Biomedical subjects

M B Thompson

Publications and source records attributed to M B Thompson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Comparison of nutrient transport across the placenta of lizards differing in placental complexity.

We have reviewed published and new quantitative data on the net uptake of nutrients by embryos of oviparous and viviparous lizards that vary in chorioallantoic placental complexity to better understand the evolution of complex placentae. We assessed net nutrient uptake during embryonic development by measuring the total dry mass, or the mass of separate nutrients, in the egg at about the time of ovulation and in the neonate. There is no significant difference in the fresh egg to neonate dry mass ratio of oviparous and viviparous species that have simple placentae, indicating that there is little, if any, net uptake of nutrients by viviparous species with simple chorioallantoic placentae. In contrast, there is significant uptake of dry matter and individual nutrients across the placenta of species with complex chorioallantoic placentae. Species of the genus Niveoscincus have a range of placentae and nutrient uptakes, even among populations of one species, suggesting that further studies among populations of single species are required. Data are available for relatively few clades, and all the data for the three most complex chorioallantoic placental types are derived from a single genus. Thus, further research on new genera of lizards is required to overcome the potentially confounding effects of phylogeny in our analyses.

Allantois↗

PubMed2000

Energy consumption by embryos of a viviparous lizard, Eulamprus tympanum, during development.

Energy consumption during development has been measured in many oviparous lizards, but not in viviparous lizards in utero. It has always been assumed that energy consumption by embryos of viviparous lizards during development is similar to that of oviparous species. Estimation of energy consumption of viviparous lizards in vivo are confounded by the possible influence of pregnancy on maternal metabolism. Here we separated maternal and embryonic metabolism in measurements of pregnant Eulamprus tympanum throughout pregnancy. Our data support the hypothesis that the energetic cost of development in viviparous lizards (19.8 kJ g(-1)) is similar to that in oviparous lizards (mean 16.2 kJ g(-1)), at least for a species with a simple placenta. An increase in maternal metabolism of 29% above that for non-pregnant E. tympanum goes to maintain pregnancy, and represents an important component of the reproductive effort in E. tympanum.

Animals↗

PubMed1999

Epidermal differentiation in the developing scales of embryos of the Australian scincid lizard Lampropholis guichenoti.

Formation of the first epidermal layers in the embryonic scales of the lizard Lampropholis guichenoti was studied by optical and electron microscopy. Morphogenesis of embryonic scales is similar to the general process in lizards, with well-developed overlapping scales being differentiated before hatching. The narrow outer peridermis is torn and partially lost during scale morphogenesis. A second layer, probably homologous to the inner peridermis of other lizard species, but specialized to produce lipid-like material, develops beneath the outer peridermis. Two or three lipogenic layers of this type develop in the forming outer surface of scales near to the hinge region. These layers form a structure here termed "sebaceous-like secretory cells." These cells secrete lipid-like material into the interscale space so that the whole epidermis is eventually coated with it. This lipid-like material may help to reduce friction and to reduce accumulation of dirt between adjacent extremely overlapping scales. At the end of their differentiation, the modified inner periderm turns into extremely thin cornified cells. The layer beneath the inner peridermis is granulated due to the accumulation of keratohyalin-like granules, and forms a shedding complex with the oberhautchen, which develops beneath. Typically tilted spinulae of the oberhautchen are formed by the aggregation of tonofilaments into characteristically pointed cytoplasmic outgrowths. Initially, there is little accumulation of beta-keratin packets in these cells. During differentiation, the oberhautchen layer merges with cells of the beta-keratin layer produced underneath, so that a typical syncytial beta-keratin layer is eventually formed before hatching. Between one-fourth distal and the scale tip, the dermis under epidermal cells is scarce or absent so that the mature scale tip is made of a solid rod of beta-keratinized cells. At the time of hatching, differentiation of a mesos layer is well advanced, and the epidermal histology of scales corresponds to Stage 5 of an adult shedding cycle. The present study confirms that the embryonic sequence of epidermal stratification observed in other species is basically maintained in L. guichenoti.

Animals↗

PubMed1999

Cyclosporin A attenuates acute mitochondrial dysfunction following traumatic brain injury.

