Enhanced one-generation reproductive toxicity study in rats for detecting endocrine-disrupting effects of chemicals

2003 ◽  
Vol 75 (11-12) ◽  
pp. 2497-2501 ◽  
Author(s):  
H. Aoyama ◽  
K. Suzuki
Keyword(s):  
Reproductive Toxicity ◽  
Toxicity Study ◽  
Test Substance ◽  
Lactation Period ◽  
Pilot Studies ◽  
Estrogenic Effects ◽  
Endocrine Disrupting ◽  
Dose Effects ◽  
Estrous Cyclicity ◽  
Estrogenic Chemicals

An enhanced one-generation reproductive toxicity study in rats without adjusting a litter size during the lactation period is proposed as a rapid and reliable bioassay for providing the data concerning adverse and/or low-dose effects of suspected endocrine disruptors. In this study, pregnant females are treated with the test substance from gestation day 0 through lactation day 21, in principle. F1 offspring from one-half of the litters in each dose group are killed and necropsied at weaning, while those from the remaining litters are examined for sexual maturation, estrous cyclicity, and/or sperm production. A series of pilot studies with ethynylestradiol as a reference chemical have suggested that the exposure of estrogenic chemicals during the early gestation period is critical for detecting effects on fertilization and/or implantation of eggs and survival of implants, and that expression of some genes including AR in the prostate and IGF-1 in the uterus of F1 offspring may be sensitive markers for monitoring potential estrogenic effects of the test compound.

Effects of endocrine disruptor furan on reproductive physiology of Sprague Dawley rats: An F1 Extended One-Generation Reproductive Toxicity Study (EOGRTS)

2020 ◽  
Vol 39 (8) ◽  
pp. 1079-1094 ◽  
Author(s):  
H Rehman ◽  
S Jahan ◽  
I Ullah ◽  
P-O Thörnqvist ◽  
M Jabbar ◽  
...  
Keyword(s):  
Reproductive Toxicity ◽  
Head Tilt ◽  
Treated Group ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Estrous Cyclicity ◽  
F1 Generation

The present study investigated the reproductive toxicity of furan in an Extended One-Generation Reproductive Toxicity Study in rats. Sprague Dawley F0 weaning rats (30 per sex per group) were exposed to furan orally at 0, 1, 2.5, 5, and 10 mg kg−1 for 10 weeks (males) and 2 weeks (females) and then mated. Results of F0 indicated that in the furan-treated groups (5 mg kg−1 and 10 mg kg−1), body weight (bw) gain decreased during prebreed and gestational period while increased during lactation periods. F0 animals prebreeding exposure resulted in head tilt and foot splay at 10 mg kg−1. Number of live pups at birth were decreased ( p < 0.001) at 10 mg kg−1. At postnatal day (PND) 70, a significant ( p = 0.03) decrease in testosterone levels of male rats and estrogen levels of female rats ( p = 0.05) was observed in 10 mg kg−1 furan-treated group in F1 generation. Luteinizing hormone, follicle-stimulating hormone, and progesterone levels were also reduced, but their reduction was not statistically significant in all groups. In higher dose furan group (10 mg kg−1), testicular and ovarian weights were reduced in F1 generation at PND 70, with decreased daily sperm production ( p = 0.01) and disturbed estrous cyclicity ( p < 0.01). Some histopathological changes were also observed in testis and ovaries in groups whose parents were previously exposed to 10 mg kg−1 bw of furan group. Based on the above results, it is suggested that exposure to food-based contaminant furan induced remarkable changes in the F0 (parental stage) and F1 (offspring, pubertal, and adult stage) generations of Sprague Dawley rats.

scholarly journals Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats

Reproduction ◽  
2014 ◽  
Vol 147 (4) ◽  
pp. 489-501 ◽  
Author(s):  
Marta Axelstad ◽  
Sofie Christiansen ◽  
Julie Boberg ◽  
Martin Scholze ◽  
Pernille Rosenskjold Jacobsen ◽  
...  
Keyword(s):  
Human Exposure ◽  
Endocrine Disrupting Chemicals ◽  
Reproductive Toxicity ◽  
Safety Margin ◽  
Levator Ani ◽  
Ventral Prostate ◽  
High Dose ◽  
Reproductive Effects ◽  
Endocrine Disrupting ◽  
Estrogenic Chemicals

Reproductive toxicity was investigated in rats after developmental exposure to a mixture of 13 endocrine-disrupting contaminants, including pesticides, plastic and cosmetic ingredients, and paracetamol. The mixture was composed on the basis of information about high-end human exposures, and the dose levels reflecting 100, 200, and 450 times this exposure were tested. The compounds were also grouped according to their estrogenicity or anti-androgenicity, and their joint effects were tested at two different doses, with each group reflecting 200 or 450 times human exposure. In addition, a single paracetamol dose was tested (350 mg/kg per day). All exposures and a vehicle were administered by oral gavage to time-mated Wistar dams rats throughout gestation and lactation, and their offspring were assessed for reproductive effects at birth and in prepuberty. The mixture doses, which included the anti-androgenic compounds, affected the male offspring by causing decreased anogenital distance, increased nipple retention (NR), and reduced ventral prostate weights, at both medium and high doses. In addition, the weights of the levator ani/bulbocavernosus muscle (LABC) were decreased at the high dose of anti-androgen mixture. No effects were seen after exposure to the estrogenic chemicals alone, whereas males exposed solely to paracetamol showed decreased LABC weights and increased NR. Thus adverse reproductive effects were observed at mixtures reflecting 200 times high-end human exposure, which is relatively close to the safety margin covered by the regulatory uncertainty factor of 100. This suggests that highly exposed human population groups may not be sufficiently protected against mixtures of endocrine-disrupting chemicals.

