Toxicology of Diethylene Glycol Butyl Ether 4. Dermal Subchronic/Reproduction Study in Rats

1993 ◽  
Vol 12 (2) ◽  
pp. 161-168 ◽  
Author(s):  
Carol S. Auletta ◽  
Raymond E. Schroeder ◽  
Walter J. Krasavage ◽  
Carol R. Stack
Keyword(s):  
Diethylene Glycol ◽  
Reproductive Toxicity ◽  
Occult Blood ◽  
Systemic Effect ◽  
Female Rats ◽  
Sprague Dawley ◽  
Butyl Ether ◽  
Growth And Survival ◽  
Male And Female Rats ◽  
Reproduction Study

The subchronic and reproductive toxicity of diethylene glycol butyl ether (DGBE) by the dermal route was evaluated in Sprague-Dawley rats using a novel combined protocol. DGBE was administered dermally at 10 or 30% v/v in aqueous solutions or undiluted (100%) for 13 weeks under occlusion, 6 hr/day, 5 days/week at a maximum attainable volume of 2 mL/kg. Satellite groups of male and female rats were treated with the top dose of DGBE for 13 weeks, mated, and the females were treated through day 20 of gestation and allowed to deliver and nurse their offspring through day 21 of lactation (weaning). DGBE produced dermal irritation, which was dependent on concentration in incidence, severity, and time of onset and was more severe in females than in males. No corresponding histopathology was evident. The only suggestion of a systemic effect was a slightly increased incidence of urinary occult blood at study termination in the females receiving the 30% or 100% DGBE dose. There was no evidence of histopathologic changes in the testes, and vaginal cytology indicated no adverse effect on estrous cycling. There were no effects on reproductive performance of the DGBE-treated males and females. Litters delivered by treated females contained the same number of live pups as control litters and the growth and survival of pups within the treated litters was comparable to control. No reproductive or systemic toxicity was observed at the highest dose tested—2 g/kg/day.

Toxicology of Diethylene Glycol Butyl Ether 5. Dermal Subchronic Neurotoxicity Study in Rats

1993 ◽  
Vol 12 (2) ◽  
pp. 169-174 ◽  
Author(s):  
P. Beyrouty ◽  
B. Broxup ◽  
G. Losos ◽  
K. Robinson ◽  
J. P.J. Maurissen ◽  
...  
Keyword(s):  
Motor Activity ◽  
Diethylene Glycol ◽  
Dose Group ◽  
Clinical Findings ◽  
The Body ◽  
Female Rats ◽  
Sprague Dawley ◽  
Butyl Ether ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

Groups of Sprague-Dawley rats were treated dermally with the vehicle, distilled water or with diethylene glycol butyl ether (DGBE) at 10 or 30% v/v aq. solutions or undiluted (0.2, 0.6, or 2.0 g/kg body weight) for 13 weeks under occlusion 6 hr/day, 5 days/week, at the maximum attainable volume of 2 mL/kg. Male and female rats were examined using a functional observational battery (FOB) prestudy, at 1, 6, and 24 hr after the initiation of the first exposure, and prior to treatment on days 7, 14, 35, 63, and 91. Motor activity was determined prestudy and on nontreated days 34, 62, and 90. At the completion of treatment, six control and top dose group animals were perfused for neuropathology. There was no mortality, and the body weights and food consumption were unaffected. Five females in the top dose group had scab formation at the treatment site during the study. There were no other treatment-related clinical findings. The FOB and motor activity tests revealed no findings indicative of a neurotoxic effect, and there were no gross or neuropathological changes that were attributed to treatment. No neurotoxicity or other systemic toxicity was seen at the highest dose tested—2 g/kg/day.

