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

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.

1982 ◽  
Vol 53 (5) ◽  
pp. 1234-1238 ◽  
Author(s):  
D. Parsons ◽  
M. Riedy ◽  
R. L. Moore ◽  
P. D. Gollnick

The influence of fasting on fiber number in the soleus muscle (SM) of weanling male and female rats was investigated. For female rats, comparisons were made among groups of animals fed normally, rats fasted and then fed until prefast body weight was regained, and animals that grew to maturity. For male rats, comparisons were made only between control and fasted groups. Prior to the experimental treatments the SM was surgically removed from one leg. There was a 40% loss in body weight after fasting. Although major weight losses occurred in most muscles and organs, there was no change in the SM. Over the same period SM weight increased 31% in normal animals. Total fiber number (direct counts after nitric acid digestion) was unaltered by the treatments. Although wide variation existed between animals, total fiber number between legs for the same animal was closely correlated (r = 0.98). SM weight for male rats calculated from fiber length, cross-sectional area, and total fiber number could account for from 91 to 99% of the total muscle weight. There was no change in fiber number from weaning to maturity. It is concluded that fiber number is unchanged by fasting or during normal maturation.


2021 ◽  
Vol 54 (1) ◽  
pp. 52-61
Author(s):  
NR Shepelskaya ◽  
YaV Kolyanchuk

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.


2008 ◽  
Vol 100 (6) ◽  
pp. 1192-1199 ◽  
Author(s):  
Pascale Rozan ◽  
Amine Nejdi ◽  
Sophie Hidalgo ◽  
Jean-François Bisson ◽  
Didier Desor ◽  
...  

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.


Reproduction ◽  
2001 ◽  
pp. 915-924 ◽  
Author(s):  
L Pinilla ◽  
LC Gonzalez ◽  
F Gaytan ◽  
M Tena-Sempere ◽  
E Aguilar

Selective oestrogen receptor modulators constitute a family of drugs that are used increasingly in the management of oestrogen-associated pathology. Raloxifene is a selective oestrogen receptor modulator that is used to treat and prevent osteoporosis in post-menopausal women. The actions of raloxifene on bone, breast, uterus and serum cholesterol concentrations have been widely analysed, but very few studies have investigated the possible actions of this drug on the central nervous system. The central nervous system of the newborn rat is very sensitive to oestrogen action. In this study a series of experiments was conducted to analyse the effects of different doses of raloxifene (50, 100, 250 or 500 microg per rat per day) administered to neonatal rats on days 1-5 of age. Female rats treated with raloxifene showed decreased gonadotrophin secretion, hyperprolactinaemia, advanced vaginal opening, decreased body weight, persistent presence of cornified epithelial cells in vaginal smears, anovulation, inhibition of positive feedback between oestradiol and LH, and infertility. Male rats showed delayed balanopreputial separation, reduced body weight and hyperprolactinaemia. All these changes resemble those obtained after neonatal administration of oestradiol benzoate, thus indicating, for the first time, that raloxifene exerts an oestrogenic action on the hypothalamic-pituitary structures controlling reproductive function in rats.


2000 ◽  
Vol 19 (3) ◽  
pp. 185-192 ◽  
Author(s):  
B I Ghanayem ◽  
S M Ward ◽  
B Chanas ◽  
A Nyska

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.


1964 ◽  
Vol 207 (3) ◽  
pp. 631-633 ◽  
Author(s):  
David Kritchevsky ◽  
Shirley A. Tepper

Changes in serum cholesterol levels with age have been studied in male and female rats of three inbred strains (BN, DA, and Lewis) and one random-bred strain (Wistar). The mean serum cholesterol levels at each age differed among strains. Serum cholesterol levels (mg/100 ml) for male rats at 30, 60, and 90 days were: BN-65, 46, and 47; DA-105, 85, and 101; Lewis-79, 76, and 57; and Wistar-64, 63, and 73. For female rats the values were: BN-56, 45, and 47; DA-86, 74, and 91; Lewis-77, 83, and 67; and Wistar-59, 71, and 83. The variation of serum cholesterol with age was different between strains, but similar for males and females within each strain. There was no correlation between body weight and serum cholesterol. Liver cholesterol levels (mg/100 g) determined at 90 days were, for the males, BN-187, DA-233, Lewis-247, and Wistar-300, and for the females, BN-188, DA-244, Lewis-216, and Wistar-249. No correlation with body weight or serum cholesterol was observed.


2002 ◽  
Vol 21 (4) ◽  
pp. 237-276 ◽  
Author(s):  
M. S. Christian ◽  
R. G. York ◽  
A. M. Hoberman ◽  
J. Frazee ◽  
L. C. Fisher ◽  
...  

