamoto M, Himeno M, Furue M, Yamada H. 2012. Restoration of dioxin-induced damage to fetal steroidogenesis and gonadotropin formation by maternal co-treatment with alpha-lipoic acid. PLoS One 7(7):e40322.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased serum testosterone and LH levels

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

Reference [PubMed Link]
Koga T, Ishida T, Takeda T, Ishii Y, Uchi H, Tsukimori K, Yamamoto M, Himeno M, Furue M, Yamada H. 2012. Restoration of dioxin-induced damage to fetal steroidogenesis and gonadotropin formation by maternal co-treatment with alpha-lipoic acid. PLoS One 7(7):e40322.
Study Results Study Details References

Results for Dioxin (TCDD)

Alterations in Ahrr, Cyp1a1, Cyp1b1, and Nqo1 on post-natal days 6 and 14 in females, and Gzmf, Art2b, and Fgf13 on post-natal days 3 and 12 in females.

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 pituitary mRNA levels of LHβ and FSHβ on gestational day 20.

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 and post-natal day 7

Reference [PubMed Link]
Matsumoto Y, Ishida T, Takeda T, Koga T, Fujii M, Ishii Y, Fujimura Y, Miura D, Wariishi H, Yamada H. 2010. Maternal exposure to dioxin reduces hypothalamic but not pituitary metabolome in fetal rats: a possible mechanism for a fetus-specific reduction in steroidogenesis. J Toxicol Sci 35(3):365-373.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased mRNA levels of LHβ on gestational days 19, 20, 21 and post-natal day 0, decreased FSHβ on gestational days 20 and 21 and post-natal day 0, decreased αGSU on gestational day 21. Decreased GnRH receptor mRNA levels on gestational day 20 and 21 and post-natal day 0. Alterations in mRNA expression of various HDAC mRNAs at various time points in males. Reduced aceylation of histone H3 and H4 around LHβ promoter.

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 days 18, 19, 20 and 21 post-natal days 0, 2, 4 and 7

Reference [PubMed Link]
Takeda T, Fujii M, Taura J, Ishii Y, Yamada H. 2012. Dioxin silences gonadotropin expression in perinatal pups by inducing histone deacetylases: a new insight into the mechanism for the imprinting of sexual immaturity by dioxin. J Biol Chem 287(22):18440-18450.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased serum LH on gestational days 20 and 21 and post-natal day 0. Decreased serum FSH on gestational days 20 and 21 and post-natal days 0 and 2.

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 days 18, 19, 20 and 21 post-natal days 0, 2, 4 and 7

Reference [PubMed Link]
Takeda T, Fujii M, Taura J, Ishii Y, Yamada H. 2012. Dioxin silences gonadotropin expression in perinatal pups by inducing histone deacetylases: a new insight into the mechanism for the imprinting of sexual immaturity by dioxin. J Biol Chem 287(22):18440-18450.
Study Results Study Details References

Results for Dioxin (TCDD)

Decreased LHβ and FSHβ mRNA in males and females on gestational day 20 with decreased αSub mRNA levels in males only.

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 serum LH and FSH levels in males and females at gestational day 20

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.