Reproductive Toxicity Screen of Ammonium Dinitramide Administered in the Drinking Water of Sprague-Dawley Rats

1995 ◽  
Vol 11 (4) ◽  
pp. 437-448 ◽  
Author(s):  
Edwin R. Kinkead ◽  
Robin E. Wolfe ◽  
Carlyle D. Flemming ◽  
Harold F. Leahy ◽  
Daniel J. Caldwell ◽  
...  
Keyword(s):  
Drinking Water ◽  
Histopathological Examination ◽  
Reproductive Toxicity ◽  
Female Rats ◽  
Litter Production ◽  
High Dose ◽  
Ammonium Dinitramide ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Pregnancy And Lactation

The Department of Defense is currently considering replacing ammonium perchlorate with ammonium dinitramide (ADN), a class 1.1 explosive oxidizer to be used in solid rocket propellant mixtures and explosives. This study was intended to evaluate the potential of ADN to produce alterations in paternal fertility, maternal pregnancy and lactation, and growth and development of offspring. Male and female rats received drinking water containing 0.0, 0.2, 1.0, or 2.0 g ADN/liter throughout the study. Mating occurred following 14 days of treatment. All dams, one-half the males, and representative pups were maintained for a total of 90 days of treatment. No mortality occurred in parental animals during the study. Treatment with ADN resulted in no adverse effects on mating; 92-100% of the animals mated. No treatment-related effects were seen in parental animals clinically or histopathologically. Adverse treatment-related effects were noted in maternal and paternal fertility indices, gestational indices, and live birth indices in both the mid- and high-dose groups. Litter sizes in themid- and high-dose groups were significantly smaller than those of the low-dose and control groups. Mean pup weights showed no statistically significant differences between ADN-treated pups and controls. Gross and histopathological examination of the animals failed to identify the cause for the decrease in litter production in the mid- and high-dose dams. This study indicates that ADN is a reproductive toxicant. The no-observable-effect level (NOEL) is 29 mg/kg/day, the median dose of the low-level female rats.

Toxicology of Diethylene Glycol Butyl Ether 2. Disposition Studies with 14C-Diethylene Glycol Butyl Ether and 14C-Diethylene Glycol Butyl Ether Acetate After Dermal Application to Rats

1993 ◽  
Vol 12 (2) ◽  
pp. 145-154 ◽  
Author(s):  
Rodney J. Boatman ◽  
Daniel B. Schum ◽  
Derek Guest ◽  
Carol R. Stack
Keyword(s):  
Aqueous Solution ◽  
Diethylene Glycol ◽  
Low Dose ◽  
Dermal Absorption ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Butyl Ether ◽  
Applied Dose ◽  
Washing Efficiency

Human dermal exposure to diethylene glycol butyl ether (DGBE) and its acetate derivative (DGBA) may occur through contact with a variety of commercial products. Absorption and elimination of dermally applied doses of 14C-DGBE and 14C-DGBA were determined in Sprague-Dawley rats. The materials were applied under occlusion for 24 hr at dose levels of 0.2 and 2.0 g/kg (undiluted) and as a 10% aqueous solution (0.2 g/kg DGBE). Preliminary washing efficiency studies with soap and water indicated that greater than 89% of each chemical could be removed from rat skin following 5-min exposures. Female rats excreted a larger proportion of the applied dose of DGBE than did male rats. Similar results were obtained with the low dose of DGBE applied neat or as a 10% aqueous solution, suggesting that the low dose represents a saturating dose. The total recovered 14C for all studies with 14C-DGBE ranged from 83% to 89%, with 14C-DGBA, from 80% to 88%. Urinary excretion accounted for the majority of recovered 14C in all studies. The acid, 2-(2-butoxyethoxy)acetate acid was the major urinary metabolite identified. The glucuronide of DGBE was present at levels of from 5.2 to 8.2% of the urinary 14C. The dermal absorption rates were estimated to be 1.58 (DGBA, male), 1.28 (DGBA, female), 0.73 (DGBE, male), and 1.46 (DGBE, female), expressed as mg/cm2/hr.

