Inhalation Toxicology of Octamethylcyclotetrasiloxane (D4) Following a 3-Month Nose-Only Exposure in Fischer 344 Rats

2002 ◽  
Vol 21 (1) ◽  
pp. 39-53 ◽  
Author(s):  
Leigh Ann Burns-Naas ◽  
Robert G. Meeks ◽  
Gary B. Kolesar ◽  
Richard W. Mast ◽  
Michael R. Elwell ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Inhalation Exposure ◽  
Female Reproductive Tract ◽  
Female Rats ◽  
Serum Chemistry ◽  
Fischer 344 Rats ◽  
Histopathological Changes ◽  
Male And Female ◽  
Fischer 344 ◽  
Toxicological Significance

Octamethylcyclotetrasiloxane (D4) is a low-molecular-weight cyclic siloxane used primarily in the synthesis of silicone polymers. The objective of the present study was to evaluate the subchronic toxicity of D4 following a 3-month nose-only inhalation exposure. Male and female Fischer 344 rats (20/sex/group) were exposed 6 h/day, 5 days/week for 3 months to vapor concentrations of 0, 35, 122, 488, and 898 ppm D4. Also, an additional 10 per sex in the control and high-exposure groups were allowed a 4-week recovery period to observe reversibility, persistence, or delayed occurrence of any potential adverse effects. Body weights and food consumption were monitored at least twice weekly over the course of exposures. Approximately 18 hours preceding euthanasia, animals were transferred into metabolism cages for urine collection, and were fasted. At necropsy, rats were anesthetized with pentobarbital and euthanized by exsanguination. Blood was collected for hematological and clinical biochemical analyses. Selected organ weights were measured and a complete set of tissues was taken for histopathological examination. A concentration-dependent increase in absolute and relative liver weight (488 to 898 ppm) and a significant decrease in ovarian weight (898 ppm) were observed in female rats. Exposure to D4 via nose-only inhalation (35 to 898 ppm) produced minor alterations in hematological and serum chemistry parameters that were considered either incidental and of little toxicological significance (hematology) or suggestive of metabolic adaptation/alteration (serum chemistry) in response to exposure-related hepatomegaly. There were no histopathological findings noted in the liver. Histopathological evidence indicated the primary target organs following D4 inhalation exposure to be components of the female reproductive tract. Reversible histopathological changes were observed in the ovary (hypoactivity) and vagina (mucification) of female rats in the high-dose group only (898 ppm). Although an increase in the incidence and severity of both macrophage accumulation, interstitial inflammation, and eosinophil infiltration was observed in the lungs of male and female rats exposed to D4, the toxicological significance is uncertain as other inhalation studies at similar concentrations failed to show these effects. In summary, nose-only inhalation of a high concentration of D4 resulted in reversible histopathological changes in the female rat reproductive tract. Lower concentrations did not elicit these same effects.

Central neurotoxicity induced by subchronic exposure to 2,4-pentanedione vapour

1995 ◽  
Vol 14 (8) ◽  
pp. 662-671 ◽  
Author(s):  
RH Garman ◽  
DE Dodd ◽  
B. Ballantyne
Keyword(s):  
Electron Microscopy ◽  
Vestibular Nuclei ◽  
Brain Lesions ◽  
Female Rats ◽  
Male Rats ◽  
Fischer 344 Rats ◽  
Male And Female ◽  
Fischer 344 ◽  
Peripheral Nerve Lesions ◽  
Microscopical Evidence

