scholarly journals Reproductive toxicity of triazole fungicides cyproconazole and epoxiconazole when exposed to male and female wistar rats during gametogenesis

2021 ◽  
Vol 54 (1) ◽  
pp. 52-61
Author(s):  
NR Shepelskaya ◽  
YaV Kolyanchuk
Keyword(s):  
Body Weight ◽  
Reproductive Toxicity ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Corpora Lutea ◽  
Disruptive Effect ◽  
Male And Female ◽  
Two Samples ◽  
Adverse Effect Level

Aim. Studying the effect of generic pesticides cyproconazole (98 %) and two samples of epoxiconazole (epoxiconazole 1 — 95,75 % and epoxiconazole 2 — 98,7 %) on the reproductive system of male and female Wistar Han rats at the level of the organism when exposed during gametogenesis, identification and characterization of their hazard, as well as assessment of the risk of reproductive toxicity of these compounds. Materials and Methods. The test samples were administered daily (5 days a week) by oral gavage at doses of 0.2 and 2.0 mg/kg for cyproconazole and 0.5 and 2.0 mg/kg for epoxiconazoles during 11 weeks for males, and 10 weeks for females. Also, there were kept intact males and females, intended for crossover mating with experimental animals. After the end of the exposure, functional indicators of the state of the gonads and the ability of animals to reproduce offspring were studied. The duration and the frequency of each stage of the estrous cycle in female rats and the number of motile sperm, the total amount of sperm and the number of abnormal forms of germ cells of the male rats were studied. The reproductive function state in females was evaluated on day 20th of pregnancy. Thereby the number of corpora lutea in the ovaries, number of alive, dead and resorbed foetuses and embryos, the foetus weight, total weight of litters were registered. The studies were carried out in accordance with the recommendations of the Bioethics Commission and the Centre’s standard operating procedures, developed in accordance with the recommendations and requirements of Good Laboratory Practice (GLP). Conclusions. Test substances at a maximum dose of 2.0 mg/kg of body weight have reproductive toxicity and endocrine-disruptive effect, exerting a significant antiandrogenic effect on males and antiestrogenic effect on female rats. No-observed-adverse-effect-level (NOАEL) for gonadal and reproductive toxicity for male and female Wistar Han rats were established. They are 0.2 mg/kg body weight for cyproconazole and 0.5 mg/kg body weight for epoxiconazole. Key Words: azole fungicides, cyproconazole, epoxiconazole, reproductive toxicity, antiandrogenic and antiestrogenic effects, Wistar Han rats.

scholarly journals Study of gonado- and reproductive toxicity of technical-grade carbendazim in male and female Wistar Han rats

2019 ◽  
Vol 84 (4) ◽  
pp. 36-41
Author(s):  
Ya.V. Kolianchyk
Keyword(s):  
Body Weight ◽  
Reproductive Toxicity ◽  
Reproductive Function ◽  
Female Rats ◽  
Dose Effect ◽  
Male Rats ◽  
Cycle Duration ◽  
Technical Grade ◽  
Male And Female ◽  
Functional Parameters

Objective. Identification of hazard and assessment of the risk of gonado- and reproductive toxicity of two generic pesticides of technical-grade carbendazim of different purity bin male and female Wistar Han rats. Materials and Methods. Carbendazim with the purity of 98 % (C1) and 98.1 % (C2) was intragastrically administered on the daily basis, excluding Saturday and Sunday, at the doses of 2.5 and 25 mg/kg body weight in three groups of animals (20 males and female rats in each) during 10 weeks (forfemales) and 11 weeks (for males). Control animals received an equivalent amount of the solvent. Intact animals intended for breeding were managed in parallel with the control and experimental animals. After the end of the exposure, functional parameters of the condition of gonads and reproductive ability of the animals were investigated. Females were used to investigate the condition of the oestral cycle, duration and frequency of each stage of it. The condition of the reproductive function in the female rats was considered at Day 20 of pregnancy. Indices of breeding, conception, fertility, pregnancy were established, and the duration of the pre-coitalperiod was considered. Results and Discussion. The data obtained suggest that exposure to two generic substances of carbendazim at the dose of 25 mg/kg body weight during 11 weeks is manifested in general toxic effect (body weight reduction) only in males upon exposure to C2. All test substances in the maximum dose have reproductive toxicity and show significant anti-androgenic action that is manifested as changes in the morphological and functional parameters of the condition of gonads in the experimental groups of male rats. Furthermore, the negative effect on the oestral cycle in experimental female rats exposed to C2 was noted. Conclusion. Based on the obtained results it can be concluded that all test samples of carbendazim have reproductive toxicity at the dose of 25 mg/kg body weight. No-observed-effect level (NOEL) for all test compounds is 2.5 mg/kg body weight. Dose-effect dependence was observed in the range of studies doses.