Experimental traumatic brain injury (TBI) results in a rapid and significant necrosis of cortical tissue at the site of injury. In the ensuring hours and days, secondary injury exacerbates the primary damage, resulting in significant neurological dysfunction. Recent reports from our lab and others have demonstrated that the immunosuppressant cyclosporin A (CsA) is neuroprotective following TBI. The opening of the mitochondrial permeability transition pore (MPTP) is inhibited by CsA, thereby maintaining the mitochondrial membrane potential and calcium homeostasis in isolated mitochondrial. In the present study we utilized a unilateral controlled cortical impact model of TBI to assess mitochondrial dysfunction in both isolated mitochondria and synaptosomes to elucidate the neuroprotective role of CsA. The results demonstrate that administration of CsA 15 min postinjury significantly attenuates mitochondrial dysfunction as measured using several biochemical assays of mitochondria integrity and energetics. Following TBI, mitochondria isolated from the injured cortex of animals treated with CsA demonstrate a significant increase in mitochondria membrane potential and are resistant to the induction of mitochondrial permeability transition compared to vehicle-treated animals. Similarly, synaptosomes isolated from CsA-treated animals demonstrate a significant increase in mitochondria membrane potential, accompanied by lower levels of intramitochondrial Ca2+ and reactive oxygen species production than seen in vehicle-treated animals. These results suggest that the neuroprotective properties of CsA are mediated through modulation of the MPTP and maintenance of mitochondria homeostasis. Amelioration of cortical damage with CsA indicates that pharmacological therapies can be devised which will significantly alter neurological outcome after injury.

Animals↗

PubMed1999

Lipid composition of eggs of an oviparous lizard (Bassiana duperreyi).

Lipid analysis was performed on freshly ovulated eggs (n = 5) of the oviparous lizard Bassiana duperreyi. The fresh weight of the whole egg contents was 132.0 +/- 4.3 mg (mean +/- SE) of which lipid constituted 21.9 +/- 1.1% (w/w). Triacylglycerol formed an exceptionally high proportion (85.4 +/-0.5%, w/w) of the total lipid, whereas phospholipid, free cholesterol, cholesteryl ester, and free fatty acid, respectively, contributed 11.2 +/- 0.3, 1.4 +/- 0.1, 1.3 +/- 0.1, and 0.6 +/- 0.1% of the total lipid mass. Linoleic and alpha-linolenic acids were the major polyunsaturates of the triacylglycerol fraction, respectively, forming 16.3 +/- 0.1 and 8.3 +/- 0.1% (w/w) of the fatty acids. Linoleic acid was the major fatty acid (29.0 +/- 0.1%) of the total phospholipid, which also contained substantial amounts of arachidonic (6.4 +/- 0.1%) and eicosapentaenoic (3.0 +/- 0.1%) acids, but a relatively low proportion (1.6 +/- 0.1%) of docosahexaenoic acid. Phosphatidylcholine formed the major phospholipid class (73.8 +/- 2.3%) w/w of total phospholipid) and was enriched in linoleic acid, whereas phosphatidylethanolamine, which formed 20.4 +/- 1.9%(w/w) of total phospholipid, contained higher proportions of arachidonic and docosahexaenoic acids.

Animals↗

PubMed1999

Epidermal differentiation during carapace and plastron formation in the embryonic turtle Emydura macquarii.