Oral 1-Generation Rat Reproduction Study of Isobornyl Acetate: An Evaluation Through Sexual Maturity in the F1 Generation

2017 ◽  
Vol 36 (3) ◽  
pp. 252-259 ◽  
Author(s):  
Valerie T. Politano ◽  
Elise M. Lewis ◽  
Alan M. Hoberman ◽  
Robert M. Diener ◽  
Anne Marie Api ◽  
...  
Keyword(s):  
Sexual Maturity ◽  
Ovarian Follicle ◽  
Reproductive Toxicity ◽  
Clinical Signs ◽  
Female Rats ◽  
Feed Consumption ◽  
Male And Female Rats ◽  
Body Weights ◽  
Reproduction Study ◽  
F1 Generation

Reproductive toxicity of isobornyl acetate (IA), a widely used fragrance ingredient, was investigated in a 1-generation reproduction study in which 25 Crl: CD (Sprague-Dawley) rats/sex/group were gavaged with dosages of 0 (corn oil vehicle), 30, 100, or 300 mg/kg/d during premating, mating, gestation, and lactation. After weaning, 25 F1 generation pups/sex/dosage group were randomly selected for evaluation until sexual maturity. The following parameters were evaluated in P generation males and females: viability, clinical signs, body weights, feed consumption, mating and fertility, organ weights, gross and microscopic observations, sperm assessments (motility and concentration), natural delivery and litter observations, and ovarian follicle counts. In F1 generation pups, viability, body weights, sexual maturation, anogenital distance (days 1 and 22 postpartum), nipple eruption (day 12 postpartum), and gross necropsy observations were recorded. Isobornyl acetate did not adversely affect any of the investigated parameters. Based on the results of this investigation, the no observable adverse effect level (NOAEL) for toxicity of IA is considered to be 300 mg/kg/d. Increased incidences of excess salivation occurred in P generation male and female rats at 100 and/or 300 mg/kg/d throughout the dosage period, and low incidences of urine-stained abdominal fur were seen in females at 300 mg/kg/d during the gestation period. These clinical signs were not considered as adverse effects of IA administration. Thus, the NOAEL for reproductive toxicity in the P generation rats and the NOAEL for viability and growth of the F1 generation offspring is considered to be ≥300 mg/kg/d.

scholarly journals Toxicity Evaluation of a Traditional Polyherbal Unani Formulation Jawarish Shahi in Rats

2018 ◽  
Vol 7 (5) ◽  
pp. 412-418
Author(s):  
Mohd Urooj ◽  
◽  
Mohammad Ahmed Khan ◽  
G. Thejaswini ◽  
Munawwar Husain Kazmi ◽  
...  
Keyword(s):  
Body Weight ◽  
Feed Intake ◽  
Clinical Signs ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Male And Female ◽  
Salix Caprea ◽  
Male And Female Rats ◽  
Dose Levels

Jawarish Shahi (JS) is a compound polyherbal Unani pharmacopoeial formulation indicated for Khafqan (Palpitation), Nafkh-e-Shikam (Flatulence) and Waswas (Insanity; false perception and hallucinations). Jawarish Shahi contains herbs like Halela (Terminalia chebula), Amla (Emblica officinalis), Kishneez (Coriandrum sativum), Elaichi Khurd, (Elettaria cardamomum), and Bed Mushk (Salix caprea). The present study was carried out as per OECD 408 guidance to evaluate 90 days repeated oral dose toxicity in male and female Sprague Dawley rats. The study was performed at dose levels 1028 and 2000 mg/kg bw. No adverse effects were reported with respect to body weight, feed intake, behavior and clinical signs indicative of systemic toxicity. The expected growth pattern was observed in body weight and feed intake as compared to control group at both dose levels in male and female rats. There were few significant alterations with respect to hematology, and clinical biochemistry, however the results were within normal range thus considered toxicologically insignificant. The microscopic examination of different organ/tissue showed that no histopathological changes were observed. The findings of the study showed that No Observed Adverse Effect Level (NOAEL) for JS is greater than 2000 mg/kg body weight

Dietary Administration of Colesevelam Hydrochloride Does Not Affect Fertility or Reproductive Performance in Rats