Toxic Effects of Aluminium on Female Reproductive System in Presence of Ethanol Coexposure

2021 ◽  
pp. 3809-3815
Author(s):  
Buddhadeb Ghosh ◽  
Ravi Kant Sharma ◽  
Suman Yadav ◽  
Ankita Randev
Keyword(s):  
Body Weight ◽  
Granulosa Cells ◽  
Reproductive Toxicity ◽  
Concomitant Administration ◽  
Exposure Period ◽  
Treated Group ◽  
Female Rats ◽  
Corpora Lutea ◽  
Combined Administration ◽  
Increasing Trends

Both aluminium and ethanol are pro-oxidants and toxic. Uncontrolled use of aluminium and increasing trends of ethanol consumption in India increased the chance of coexposure to aluminium and ethanol. There are possibilities, that both of them follow common mechanisms to produce reproductive toxicity. The present study was planned to identify the effects of aluminium administration on the microscopic structure of ovary and to clarify any possible protection conferred by the concomitant administration of ethanol. Sixteen female rats divided into one control and three experimental groups exposed to aluminium (4.2mg/kg body weight) and ethanol (1gm/kg body weight) for 3 months. After the exposure period, ovaries were processed for light microscopic examination. Ovary showed significant atretic follicles with degenerated ova and vacuolation. Rupture of zona pellucida in oocyte seen in aluminium treated animals. Ethanol treated group showing absence of growing follicles, increased large corpora lutea. Dilated and congested vessels were observed in the growing follicle. The effects of combined administration of aluminium and ethanol treated groups showed with acute degeneration of growing follicles, with desquamation of pyknotic granulosa cells and degenerated oocyte. Multiple vacuoles of degenerated granulosa cells with dilated congested vessels and edema seen. Hyaline material seen inside the degenerating follicles. It has been suggested that the ethanol induced augmentation of impacts of aluminium on the Ovary.

Toxicity Assessment of 4-Amino-2-Nitrotoluene

2013 ◽  
Vol 32 (2) ◽  
pp. 113-122 ◽  
Author(s):  
John T. Houpt ◽  
Glenn J. Leach ◽  
Larry R. Williams ◽  
Mark S. Johnson ◽  
Gunda Reddy
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
Toxicity Data ◽  
Adverse Effect Level ◽  
Effect Level

4-Amino-2-nitrotoluene (4A2NT; CAS 119-32-4) is a degradation product of 2,4-dinitrotoluene. The toxicity data on 4A2NT are limited. Therefore, we collected toxicity data from rats to assess environmental and human health effects from exposures. The approximate lethal dose for both sexes was 5000 mg/kg. A 14-day toxicity study in rats was conducted with 4A2NT in the feed at concentrations of 0, 125, 250, 500, 1000, and 2000 ppm. Based on a 14-day oral dose range toxicity study with 4A2NT in the feed, 2000 ppm was selected as highest concentration for a subsequent 90-day study. An oral 90-day subchronic toxicity study in rats was conducted with concentrations of 0, 500, 1000, or 2000 ppm of 4A2NT in the feed. The calculated consumed doses of 4A2NT in the feed were 0, 27, 52, or 115 mg/kg/d for males and 0, 32, 65, or 138 mg/kg/d for females. A no-observed adverse effect level could not be determined. The lowest observed adverse effect level was 27 mg/kg/d for males and 32 mg/kg/d for female rats based upon decreased body weight gain. The decreased body weight gain in male rats was the most sensitive adverse event observed in this study and was used to derive a benchmark dose (BMD). A BMD of 23.1 mg/kg/d and BMD with 10% effect level of 15.5 mg/kg/d were calculated for male rats, which were used to derive an oral reference dose (RfD). The human RfD of 1.26 μg/kg/d was derived using current United States Environmental Protection Agency guidelines.