1 Male and female Fischer 344 rats were exposed to 2,4- pentanedione (2,4-PD) vapour acutely (4 h) at 1265 or 1811 ppm, or for 6 h day-1 , 5 days a week for 14 weeks to 0, 101, 307 or 650 ppm. 2 Mortality occurred during or within a few hours of the acute exposures (10% at 1265 ppm; 70% at 1811 ppm). No animal had gross or microscopic brain lesions. 3 All female rats (20) and 10 of 30 male rats exposed to 650 ppm 2,4-PD vapour died by the 38th study day (29 exposures); there were no subsequent male deaths. Twenty-five of the 30 animals that died, and seven of the 15 males that survived, had light microscopical evidence of degenerative lesions, principally within the caudate/putamen nuclei, nuclei of the cerebellar medulla, and vestibular nuclei. Less frequently involved, in animals that died, were various regions of the cerebral cortex. The early histopathological lesions, seen from the 16th study day (12 exposures) to the 38th study day (28 exposures) were characterised by malacia. When present, lesions in male rats surviving the 14-weeks of 650 ppm 2, 4-PD expo sure were characterised by malacia and gliosis. No peripheral nerve lesions were seen by light or transmis sion electron microscopy. 4 Neither mortality nor neuropathology were seen in rats subchronically exposed to 101 or 307 ppm, 2,4-PD vapour.

Comparison of long-term feeding pattern between male and female Fischer 344 rats: influence of estrous cycle

1996 ◽  
Vol 270 (2) ◽  
pp. R413-R419 ◽  
Author(s):  
A. Laviano ◽  
M. M. Meguid ◽  
J. R. Gleason ◽  
Z. J. Yang ◽  
T. Renvyle
Keyword(s):  
Weight Gain ◽  
Food Intake ◽  
Estrous Cycle ◽  
Meal Size ◽  
Female Rats ◽  
Fischer 344 Rats ◽  
Male And Female ◽  
Fischer 344 ◽  
Males And Females

We studied the effect of gender on food intake, meal number, and meal size in eight 10-wk-old female and seven age-matched male Fischer 344 rats for 44 consecutive days. Although food intake (g/100 g body wt) was similar in males and females (5.42 +/- 0.10 vs. 5.13 +/- 0.13 g food.day-1.100 g body wt-1, respectively; not significant), weight gain in males was approximately seven times greater than in female rats (1.49 +/- 0.07 vs. 0.21 +/- 0.03 g/day, respectively; P < 0.001). During this time, males had a relatively constant food intake. They increased their meal size but decreased their meal number. In female rats, food intake was relatively stable for the duration of the study, despite cyclically and reciprocally recurring changes in meal number and meal size, which are synchronized with the estrous cycle. Data confirm that net food intake is a dynamic process and suggest that, in the rat, the homeostasis of food intake in response to external as well as internal stimuli is maintained via the modulation of meal number and size.

Calcium/phosphorus ratios of femurs of male and female fischer-344 rats exposed to halocarbon 27-S

1988 ◽  
Vol 46 ◽  
pp. 338-339
Author(s):  
D.R. Mattie ◽  
J.J. Maslanka ◽  
C.D. Flemming
Keyword(s):  
Bone Matrix ◽  
Female Rats ◽  
Fischer 344 Rats ◽  
Inorganic Fluoride ◽  
Male And Female ◽  
X Ray ◽  
Analysis Techniques ◽  
Fischer 344 ◽  
Male And Female Rats ◽  
Calcium Phosphorus

Halocarbon 27-S (H 27-S) is a polymer of chlorotrifluoroethylene (CTFE). Since metabolism of CTFE yields inorganic fluoride, it was believed that H 27-S would also yield fluoride in the blood. Exposure to fluorine results in deposition in bone as calcium fluoride or fluorapatite. Deposition of fluoride in the bone matrix should result in an altered calcium phosphorus ratio (CaP). The objective of this study was to determine the CaP of femurs of male and female rats exposed subchronically to H 27-S using energy dispersive x-ray analysis techniques and to compare CaP from exposed rats with the CaP of control rats.Male and female rats were dosed daily with 2.5 g H 27-S/kg body weight by gavage for 7 or 21 days. Rats were sacrificed at 7, 21 and 35 days (14 days after the 21 day dosing). Femurs of three rats of each sex and each group were analyzed.