As part of a large comparative study on the development of reptilian skin, we provide the first ultrastructural description of differentiation of the epidermis of the carapace and plastron in the Chelonia, using the Australian pleurodiran turtle Emydura macquarii as a model. The epidermis is initially composed of an external flat peridermis and a basal layer of cuboidal cells. During differentiation, the peridermis darkens, flakes off and is partially lost before hatching. Four to 6 layers of flat cells containing lipids and mucus form from the basal layer beneath the external peridermis. Because such cells are found only during embryogenesis, we have referred to these layers as embryonic epidermis. They contain reticulate bodies made of a meshwork of coarse filaments similar to those described in the inner peridermis of lizard and bird embryos. In advanced embryos, cells of the embryonic epidermis condense into a thin dark stratum which is subsequently lost after hatching. The lowermost 2 layers of the embryonic epidermis keratinise, as for a typical lepidosaurian alpha-layer. A splitting zone is progressively formed beneath the alpha-layer to separate the embryonic epidermis from the underlying beta-layer. Patterns of cytodifferentiation of the beta-synthesising cells over the carapace and plastron essentially resemble those of the lepidosaurian epidermis. The beta-keratin matrix initially accumulates among ribosomes as round bodies not clearly surrounded by a membrane. These bodies appear not to be derived from the Golgi apparatus. Melanosomes and other dark granules of uncertain nature are present among early differentiating beta-cells. The round beta-keratin bodies merge with the dense bodies to produce the definitive variegated pattern of the mature beta-keratin layer. The histochemistry suggests that calcium combines with organic molecules within beta-keratinising cells to harden the tissue. In contrast to the beta-keratin cells of lizards and snakes, cells of the mature beta-keratin layer of E. macquarii maintain their cell boundaries in part or completely, a characteristics shared with the beta-keratin layer of Sphenodon and crocodilians.

Animals↗

PubMed1998

The diet and digestive energetics of an Australian short-necked turtle, Emydura macquarii.

We described the diet of Emydura macquarii, an omnivorous turtle from south-eastern Australia, compared its digestive performance on diets of fish or plants at two temperatures, and related how both diet and temperature affect its food selection in nature. Filamentous algae constituted 61% of the stomach content of E. macquarii. The turtles rarely fed on motile prey, but selected carrion from the lagoon bottom and terrestrial insects (Diptera, Hymenoptera and Coleoptera) trapped on the surface of the water. Digestive efficiency of E. macquarii was affected little by body temperature, in contrast to consumption rates and rates of passage which were strongly influenced by both temperature and diet. In combination, these responses resulted in a slower rate of digestion at 20 degrees C than at 30 degrees C. Digestive efficiency of E. macquarii on a herbivorous diet at 30 degrees C (49%) was about half that of turtles on a carnivorous diet (91%), but they had longer transit times (118 h on the plant diet versus 70 h). Lower consumption rates and longer mean retention times in turtles fed plants compared those fed fish relate to slower digestive processing of the plant. Rapid processing and higher consumption rates of fish by E. macquarii resulted in higher energy gains compared to turtles consuming plants (almost 100 times more energy at 30 degrees C). The laboratory results suggest that fish carrion and aquatic and terrestrial invertebrates are probably essential dietary items of E. macquarii in the wild, because its metabolic requirements cannot be met from aquatic macrophytes alone.

Animals↗

PubMed1996

Frequency and relationships of clinical chemistry and liver and kidney histopathology findings in 13-week toxicity studies in rats.

The relative sensitivities of eight commonly used clinical chemistry end points and histopathology to detect potential toxic effects in liver and kidney were evaluated for a series of 61 13-week rat toxicity studies conducted for the National Toxicology Program. The data consisted of 1-,2- to 3-, and 13 week clinical chemistry measurements and 13-week histopathological assessments of liver and kidney. Except for serum alkaline phosphatase, treatment-related alterations of individual clinical chemistry variables occurred in 20-48% of the studies, depending on the analyte, sampling time, and sex. Liver and kidney lesions were reported for 31% and 41% of the studies respectively. There was an association between treatment-related increases in alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities and histopathological changes in the liver. SDH activity had greater positive and negative predictive values than similar changes in ALT; by week 1 in females and weeks 2-3 in both sexes. SDH predicted morphological hepatic change at study termination with 75% or better accuracy. If increases in activities of both enzymes occurred simultaneously, however, terminal histopathological changes could be predicted, in both sexes, with 75% accuracy by week 1, increasing to 100% by weeks 2-3. There also was an association between treatment-related increases in urea nitrogen (UN) and creatinine (Cre) concentrations and morphological kidney change. Cre concentration had greater positive predictive values than similar changes in UN; by weeks 2-3 in males and week 13 in both sexes. Cre predicted morphological renal change at study termination with 56% or better accuracy. UN concentration was associated and predictive of morphological kidney change only in females at week 13. Depending on time point and sex, serum alkaline phosphatase activity increased in 5-22% of the studies. Increases in total bile acid concentration occurred in 33-48% of the studies. Because both tests are used as markers of cholestasis, this marked discrepancy was unexpected. Treatment-related decreases in alkaline phosphatase activity occurred, however, in 39-56% of the studies; serum alkaline phosphatase may be more useful as an indicator of decreased food intake (decreased activity) than of cholestasis (increased activity). In summary, treatment-related alterations of clinical chemistry and histopathology occurred frequently in this series of toxicity studies in rats. Changes in the chemistry end points also occurred frequently at interim time points, indicating that clinical chemistry evaluations can be useful for detecting potential treatment effects throughout a study. This observation is important, since histopathological evaluations are limited to animal termination and not useful for detecting transient responses or the onset of treatment-related effects.