103. Multi-Generation Reproductive Toxicity Study of Implanted Depleted Uranium in Rats

2004 ◽  
Author(s):  
D. Arfsten ◽  
A. Thitoff ◽  
E. Johnson ◽  
A. Jung ◽  
W. Jederberg ◽  
...  
Keyword(s):  
Reproductive Toxicity ◽  
Depleted Uranium ◽  
Toxicity Study

scholarly journals Palmitoylethanolamide: Prenatal Developmental Toxicity Study in Rats

2021 ◽  
pp. 109158182098607
Author(s):  
Narendra S. Deshmukh ◽  
Shailesh Gumaste ◽  
Silma Subah ◽  
Nathasha Omal Bogoda
Keyword(s):  
Body Weight ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Toxicity Study ◽  
High Dose ◽  
Pregnant Rats ◽  
Human Dose ◽  
Adverse Effect Level ◽  
Female Wistar Rats ◽  
Effect Level

Palmitoylethanolamide (PEA) is an endogenous ethanolamine playing a protective and homeodynamic role in animals and plants. Prenatal developmental toxicity of PEA was tested following oral administration to pregnant female Wistar rats, from days 0 to 19 of gestation, at dosage of 250, 500, or 1,000 mg/kg body weight, according to Organisation for Economic Co-operation and Development Test Guideline No. 414. On gestation day 20, cesarean sections were performed on the dams, followed by examination of their ovaries and uterine contents. The fetuses were further examined for external, visceral, and skeletal abnormalities. Palmitoylethanolamide did not cause any alterations at any of the given dosages in the measured maternal parameters of systemic toxicity (body weight, food consumption, survival, thyroid functions, organ weight, histopathology), reproductive toxicity (preimplantation and postimplantation losses, uterus weight, number of live/dead implants and early/late resorptions, litter size and weights, number of fetuses, their sex ratio), and fetal external, visceral, or skeletal observations. Any alterations that were recorded were “normal variations” or “minor anomalies,” which were unrelated to treatment with PEA. Under the condition of this prenatal study, the no-observed-adverse-effect level of PEA for maternal toxicity, embryotoxicity, fetotoxicity, and teratogenicity in rats was found to be >1,000 mg/kg body weight/d. It indicates that PEA is well tolerated by and is safe to pregnant rats even at a high dose of 1,000 mg/kg body weight/d, equivalent to a human dose of greater than 9.7 g/d. This prenatal developmental toxicity study contributes greatly in building a robust safety profile for PEA.

A Two-Generation Reproductive Toxicity Study of Lanthanum Nitrate in SD Rats

2021 ◽  
Author(s):  
Lang Yan ◽  
Fangyuan Gao ◽  
Wenjing Shi ◽  
Bijiang Geng ◽  
Jiqianzhu Zhang ◽  
...  
Keyword(s):  
Reproductive Toxicity ◽  
Lanthanum Nitrate ◽  
Toxicity Study ◽  
Sd Rats

One-generation reproduction toxicity study of Dithane M-45 (mancozeb) and lead acetate

2002 ◽  
Vol 50 (3) ◽  
pp. 365-371 ◽  
Author(s):  
L. Várnagy ◽  
P. Budai ◽  
E. Molnár ◽  
Keyword(s):  
Body Weight ◽  
Lead Acetate ◽  
Clinical Symptoms ◽  
Reproductive Toxicity ◽  
The Body ◽  
High Dose ◽  
Lactation Period ◽  
Treatment Groups ◽  
Body Weight Increase ◽  
Dose Levels

The reproductive toxicity of lead acetate and of a fungicide formulation (Dithane M-45) containing 80% mancozeb was studied on rats. Lead acetate was applied in the feed in the following dose groups: control, 1,000, 5,000 and 10,000 mg/kg of diet. The three treatment groups received, in addition to the above doses of lead acetate, 4,500 mg/kg Dithane M-45 in the diet. The method was based on the OECD Guideline for Testing of Chemicals No. 415 (1981). Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals decreased significantly before the pregnancy period. This tendency was also seen in males after the combination treatment. At the two high dose levels a remarkable body weight increase was seen in the female animals during the lactation period. As a result of treatment, decreased body weight of offspring was measured during the lactation period. No gross pathological changes were seen. Histological examination showed general tubulonephrosis in the experimental animals. It can be established that the administration of Dithane M-45 did not enhance the reproductive toxicity of lead acetate.

Significance, Reliability, and Interpretation of Developmental and Reproductive Toxicity Study Findings

2005 ◽  
pp. 329-424 ◽  
Author(s):  
Mark Nemec ◽  
Lewis Kaufman ◽  
Donald Stump ◽  
Pia Lindström ◽  
Bennett Varsho ◽  
...  
Keyword(s):  
Reproductive Toxicity ◽  
Toxicity Study

A retrospective analysis of the two-generation reproductive toxicity study

2007 ◽  
Vol 172 ◽  
pp. S16
Author(s):  
Gemma Janer ◽  
Aldert H. Piersma ◽  
Betty C. Hakkert ◽  
Theo Vermeire ◽  
Wout Slob
Keyword(s):  
Retrospective Analysis ◽  
Reproductive Toxicity ◽  
Toxicity Study
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