Subchronic Studies of Triprolidine in Fischer 344 Rats

1993 ◽  
Vol 12 (4) ◽  
pp. 359-367
Author(s):  
Carlton D. Jackson ◽  
Gerald M. Cronin ◽  
Richard J. Brown
Keyword(s):  
Female Rats ◽  
Fischer 344 Rats ◽  
Fatty Change ◽  
Subchronic Toxicity ◽  
Male And Female ◽  
Fischer 344 ◽  
Male And Female Rats ◽  
Target Organs ◽  
Body Weights ◽  
Males And Females

Triprolidine, used extensively as an antihistamine, was studied for subchronic toxicity by administration as an admixture in the diet to male and female Fischer 344 rats at dosage levels of 0, 156, 312, 625, 1250, and 2500 parts per million (ppm) for 14 days and in a second study at 0, 250, 500, 1000, 2000, and 4000 ppm for 90 days. In the 14-day study, the only sign of toxicity observed either clinically or histologically was a reduction of final body weights (less than 10%) of both male and female rats in the 2500 ppm dosage group associated with reduced food consumption. In the 90-day study, final body weights were reduced, compared to controls, at the higher dosage levels with 4000 ppm resulting in a 20% and 13.4% reduction in males and females, respectively. Target organs were identified as the liver with hepatic fatty change and the parotid salivary gland, which exhibited treatment-related cytoplasmic alterations of the acinar cells. Males were more susceptible than females to both of these effects. These results indicate that rats would tolerate 2000 ppm triprolidine in a 2-year chronic bioassay without significant shortening of life span.

Chlorotrifluoroethylene (CTFE) Oligomer: Effect on Livers of Fischer-344 Rats

1988 ◽  
Vol 46 ◽  
pp. 330-331
Author(s):  
D.R. Mattie ◽  
M.R. Chase ◽  
E.R. Kinkead ◽  
R.E. Whitmire
Keyword(s):  
Electron Microscopic Examination ◽  
Exposure Period ◽  
Electron Microscopic Investigation ◽  
Female Rats ◽  
Toxicity Tests ◽  
Fischer 344 Rats ◽  
Electron Microscopic ◽  
Male And Female ◽  
Fischer 344 ◽  
Male And Female Rats

Chlorotrifluoroethylene (CTFE) oligomer is a nonflammable, saturated, hydrogen-free halocarbon oil with chain lengths of six to ten carbons. CTFE was seen to have a low degree of toxicity in acute toxicity tests. A subchronic study was conducted because CTFE is an excellent candidate hydraulic fluid. The objective of this electron microscopic investigation was to examine and compare the livers of male and female rats after inhalation exposure to CTFE for 90 days.Male and female Fischer-344 rats were exposed to 0.25, 0.5, or 1.0 mg/L CTFE aerosol for 90 days, 6 h/day, 5 days/week. An equal number of control rats were exposed to air only. Following the 90-day exposure period, 10 male and 10 female rats were sacrificed from each group. A 1mm slice of the left lobe of the liver of three rats of each sex and each group was collected for transmission electron microscopic examination.

12-Month Chronic Toxicity Study of LY275585 (Human Insulin Analog) Administered Subcutaneously to Fischer 344 Rats

1997 ◽  
Vol 16 (6) ◽  
pp. 639-657 ◽  
Author(s):  
J. L. Zimmermann ◽  
L. L. Truex
Keyword(s):  
Low Dose ◽  
Serum Triglyceride ◽  
Serum Glucose ◽  
Female Rats ◽  
Food Utilization ◽  
Fischer 344 Rats ◽  
Male And Female ◽  
Fischer 344 ◽  
Male And Female Rats ◽  
Males And Females