Alanine Transaminase↗

PubMed1996

Effects of oral ursodeoxycholic acid in healthy cats on clinicopathological parameters, serum bile acids and light microscopic and ultrastructural features of the liver.

A blind, placebo-controlled study evaluated the effects of ursodeoxycholic acid (UDCA) given orally, at a dose of 15 mg kg-1 per day for eight weeks, on the physical condition, haematological and serum biochemical profiles, urinalysis, total serum bile acids (TSBA) and hepatic histology of four healthy cats. There were no clinically important significant differences between the groups or within the treatment groups in clinicopathological parameters. TSBA concentrations or histology. A significant lower concentration/proportion of taurochenodeoxycholic acid was observed in the treated cats (P = 0.05). Only one treated cat accumulated measurable quantities of UDCA, and the compound appeared to be non-toxic. It did not increase the concentration of TSBA, and accumulated minimally in the serum. It should be investigated for therapeutic use in cats with hepatobiliary disease.

Administration, Oral↗

PubMed1994

Toxicology studies of a chemical mixture of 25 groundwater contaminants: hepatic and renal assessment, response to carbon tetrachloride challenge, and influence of treatment-induced water restriction.

Because groundwater contamination is an important environmental concern, we examined the hepatic and renal effects of repeated exposure to a mixture of 25 chemicals frequently found in groundwater near hazardous-waste disposal sites and the effect of such exposure on carbon tetrachloride (CCI4) toxicity. Adult male F-344 rats received ad libitum deionized water and feed (Ad Lib Water) or ad libitum 10% MIX (referring to 10% of a technically achievable stock mixture) and feed for 14 d. Because exposure to the 25-chemical mixture via the drinking water resulted in decreased water and feed consumption, restricted deionized water and feed controls (Restricted Water) were included. On d 14, rats were gavaged with 0, 0.0375, 0.05, 0.075 or 0.15 ml CCl4/kg, and hepatic and renal toxicity assessed 24 h later. Little or no hepatic and renal toxicity was observed in rats exposed to 10% MIX alone. No hepatic or renal lesions occurred that could be attributed to 10% MIX alone. Slight but statistically significant alterations, of uncertain biological significance, resulted from the water treatments: 10% MIX increased alanine aminotransferase, urea nitrogen (BUN), and BUN/creatinine ratio; Restricted Water increased 5'-nucleotidase and decreased alkaline phosphatase. Relative kidney weight was increased by both 10% MIX and Restricted Water. CCI4 resulted in significant dosage-dependent hepatotoxicity in all three water treatment groups but had little or no effect on renal indicators of toxicity. Relative to Ad Lib Water, significantly greater hepatotoxicity occurred in both 10% MIX and Restricted Water rats. The response to CCI4 in the Restricted Water rats was similar to that of 10% MIX rats, indicating that a substantial portion of the effect of 10% MIX on CCI4 hepatotoxicity is due to decreased water and feed intake.

Analysis of Variance↗

PubMed1994

The effects of guided imagery on anxiety levels and movement of clients undergoing magnetic resonance imaging.

This randomized, experimental study examined the effects of guided imagery on anxiety levels and on movement of clients undergoing nonemergency magnetic resonance imaging (MRI). Subjects who listened to a guided imagery/relaxation tape (n = 20) before their MRI scan and used guided imagery during their scan had lower levels of state anxiety than the control group (n = 21). Based on subject report and operator report, the experimental group moved less frequently during the MRI than the control group. The results of this investigation support the use of guided imagery as a therapeutic intervention and Rogers' Science of Unitary Human Beings.