scholarly journals Effects of lifelong intervention with an oligofructose-enriched inulin in rats on general health and lifespan

2008 ◽  
Vol 100 (6) ◽  
pp. 1192-1199 ◽  
Author(s):  
Pascale Rozan ◽  
Amine Nejdi ◽  
Sophie Hidalgo ◽  
Jean-François Bisson ◽  
Didier Desor ◽  
...  
Keyword(s):  
Body Weight ◽  
Survival Rate ◽  
Biological Markers ◽  
Female Rats ◽  
Male Rats ◽  
Standard Diet ◽  
Male And Female ◽  
Reduced Body ◽  
Male And Female Rats ◽  
And Biological Markers

Ageing is associated with changes in physiology and morphology; nutritional strategies to decrease morbidity and to prolong life are of high interest. The aim of the study was to investigate the effects of lifelong supplementation with an oligofructose-enriched inulin on morphological and biological markers and lifespan in male and female rats. Male and female rats, age 3 months, were randomised into two groups to receive either a diet with 10 % of an oligofructose-enriched inulin (Synergy1) or a standard diet (control) for 27 months. The rats were weighed every 2 weeks and their food intake was evaluated on four successive days every 4–6 weeks. Samples were taken at 12, 18 and 24 months of age. During the whole intervention period, male rats receiving Synergy1 (SYN1-M) displayed lower body weight, cholesterol and plasma triacylglycerolaemia compared with the controls (Cont-M). The survival rate at 24 months of age of SYN1-M rats was 35·3 % greater than that of Cont-M rats. In female rats, the Synergy1 supplementation (SYN1-F) group also reduced body weight, cholesterol and triacylglycerolaemia levels, but results were less consistent over the experiment. The survival rate at 24 months of age in SYN1-F rats was 33·3 % greater compared with that of the control (Cont-F) group. To conclude, lifelong intervention with Synergy1 improved biological markers during ageing and survival rate (lifespan) of rats.

Comparison of the acute hematotoxicity of 2-butoxyethanol in male and female F344 rats

2000 ◽  
Vol 19 (3) ◽  
pp. 185-192 ◽  
Author(s):  
B I Ghanayem ◽  
S M Ward ◽  
B Chanas ◽  
A Nyska
Keyword(s):  
Body Weight ◽  
Cell Volume ◽  
Weight Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mean Cell Volume ◽  
Male And Female ◽  
Male And Female Rats ◽  
Butoxyacetic Acid ◽  
F344 Rats

Administration of 2-butoxyethanol (BE) to rodents causes acute hemolytic anemia, and metabolic activation of BE to butoxyacetic acid (BAA) is required for the development of this effect. Recent studies have shown that female rats treated with BE exhibit a variety of histopathologic lesions that are absent in males and many of these lesions are attributed to the hemolytic effects of BE. Current studies were designed to compare the acute hematotoxicity of BE in male and female F344 rats. Rats were treated with 250 mg BE/kg body weight or water (control; 5 ml/kg) by gavage. At 4, 8, or 24 h after dosing, rats were anesthetized, blood was collected by cardiac puncture, and various blood parameters were measured. BE resulted in a time-dependent swelling of erythrocytes as evidenced by an early increase in hematocrit (Hct) and mean cell volume (MCV) in male rats. In contrast, increased Hct in female rats did not accompany an increase in MCV. It is likely that hemolysis was so severe at 4 h that Hct exhibited a decline in female rats at that time point. Subsequently, red blood cell (RBCs), hemoglobin concentration (Hgb), and Hct declined as hemolysis progressed. However, the onset of BE-induced hemolysis was faster in female compared to male rats. These effects were also associated with a significant increase in the spleen weight to body weight ratio. Blood smears were also prepared and morphological changes evaluated by light microscopy included stomatocytosis, spherocytosis, and schistocytosis. Furthermore, aggregation of RBCs in female rats as evidenced by increased formation of rouleaux was observed at 24 h after BE administration. These effects were observed earlier and more frequently in female rats. No differences in the sensitivity of RBCs obtained from male and female rats and exposed to butoxyacetic acid (BAA) in vitro was observed as determined by measuring the packed cell volume. In conclusion, these data suggest that female rats are more sensitive to hemolysis and morphological alterations of erythrocytes induced by BE during the first 24 h after exposure compared to males. It is likely that the greater sensitivity of female rats to BE effects on RBCs may account for the reported development of thrombosis and tissue infarction in female rats.