2004 ◽  
Vol 23 (6) ◽  
pp. 357-367 ◽  
Author(s):  
Judith K. Marquis ◽  
Rafif Dagher ◽  
Michael R. Jones
Keyword(s):  
Reproductive Performance ◽  
Sperm Count ◽  
Embryo Implantation ◽  
Sperm Concentration ◽  
Study Groups ◽  
Female Rats ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Total Percentage ◽  
Male And Female Rats

Colesevelam hydrochloride (HCl) (WelChol; Sankyo Pharma) is a novel, highly potent, bile acid-binding polymer used for the treatment of hypercholesterolemia. The primary aim of this study was to determine the effects of dietarily administered colesevelam HCl on fertility and reproductive performance parameters. To assess these effects, sexually mature Sprague-Dawley rats were randomized to one of five treatment groups: feed alone, feed plus control article (SigmaCell), or feed plus colesevelam HCl 200, 1000, or 2000 mg/kg/day. Male and female rats were administered the appropriate group agent for 28 and 15 days, respectively, and were subsequently paired together for cohabitation and mating. Females continued to receive the test agent in their dietary formulation through presumed gestation day (GD) 7. Presumed pregnant females underwent cesarean section on GD 20. Food consumption rate, body weight, gross necropsy, and standard preclinical tests for reproduction and fertility were performed for each test animal. No statistically significant differences were found between control and drug-treated groups for any tested endpoints of reproduction. All animals placed in cohabitation successfully mated. Uterine and litter end points were unaffected by dosages of colesevelam HCl as high as 2000 mg/kg/day. There were no significant differences between treatment group litter averages in the number of corpora lutea, implantation sites, litter size, live fetuses, body weights, early/late resorptions, and the number of dams with viable fetuses. In addition, no external alterations of fetal morphology were attributable to treatment with colesevelam HCl when administered up to the embryo implantation stage. In male animals, no significant differences were found between the colesevelam HCl and control study groups in the average caudal epididymal sperm count or sperm concentration, total number of motile and nonmotile sperm, and the total percentage of motile sperm. Based on these data, colesevelam HCl does not have any significant adverse reproductive or fertility effects in rats, even when administered at doses approximately 30 times greater than the approved clinical dose.

scholarly journals A Safety Evaluation of a Nature-Identical l-Ergothioneine in Sprague Dawley Rats

2016 ◽  
Vol 35 (5) ◽  
pp. 568-583 ◽  
Author(s):  
Palma Ann Marone ◽  
Jan Trampota ◽  
Steven Weisman
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Antioxidant Properties ◽  
Metabolic Activation ◽  
Female Rats ◽  
Systemic Absorption ◽  
Test Substance ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1.58, 5, 15.8, 50, 158, 500, 1,580, and 5,000 μg/plate with and without metabolic activation, no cytotoxicity or mutagenicity was observed. Following a preliminary 28-day study, a repeated dose 90-day gavage study at dose levels of 0, 400, 800, and 1,600 mg/kg body weight (bw)/d in Sprague Dawley rats, in which dose-proportional systemic absorption was confirmed by plasma analysis, no adverse clinical, body weight/gain, food consumption and efficiency, clinical pathology, or histopathological changes associated with the administration of the nature-identical ergothioneine were observed. In conclusion, EGT+ administered over 90 days was well tolerated with a no adverse effect level at 1,600 mg/kg bw/d, the highest dose tested for male and female rats. In addition, the nature-identical test substance, EGT+ was not mutagenic in a bacterial reverse mutation assay at plate concentrations of up to 5,000 μg/mL in the presence or absence of metabolic activation.

scholarly journals Absorption, Distribution, Excretion, and Pharmacokinetics ofC-Pyronaridine Tetraphosphate in Male and Female Sprague-Dawley Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Hyun Park ◽  
Kannampalli Pradeep
Keyword(s):  
Clinical Trials ◽  
Small Intestine ◽  
Oral Administration ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Phase Ii Clinical Trials ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Peak Value

The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) ofC-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards.C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion ofC-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that theCmax, AUC (0-inf), andTmaxvalues were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.

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.

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