The monocomponent insulin analog LY275585 was administered to Fischer 344 rats in daily subcutaneous doses of 0, 20, or 200 U/kg for 12 months. Each treatment group consisted of 30 males and 30 females, and the vehicle control group consisted of 35 of each sex. Changes related to the pharmacologic activity of LY275585 included an increase in body weight, body weight gain, food consumption, and efficacy of food utilization in male and female rats given 200 U/kg. Pharmacologically related clinical chemistry effects occurring at 200 U/kg were an increase in mean serum glucose (24 h postdose) of males and females, a slight decrease in mean serum triglyceride of females, and decreased mean serum cholesterol of males and females. Fewer effects occurred in low-dose rats (20 U/kg) and included an increase of efficiency of food utilization only in female rats, a slight decrease in mean serum triglyceride in females, and decreased mean serum cholesterol in low-dose males and females. Three male and two female rats administered 200 U/kg died during the treatment period. Death of one male was attributed to hypoglycemia. Cause of death of four other high-dose rats was either not apparent, or the result of a variety of intercurrent disease processes unrelated to treatment. Survival in the low-dose (20 U/kg) and control groups was similar; one rat in each group died prior to treatment termination. The only compound-related lesion associated with treatment was a non-dose-related enhancement of the degree and incidence of inflammation at the site of subcutaneous injection. There were no compound-related changes in background lesions including neoplasms, or in hematologic or urinalysis values. In a comparison study, pharmacokinetic profiles of LY275585 and serum glucose values were determined in groups of 30 male and female rats administered single doses of 20 or 200 U/kg. Plasma levels of LY275585 peaked after 30 min, were dose related, and were similar in male and female rats. The hypoglycemia produced in rats receiving a single dose of 20 U/kg was maximal, suggesting saturation of the insulin receptor sites at this dose. The dose of 200 U/kg of LY275585 was, therefore, a supramaximal pharmacological dose when compared to an average daily human dose of 0.5 U/kg/ d. It is concluded that no toxicologically significant changes, other than moderate injection site inflammation, occurred in Fischer 344 rats treated with LY275585 at doses of 20 and 200 U/kg for 12 months.

Toxic effects of inhaled DMMP on the kidneys of Fischer-344 rats

1987 ◽  
Vol 45 ◽  
pp. 880-881
Author(s):  
D.R. Mattie ◽  
C.J. Hixson
Keyword(s):  
Left Kidney ◽  
Inhalation Exposure ◽  
Electron Microscopic Examination ◽  
Exposure Period ◽  
Male Rats ◽  
Continuous Exposure ◽  
Fischer 344 Rats ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Fischer 344

Dimethylmethylphosphonate (DMMP) is a simple organophosphate used industrially as a flame retardant and to lower viscosity in polyester and epoxy resins. The military considered the use of DMMP as a nerve gas simulant. Since military use of DMMP involved exposure by inhalation, there was a need for a subchronic inhalation exposure to DMMP to fully investigate its toxic potential.Male Fischer-344 rats were exposed to 25 ppm or 250 ppm DMMP vapor on a continuous basis for 90 days. An equal number of control rats were sham-exposed. Following the 90-day continuous exposure period, 15 male rats were sacrificed from each group. Two rats from each group had the left kidney perfused for electron microscopic examination. The kidneys were perfused from a height of 150 cm water with 1% glutaraldehyde in Sorensen's 0.1M phosphate buffer pH 7.2. An additional kidney was taken from a rat in each group and fixed by immersion in 2.5% glutaraldehyde and 2% paraformaldehyde in 0.1M cacodylate buffer pH 7.4. A portion of the 9 kidneys collected for electron microscopy were processed into Epon 812. Thin sections, stained with uranyl acetate and lead citrate, were examined with a JEOL 100B Transmission Electron Microscope. Microvilli height was measured on photographs of the cells of proximal tubules. This data, along with morphologic features of the cells, allows the proximal convoluted tubules (PCT) to be identified as being S1, S2, or S3 segment PCT.