Reproductive Toxicity Study of Clarified Slurry Oil in the Rat

1995 ◽  
Vol 14 (2) ◽  
pp. 119-128 ◽  
Author(s):  
A. M. Hoberman ◽  
M. S. Christian ◽  
R. Roth ◽  
S. Lovre ◽  
F. Koschier
Keyword(s):  
Body Weight ◽  
Reproductive Toxicity ◽  
Reproductive Organ ◽  
Female Rats ◽  
Male Rats ◽  
Feed Consumption ◽  
Clinical Effects ◽  
Weight Losses ◽  
Male And Female Rats ◽  
Weight Gains

Clarified slurry oil (CSO, CAS #64741–62-4; also termed carbon black oil), a residual product from the fluidized catalytic cracker in petroleum refining, has the potential to be absorbed through the skin. The reproductive toxicity of CSO in male and female rats was evaluated by the topical route of exposure. CSO was administered dermally to male rats at dosages of 0 (vehicle), 0.1, 1, 10, 50, and 250 mg/kg/day for 70 days before a cohabitation period with untreated female rats. CSO was administered also to female rats at the same dosages for 14 days prior to a 7-day cohabitation period and continuing until Day 0 of gestation (day spermatozoa was present in a smear of the vaginal contents or a copulatory plug was observed in situ). The dosage volume in both experiments was 1 ml/kg, adjusted on each day of dosage based on individual body weights recorded immediately before application of CSO. Under the conditions of these experiments, the paternal no-observable-adverse-effect-level (NOAEL) for CSO administered dermally was 1 mg/kg/day. The 10, 50, and 250 mg/kg/day dosages of CSO caused body weight losses and/or decreased body weight gains and reduced feed consumption. The 50- and 250-mg/kg/day dosages also caused adverse clinical effects. No mating, fertility, or testicular end points in male rats were affected by the highest dosages tested; therefore, the reproductive NOAEL for male rats is <250 mg/kg/day. The maternal NOAEL for CSO administered dermally was 10 mg/kg/day. The 50-and 250-mg/kg/day dosages of CSO reduced body weight gains; 250 mg/kg/day also reduced feed consumption. There were no adverse effects on gonadal function, estrous cycles, mating behavior, conception rates, or reproductive organ weights; therefore, the reproductive NOAEL for female rats administered CSO dermally is at least 250 mg/kg/day.

Effects of corticotropin-releasing factor on energy balance in rats are sex dependent

1989 ◽  
Vol 257 (6) ◽  
pp. R1417-R1422 ◽  
Author(s):  
S. Rivest ◽  
Y. Deshaies ◽  
D. Richard
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Serum Testosterone ◽  
Corticotropin Releasing Factor ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Significant Difference

