Reproductive and developmental toxicity in F1 Sprague–Dawley male rats exposed to di-n-butyl phthalate in utero and during lactation and determination of its NOAEL

2004 ◽  
Vol 18 (5) ◽  
pp. 669-676 ◽  
Author(s):  
Yunhui Zhang ◽  
Xuezhi Jiang ◽  
Bingheng Chen
Keyword(s):  
Developmental Toxicity ◽  
In Utero ◽  
Male Rats ◽  
Sprague Dawley ◽  
Butyl Phthalate

scholarly journals In Utero Exposure to Di(n)butyl Phthalate Reduces Testicular Testosterone and Testes Size in a Dose-Dependent Manner in Harlan Sprague Dawley Fetal Rats.

2009 ◽  
Vol 81 (Suppl_1) ◽  
pp. 636-636
Author(s):  
Kembra L. Howdeshell ◽  
Johnathan Furr ◽  
Christy R. Lambright ◽  
Vickie Wilson ◽  
L. Earl Gray
Keyword(s):  
In Utero ◽  
In Utero Exposure ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Fetal Rats ◽  
Testes Size ◽  
Butyl Phthalate ◽  
Dose Dependent

scholarly journals Birthweight Depression in Male Rats Contiguous to Male Siblings in Utero Exposed to High Doses of 1,3-Butanediol during Organogenesis

1986 ◽  
Vol 5 (4) ◽  
pp. 189-196 ◽  
Author(s):  
R. F. Mankes ◽  
V. Renak ◽  
J. Fieseher ◽  
R. Lefevre
Keyword(s):  
Developmental Toxicity ◽  
In Utero ◽  
Cellular Damage ◽  
Male Rats ◽  
Body Weights ◽  
Fetal Repair ◽  
Dose Dependent Decrease ◽  
High Doses ◽  
Embryotoxic Effects ◽  
Dose Dependent

The embryotoxic effects of high doses of the narcotizing ethanol dimer 1,3-butanediol were evaluated in pregnant Long-Evans rats during the “critical period” of organogenesis. Butanediol was given by gavage at levels of 0,7060,4236, or 706 mg/kg per day (24,14.4, or 2.4% of the acute oral LD50 value for rats). Maternal sedation was observed at 7060 and 4236 mg/kg, but feed consumptions and maternal body weights were unaffected. Butanediol caused a significant, dose-dependent decrease in offspring birthweights. At the highest butanediol dose, birthweights were preferentially and significantly decreased in male pups not contiguous in utero to female siblings. Other group I1 offspring were not affected and did not differ significantly from controls. As butanediol was given prior to the period of greatest fetal growth and fetal sex steroidogenests, it is concluded that intra-uterine levels of female sex steroids (estradiol) enhance fetal repair of cellular damage (restitution ad integrum), whereas testosterone inhibits fetal repair or exacerbates previous embryonic damage by some unknown mechanism. Such interaction furthers the concept that intrauterine position affects the endpoints of developmental toxicity, as expressed at partuition.

scholarly journals Pharmacokinetics and pharmacodynamics of cyclopropylfentanyl in male rats

2021 ◽  
Author(s):  
Marianne Skov-Skov Bergh ◽  
Inger Lise Bogen ◽  
Nancy Garibay ◽  
Michael H. Baumann
Keyword(s):  
High Performance ◽  
Parent Drug ◽  
Rat Plasma ◽  
Male Rats ◽  
Sprague Dawley ◽  
Limit Of Quantification ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Blood Specimens

Abstract Background Illicitly manufactured fentanyl and its analogs are a major driving force behind the ongoing opioid crisis. Cyclopropylfentanyl is a fentanyl analog associated with many overdose deaths, but limited knowledge is available about its pharmacology. In the present study, we developed a bioanalytical method for the determination of cyclopropylfentanyl and its main metabolite cyclopropylnorfentanyl and evaluated pharmacokinetic-pharmacodynamic relationships in rats. Method An ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for determination of cyclopropylfentanyl and cyclopropylnorfentanyl in rat plasma. Male Sprague–Dawley rats fitted with jugular catheters and temperature transponders received cyclopropylfentanyl (30, 100, and 300 μg/kg) or saline subcutaneously. Blood specimens were withdrawn over an 8-h time period, along with measurements of pharmacodynamic endpoints. Results The analytical method was validated, and both analytes exhibited a low limit of quantification (15 pg/mL). Cyclopropylfentanyl caused dose-related increases in hot plate latency (ED50 = 48 µg/kg) and catalepsy (ED50 = 87 µg/kg) and produced long-lasting hypothermia at the highest dose. Plasma cyclopropylfentanyl rose rapidly in a dose-related fashion, reaching maximal concentration (Cmax) after 15–28 min, whereas metabolite Cmax occurred later at 45–90 min. Cyclopropylfentanyl Cmax values were similar to concentrations measured in non-fatal intoxications in humans; however, differences in parent drug: metabolite ratio indicated possible interspecies variance in metabolism. Conclusion Our study shows that cyclopropylfentanyl produces typical opioid-like effects in male rats. Cyclopropylfentanyl displays much greater analgesic potency when compared to morphine, suggesting that cyclopropylfentanyl poses increased overdose risk for unsuspecting users.