Results of Chronic Dietary Toxicity Studies of High Viscosity (P70H and P100H) White Mineral Oils in Fischer 344 Rats

2004 ◽  
Vol 32 (4) ◽  
pp. 439-447 ◽  
Author(s):  
Gary W. Trimmer ◽  
James J. Freeman ◽  
R. A. J. Priston ◽  
Jan Urbanus
Keyword(s):  
High Viscosity ◽  
Female Rats ◽  
Fischer 344 Rats ◽  
Mesenteric Lymph Nodes ◽  
Mineral Oils ◽  
Fischer 344 ◽  
Mesenteric Lymph ◽  
Dietary Concentration ◽  
Study Results ◽  
White Mineral

Two-year dietary studies were conducted to determine the chronic toxicity and its reversibility, and the carcinogenicity of P70(H) and P100(H) white mineral oils in Fischer-344 rats (F-344). The studies were identical in design and followed the Organization for Economic Cooperation and Development, Guidelines for Testing Chemicals, Guideline 453, 1981. Additional endpoints evaluated were: (1) extent of mineral hydrocarbon deposition in liver, kidneys, mesenteric lymph nodes, and spleen of female rats at 3, 6, 12, 18 and 24 months, and (2) reversibility of effects following cessation of exposure. Dietary concentration were 60, 120, 240, and 1, 200 mg/kg/day, adjusted periodically to account for bodyweight changes. Study results were consistent with preceding subchronic studies. No treatment-related mortality, neoplastic lesions, or changes in clinical health, hematology, serum chemistry, or urine chemistry were evident in any group administered either white oil. Statistically significant higher food consumption was noted in the 1, 200 mg/kg group males and females exposed to either white oil and statistically significant higher body weights were noted in the 1, 200-mg/kg males during the latter portion of the P100(H) study. Higher mesenteric lymph node weights were accompanied by increased severity of infiltrating histiocytes. This occurred to a greater extent with the P70(H) than the P100(H) oil. No other histopathology of significance was observed. Mineral hydrocarbons were detected in the liver following exposure to either oil. Maximal concentrations of mineral hydrocarbons in the liver were similar with both oils but occurred more rapidly with the P70(H) oil. Liver mineral hydrocarbon content returned to near-background levels during the reversibility phase. In conclusion, lifetime exposer of F344 rats to P70(H) and P100(H) white oils resulted in only minimal findings and with no consequence to clinical health. Thus, under the conditions of these studies, the No Observable Adverse Effect Level (NOAEL) for these studies was considered to be 1, 200 mg/kg/day.

scholarly journals Do spermathecal morphology and inter-mating interval influence paternity in the polyandrous beetle Tribolium castaneum?

Behaviour ◽  
2006 ◽  
Vol 143 (5) ◽  
pp. 643-658 ◽  
Author(s):  
Ludovic Arnaud ◽  
Giorgina Bernasconi ◽  
Yves Brostaux ◽  
Eric P. Meyer
Keyword(s):  
Sperm Competition ◽  
Tribolium Castaneum ◽  
Reproductive Tract ◽  
Sperm Storage ◽  
Female Reproductive Tract ◽  
Phenotypic Marker ◽  
Male And Female ◽  
The Difference ◽  
Different Strains

AbstractIn polyandrous insects, postcopulatory sexual selection is a pervasive evolutionary force favouring male and female traits that allow control of offspring paternity. Males may influence paternity through adaptations for sperm competition, and females through adaptations facilitating cryptic female choice. Yet, the mechanisms are often complex, involving behaviour, physiology or morphology, and they are difficult to identify. In red flour beetles (Tribolium castaneum), paternity varies widely, and evidence suggests that both male and female traits influence the outcome of sperm competition. To test the role of spermathecal morphology and of sperm storage processes on the outcome of sperm competition, we mated each of 26 virgin females with two males, one of which carrying a phenotypic marker to assign offspring paternity. We manipulated the interval between mating with the first and the second male, to create different conditions of sperm storage (overlapping and non-overlapping) in the female reproductive tract. To investigate the role of sperm storage more closely, we examined the relationship between paternity and spermathecal morphology in a subset of 14 experimental females. In addition, we also characterized variation in spermathecal morphology in three different strains, wildtype, Chicago black and Reindeer. No significant influence of the intermating interval was found on the paternity of the focal male, although the direction of the difference was in the expected direction of higher last male paternity for longer intervals. Moreover, paternity was not significantly associated with spermathecal morphology, although spermathecal volume, complexity, and tubule width varied significantly and substantially among individuals in all investigated strains.

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