Adolescent↗

PubMed1994

Heterothermy, torpor, respiratory gas exchange, water balance and the effect of feeding in Gould's long-eared bat Nyctophilus gouldi.

The effects of temperature and nutritional status on the metabolic rate of Nyctophilus gouldi were examined. Bats fed marked meals first defecated approximately 1.34 h after feeding and were calculated to have a mean retention time of 5.38 +/- 0.57 h but to be truly post-absorptive after 9 h. Over the temperature range 1-35 degrees C, the metabolic rate (Vo2) and body temperature (Tb) of fasted bats were extremely labile. Below 30 degrees C, the bats all entered torpor and between 10 and 15 degrees C showed a mean 84% reduction over the maximal Vo2. Body temperature was also minimal over this range (Tb = 12.5 degrees C, Ta = 10-15 degrees C). Both total and dry thermal conductance increased in a curvilinear manner with temperature, total conductance from 3.38 +/- 0.65 J g-1 h-1 degree C-1 at 1 degree C to 24.25 +/- 1.99 J g-1 h-1 degree C-1 at 35 degrees C (mean +/- S.E.M.), while the rate of evaporative water loss increased with Ta by a maximum of 10-fold from 0.21 mg g-1 h-1 at 5 degrees C to 2.69 mg g-1h-1 at 35 degrees C. Between 10 and 25 degrees C, intermittent respiration characterised by episodic bouts of breathing/gas exchange and periods of apnoea with no measurable Vo2 occurred. Although the duration of apnoea decreased when temperature was increased, the volume of oxygen taken up in each episode did not change. Mean respiratory exchange ratio (RER) was low (0.64-0.77) in post-absorptive bats, typical of fat utilisation, but during torpor ranged from near 0 to near 2, indicating discontinuous and disproportional gas exchange. Feeding produced a condition of relatively sustained homeothermy and high RER in the bats which persisted for 9 h, after which the N. gouldi became torpid. Immediately after feeding, the Vo2 of the bats increased fivefold above the post-absorptive level, while the Vco2 increased by more than eightfold. Similarly, body temperature also increased, declining to torpid values after 9. The RER in immediately post-feeding bats was near 1.0 but subsequently declined to near 0.7, indicating a switch from carbohydrate to fat utilisation. Therefore, the N. gouldi were heterothermic, exhibited a highly labile metabolic rate, and rates of heat and water loss, and Tb which were influenced both by ambient temperature and by nutritional status.

Animal Feed↗

PubMed1993

Nuclear magnetic resonance identification of the taurine conjugate of 3 alpha,6 beta,7 beta-trihydroxy-5 beta,22-cholen-24-oic acid (tauro-delta 22-beta-muricholate) in the serum of female rats treated with alpha-naphthylisothiocyanate.

Recently developed 1H nuclear magnetic resonance methods, including 2-dimensional, 1H-detected-[13C] shift correlation spectroscopy and 1-dimensional HOHAHA spectroscopy at 500 MHz have been used to identify the major bile acid in the serum of rats treated with alpha-naphthylisothiocyanate as the taurine conjugate of 3 alpha,6 beta,7 beta-trihydroxy-5 beta,22-cholen- 24-oic acid (tauro-delta 22-beta-muricholate), a derivative of beta-muricholate having an unsaturated bond in the acyclic side chain. Complete stereospecific assignments of the 1H and protonated 13C spectra of the title compound and beta-muricholate are reported. The assignments were based entirely on 1H-1H and 1H-13C scalar connectivities and were made using approximately 0.5-2.0 mg of material. It is suggested that these new methods will be of general value for identifying the structure and assigning the spectra of other scarce steroid-like molecules.

1-Naphthylisothiocyanate↗

PubMed1993

Taurine conjugate of 3 alpha,6 beta,7 beta-trihydroxy-5 beta,22-cholen-24-oic acid (tauro-delta 22-beta-muricholate): the major bile acid in the serum of female rats treated with alpha-naphthylisothiocyanate and its secretion by liver slices.