Functional and Morphological Reproductive Aspects in Male Rats Exposed to Di-n-Butyl Phthalate (DBP) in Utero and During Lactation

2010 ◽  
Vol 73 (13-14) ◽  
pp. 972-984 ◽  
Author(s):  
Wellerson R. Scarano ◽  
Fabíola C. Toledo ◽  
Marina T. Guerra ◽  
Patrícia F. F. Pinheiro ◽  
Raquel F. Domeniconi ◽  
...  
Keyword(s):  
In Utero ◽  
Male Rats ◽  
Butyl Phthalate

Molecular and toxicologic research in newborn hypospadiac male rats following in utero exposure to di-n-butyl phthalate (DBP)

Toxicology ◽  
2009 ◽  
Vol 260 (1-3) ◽  
pp. 120-125 ◽  
Author(s):  
Ying-Jian Zhu ◽  
Jun-Tao Jiang ◽  
Long Ma ◽  
Jie Zhang ◽  
Yan Hong ◽  
...  
Keyword(s):  
In Utero ◽  
Male Rats ◽  
In Utero Exposure ◽  
Butyl Phthalate

scholarly journals In Utero Exposure to Di(n-butyl)phthalate Induces Morphological and Biochemical Changes in Rats Postpuberty

2017 ◽  
Vol 45 (4) ◽  
pp. 526-535 ◽  
Author(s):  
Yuya Okayama ◽  
Shin Wakui ◽  
Michael F. Wempe ◽  
Mitsuru Sugiyama ◽  
Masaya Motohashi ◽  
...  
Keyword(s):  
Treatment Group ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cellular Proliferation ◽  
In Utero ◽  
Sprague Dawley ◽  
Morphological Alterations ◽  
Offspring Number ◽  
Testicular Weight ◽  
Butyl Phthalate

Pregnant Sprague-Dawley rats were orally administered di( n-butyl)phthalate (DBP; 100 mg/kg/day) on gestation days (GD) 12 to 21. We investigated the male offspring and probed morphological alterations in Sertoli cells at 7, 9, 14, and 17 weeks of age. Parameters assessed in this study included offspring number, sex ratios, body weights, testis weights, seminiferous tubule (ST) profile numbers and diameters, number of vimentin-labeled Sertoli cells, and both testosterone and follicle-stimulating hormone (FSH) levels. Testicular weight/body weight ratios and the numbers and diameters of ST in maximum transverse testicular sections were statistically similar at weeks 7 and 9; however, at weeks 14 and 17, they were statistically different and displayed higher BrdU-positive Sertoli cells/Sertoli cell ratios in the DBP treatment group. Noteworthily, the serum FSH levels were higher and testicular testosterone levels were lower in the DBP treatment group. To our knowledge, the present study is the first to report that in utero DBP exposure significantly increased Sertoli cell numbers and their cellular proliferation from postpuberty to adulthood, with a significant decrease in testicular testosterone and an increase in FSH.

scholarly journals Hypothyroidism protects di(n-butyl) phthalate-induced reproductive organs damage in Sprague-Dawley male rats

2008 ◽  
Vol 33 (3) ◽  
pp. 299-306 ◽  
Author(s):  
Ena Lee ◽  
Hee Jin Kim ◽  
Ji Young Im ◽  
Jeonga Kim ◽  
Hyeyoung Park ◽  
...  
Keyword(s):  
Reproductive Organs ◽  
Male Rats ◽  
Sprague Dawley ◽  
Butyl Phthalate

scholarly journals Male Sprague-Dawley Rats Exposed to In Utero Di(n-butyl) Phthalate

2013 ◽  
Vol 41 (7) ◽  
pp. 984-991 ◽  
Author(s):  
Masaru Shirai ◽  
Shin Wakui ◽  
Michael F. Wempe ◽  
Tomoko Mutou ◽  
Noriko Oyama ◽  
...  
Keyword(s):  
In Utero ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Butyl Phthalate
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