The purpose of this study was to investigate the effects of a chronic intracerebroventricular administration of corticotropin-releasing factor (CRF) on energy balance of male and female rats. One week after their delivery to the laboratory, both male and female rats were divided into two groups. One group in each sex was treated with human/rat CRF, while another group was infused with the vehicle. Chronic administration of CRF was accomplished by means of miniosmotic pumps connected to a cannula that was stereotaxically directed into the third ventricle. Food intake and body weight were measured each day during the study. After 14 days of treatment, the rats were killed by decapitation. Energy, fat, and protein contents of the carcasses were quantified. Serum testosterone and estradiol were assayed in males and females, respectively. Administration of CRF significantly reduced body weight gain and food intake in male rats. No significant difference in those variables was observed between female rats treated with CRF and their controls infused with saline. Similarly, metabolizable energy intake and body energy gain were reduced in male rats infused with CRF, whereas no difference was observed between female animals treated with CRF and those infused with saline. In male rats, body fat and body protein contents were lower in CRF-treated than in saline-infused rats. In female rats, CRF did not affect body composition. Serum testosterone in male rats and serum estradiol in female animals were reduced after chronic infusion of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of leptin on secretion of LH and FSH from primary cultured female rat pituitary cells

2001 ◽  
Vol 144 (6) ◽  
pp. 653-658 ◽  
Author(s):  
K Ogura ◽  
M Irahara ◽  
M Kiyokawa ◽  
M Tezuka ◽  
T Matsuzaki ◽  
...  
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Pubertal Development ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Pituitary Cells ◽  
Female Rat ◽  
Serum Leptin ◽  
Female Wistar Rats

BACKGROUND: Leptin, which is the product of the obese gene, is believed to play important roles in pubertal development and reproductive function in females. In a study using adult male rats, it was found that leptin stimulated secretion of gonadotropin from the pituitary in a dose-related manner. However, there has been no such study in female rats. OBJECTIVE: To investigate the effects of leptin on the production of LH and FSH from the pituitary in female rats, using primary cultured pituitary cells. METHODS: In this study, we determined body weight, serum leptin concentration and serum estradiol (E(2)) concentration in female Wistar rats at 3, 5, 6, 7, 9 and 11 weeks of age, and cultured pituitary cells from 6-week-old female Wistar rats with leptin (0--10(-7) mol/l) and GnRH (0 or 10(-8) mol/l). Then basal and GnRH-stimulated extra- and intracellular LH and FSH were assayed by RIA. RESULTS: Serum leptin concentration increased with increases in body weight and E(2) concentration. The pubertal serum leptin concentration was about 10(-10) mol/l. At a lower or moderate concentration, leptin produced dose-related increases in both basal and GnRH-stimulated extra- and intracellular LH and FSH in pituitary cells. At a concentration of 10 mol/l, leptin significantly (P<0.05) stimulated both basal and GnRH-stimulated extra- and intracellular LH and FSH. However, at greater concentrations, these effects diminished. CONCLUSIONS: These results indicated that leptin induced pituitary cells to produce and secrete both LH and FSH, with or without GnRH. The concentration of leptin that induced the greatest production of gonadotropins by pituitary cells was 10(-10) mol/l, which was the same as the physiological pubertal concentration. Leptin may be involved in the onset of puberty. It is also conceivable that leptin may be a cause of ovulatory failure, not only in weight loss but also in weight gain.

Toxicity and Carcinogenicity of T-Butyl a Lcohol in Rats and Mice Following Chronic Exposure in Drinking Water

1995 ◽  
Vol 11 (2) ◽  
pp. 151-165 ◽  
Author(s):  
Joseph D. Cirvello ◽  
Ann Radovsky ◽  
James E. Heath ◽  
Daniel R. Farnell ◽  
Charles Lindamood
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Female Rats ◽  
Male Rats ◽  
Follicular Cell ◽  
Male Mice ◽  
Cell Adenoma ◽  
Male And Female ◽  
Female Mice ◽  
Male And Female Rats