In a two-generation study of dibromoacetic acid (DBA), Crl SD rats (30 rats/sex/group/generation) were provided DBA in drinking water at 0 (reverse osmosis-deionized water), 50,250, and 650 ppm (0,4.4 to 11.6,22.4 to 55.6, and 52.4 to 132.0 mg/kg/day, respectively; human intake approximates 0.1 μg/kg/day [0.0001 mg/kg/day]). Observations included viability, clinical signs, water and feed consumption, body and organ weights, histopathology, and reproductive parameters (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios and viabilities, maternal behaviors, reproductive organ weights, sperm parameters and implantation sites, sexual maturation). Histopathological evaluations were performed on at least 10 P and F1 rats/sex at 0 and 650 ppm (gross lesions, testes, intact epididymis; 10 F1 dams at 0, 250, and 650 ppm for primordial follicles). Developmental observations included implantations, pup numbers, sexes, viabilities, body weights, morphology, and reproductive performance. At 50 ppm and higher, both sexes and generations had increased absolute and relative liver and kidneys weights, and female rats in both generations had reduced absolute and relative adrenal weights; adrenal changes were probably associated with physiological changes in water balance. The livers and kidneys (10/sex/group/generation) had no histopathological changes. Other minimal effects at 50 ppm were reduced water consumption and a transient reduction in body weight. At 250 and 650 ppm, DBA reduced parental water consumption, body weight gains, body weights, feed consumption, and pup body weights. P and F1 generation male rats at 250 and 650 ppm had altered sperm production (retained step 19 spermatids in stages IX and X tubules sometimes associated with residual bodies) and some epididymal tubule changes (increased amounts of exfoliated spermatogenic cells/residual bodies in epididymal tubules, atrophy, and hypospermia), although inconsistently and at much lower incidences. Unilateral abnormalities of the epididymis (small or absent epididymis) at 650 ppm in four F1 generation male rats were considered reproductive tract malformations. The no-observable-adverse-effect level (NOAEL) and reproductive and developmental NOAELs for DBA were at least 50 ppm (4.5 to 11.6 mg/kg/day), 45,000 to 116,000 times the human adult exposure level. Reproductive and developmental effects did not occur in female rats exposed to DBA concentrations as high as 650 ppm. Based on the high multiples of human exposure required to produce effects in male rats, DBA should not be identified as a human reproductive or developmental risk.


1974 ◽  
Vol 31 (2) ◽  
pp. 147-157 ◽  
Author(s):  
E. L. Hove ◽  
Evelyn Lohrey ◽  
M. K. Urs ◽  
R. M. Allison

1. Protein concentrates were prepared from freshly cut lucerne by the Pirie process and freeze-dried. When supplemented with methionine or cystine and given to rats as the sole source of protein at 120 g protein/kg diet, the adjusted mean protein efficiency ratio was 2.89 (casein standard at 2.50). As a supplement to protein from barley meal the lucerne leaf-protein concentrate (LPC) was similar to casein.2. To investigate nutritional safety, lucerne LPC supplemented with methionine was given to rats at high levels for 6 months; exposure of these rats to diffuse daylight was avoided to prevent a severe disfiguring photosensitivity reaction. At a dietary protein concentration of 100 g/kg, rats grew equally well with lucerne LPC or casein. When the supplement was given at protein concentrations of 200 or 300 g/kg the rates of body-weight gain of male and female rats were less than those of control rats given casein. However, after 5 months on the diets, body-weights of male rats had nearly reached those of the controls.3. Apparent protein digestibility ratio was about 0.80 with all three levels of lucerne LPC.4. Reproduction was normal in seventeen of the eighteen female rats given the lucerne LPC at the three levels; lactation was also normal and litters were successfully raised to weaning.5. Organ weights, liver histology and blood haemoglobin were normal in male rats given the lucerne LPC for 6 months.6. Total body lipid of male rats given lucerne LPC was about half that of the control rats given casein. Body protein was slightly increased, and moisture content was higher in rats given lucerne LPC.7. The ‘whey’ remaining after precipitation of the protein from lucerne juice strongly inhibited the initial growth of mice given a complete control diet. The mice soon accommodated to the depressive effect of ‘whey’, and body-weight gains were normal during the 3rd week.


1989 ◽  
Vol 257 (6) ◽  
pp. R1417-R1422 ◽  
Author(s):  
S. Rivest ◽  
Y. Deshaies ◽  
D. Richard

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)


2009 ◽  
Vol 87 (4) ◽  
pp. 310-317 ◽  
Author(s):  
Erkan Tuncay ◽  
Ali Aytac Seymen ◽  
Pinar Sam ◽  
Hakan Gurdal ◽  
Belma Turan

In heart disease, differences exist between women and men with respect to the impact of risk factors, symptoms, and therapeutic responses. The use of β-adrenergic receptor blockers is now well established in the treatment of mild and moderate systolic heart failure. Although there are significant differences among agents, their clinical effects are predictable. To address the question of sex disparities in the heart, however, we investigated the effect of treatment with the nonselective β-blockers timolol and propranolol on mechanical and electrical function of heart preparations from male and female rats. We examined the long-term effects of intragastric treatment with timolol (5 mg/kg per day) or propranolol (25 mg/kg per day) for 7 months on the hemodynamic and intracellular action potential parameters of the heart. Chronic administration of timolol but not propranolol produced a significant increase in the baseline activity of the left ventricular developed pressure (LVDP) in both male and female rats with no significant effect on the left ventricular end-diastolic pressure. Timolol or propranolol treatment of male rats and timolol but not propranolol treatment of female rats induced significant shortening in the repolarization phases of action potentials recorded from left ventricular papillary muscle strips of the hearts. The responses of LVDP to β-adrenergic stimulation were similar in timolol- or propranolol-treated or untreated male rats. On the other hand, timolol treatment markedly increased, and propranolol treatment significantly decreased, the responses of increase in LVDP in female rats. Our results suggest that although treatment with β-blockers for 7 months confirmed the role of the β-adrenergic pathway in heart function, there are marked differences in the effects of individual β-blockers on heart physiology. Sex differences should be taken into consideration when using β-blockers during experimental studies and clinical therapy.


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