t-Butyl alcohol (TBA) was administered in drinking water to F344/N rats and B6C3F1 mice for two years using 60 animals/dose/sex/species. Male rats received doses of 0, 1.25, 2.5, or 5 mg/ml and females received 0, 2.5, 5, or 10 mg/ml, resulting in average daily doses of approximately 85, 195, or 420 mg TBA/kg body weight for males and 175, 330, or 650 mg/kg for females. Ten rats per group were evaluated after 15 months. Male and female mice received doses of 0, 5, 10, or 20 mg/ml, resulting in average daily doses of approximately 535, 1,035, or 2,065 mg TBA/kg body weight for males and 510, 1,015, or 2,105 mg/kg for females. Survival was significantly reduced in male rats receiving 5 mg/ml, female rats receiving 10 mg/ml, and male mice receiving 20 mg/ml. Long-term exposure to TBA produced increased incidences of renal tubule adenoma and carcinoma in male rats; transitional epithelial hyperplasia of the kidney in male and female rats; follicular cell adenoma of the thyroid in female mice; and follicular cell hyperplasia of the thyroid and inflammation and hyperplasia of the urinary bladder in male and female mice. In addition, a slight increase in follicular cell adenoma or carcinoma of the thyroid (combined) in male mice may have been related to the administration of TBA.

Trans-1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz-E) (2018)

2019 ◽  
Vol 35 (3) ◽  
pp. 204-210
Keyword(s):  
Body Weight ◽  
Female Rats ◽  
Male Rats ◽  
Repeated Dose ◽  
Exposure Level ◽  
Inhalation Study ◽  
Male And Female ◽  
Range Finding ◽  
Male And Female Rats ◽  
Dose Inhalation

Trans-1,1,1,4,4,4-hexafluoro-2-butene (HFO-133mzz-E) is an odorless gas that finds uses as a foam transfer agent, heat transfer fluid, and specialty gas. The acute 4-h LC50 (in rats) for HFO-133mzz-E is > 17,000 ppm; it was not an eye or dermal irritant in 3- and 13-week repeated-dose inhalation studies in rats at concentrations up to 1.5% (15,000 ppm). HFO-133mzz-E was not a cardiac sensitizer at 70,000 ppm in a standard epinephrine challenge study in Beagle dogs. In a 3-week, repeated-dose (non-GLP) inhalation range-finding study in male and female rats, HFO-133mzz-E concentrations of 7500 and 15,000 ppm were determined to be well-tolerated. In the follow-up, GLP-compliant, 28-day repeated-dose inhalation study (as per OECD 412), male and female rats were exposed to 0, 1000, 10,000, or 15,000/20,000 ppm (20,000 ppm concentration was decreased to 15,000 ppm after week 1 because of deaths and body weight loss). The study no-observed-adverse-effect level (NOAEL) was established at 10,000 ppm based on reduced body weight gain and mortality observed at 15,000 ppm. In a 90-day GLP-compliant repeated-dose study (as per OECD 413), male and female rats were exposed to 0, 1000, 5000, 7500, or 15,000 ppm HFO-133mzz-E. Three male rats exposed to 15,000 ppm HFO-133mzz-E died during exposure; clinical signs such as restlessness, blepharospasm, and myoclonic jerks were also observed, during the first month of the study, at 15,000 ppm. There were no significant gross or histopathological organ/tissue lesions attributable to HFO-133mzz-E exposure. The study NOAEL was established at 7500 ppm. In a GLP prenatal developmental study (OECD 414), groups of time-mated nulliparous female rats were exposed via inhalation to 0, 1000, 5000, 7500, or 15,000 ppm HFO-1336mzz-E beginning on gestation day (GD) 6 up to and including GD 19. Under the conditions of this study, the NOAEL for maternal and fetal effects was established at 7500 ppm. HFO-1336mzz-E was not genotoxic in either in vitro or in vivo assays. Based on the results of the 90-day inhalation study, 7500 ppm was determined to be the NOAEL and was selected as the point of departure for the derivation of the 8-h time-weighted average (TWA), health-based workplace environmental exposure level (WEEL) value. This subchronic inhalation NOAEL was adjusted to account for duration of exposure, interindividual variability, and intraindividual variability. The resulting 8-h TWA WEEL value of 400 ppm is fully expected to provide a significant margin of safety against the production of any potential adverse health effects in workers following long-term inhalation exposure to HFO-1336mzz-E.

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