The taurine conjugate of 3 alpha,6 beta,7 beta-trihydroxy-5 beta,22-cholen-24-oic acid (tauro-delta 22-beta-muricholate) has been identified in the serum of female rats treated with alpha-naphthylisothiocyanate. Using a high performance liquid chromatographic/enzymatic method for measurement of bile acids, tauro-delta 22-beta-muricholate was the predominant bile acid in the serum of female Fischer 344 rats treated for 3 days with alpha-naphthylisothiocyanate. Other significant changes in concentrations of serum bile acids included increases in tauro-alpha-muricholate, tauro-beta-muricholate, taurocholate, taurochenodeoxycholate, and several unknown bile acids. The formation of tauro-delta 22-beta-muricholate was examined in vitro using liver slices from control rats and rats treated with alpha-naphthylisothiocyanate. Slices were incubated for 7 h in William's E medium containing no bile acids or 25 mumol/l of one of the following: beta-muricholate, tauro-beta-muricholate, or cholate. Tauro-delta 22-beta-muricholate was secreted by slices from control and treated rats and the rate was increased significantly by the addition of beta-muricholate (2.9-5.6-fold) but not tauro-beta-muricholate or cholate to the medium. Tauro-delta-beta-muricholate was formed by liver slices from endogenous precursors and from exogenous beta-muricholate. Pretreatment of rats with alpha-naphthylisothiocyanate did not alter total secretion rates but those of some important individual bile acids were affected. Because of the increased secretion of tauro-delta-beta-muricholate by liver slices with the addition of beta-muricholate to the medium, the liver may be the primary site of formation for this unsaturated bile acid.

1-Naphthylisothiocyanate↗

PubMed1992

Application of molecular encapsulation for toxicology studies: comparative toxicity of p-Chloro-alpha, alpha, alpha-trifluorotoluene in alpha-cyclodextrin vehicle versus corn oil vehicle in male and female Fischer 344 rats and B6C3F1 mice.

The application of alpha-cyclodextrin (alpha-CD) as an alternative vehicle for water insoluble and volatile chemicals was investigated in toxicity studies of p-chloro-alpha, alpha, alpha-trifluorotoluene (CTFT). Groups of F344 rats and B6C3F1 mice of each sex were administered CTFT (97% pure) by gavage in either corn oil or alpha-CD aqueous formulations daily for 14 consecutive days. The dose levels used were 10 (mice only), 50, 400, and 1000 mg/kg for corn oil vehicle and 10, 50, and 400 mg/kg (maximum achievable dose at gavage volume of 5 ml/kg) for alpha-CD vehicle. With both vehicles CTFT and alpha 2u-globulin were found to accumulate in the male rat kidney after 14 days of exposure and a dose-related toxic nephropathy was observed at dose of 50 mg/kg or higher. The hepatocellular hypertrophy and cytoplasmic vacuolation of the adrenal cortex which appeared in dosed male and female rats were also found to be independent of vehicle. Clinical pathology findings suggested a mild anemia and cholestasis in rats. With both vehicles no tissue bioaccumulation of CTFT was found in male or female mice. Vehicle-independent hepatocellular hypertrophy and cholestasis were also observed in mice at doses of 400 and 1000 mg/kg. In conclusion, the alpha-CD vehicle does not affect the toxic responses of CTFT in both sexes of both species. The results of the studies suggest that alpha-CD may be an appropriate alternative vehicle for toxicity studies.

Alpha-Globulins↗

PubMed1992

Subchronic (13-week) toxicity studies of oral phenolphthalein in Fischer 344 rats and B6C3F1 mice.

Phenolphthalein is a cathartic agent that is widely used in over-the-counter laxatives. Thirteen-week toxicity studies of phenolphthalein were performed using F344/N rats and B6C3F1 mice. Rats and mice were fed ad libitum with a NIH 07 diet containing 0; 3000; 6000; 12,000; 25,000; or 50,000 ppm phenolphthalein. On a milligram per kilogram body weight basis, rats and mice fed 50,000 ppm phenolphthalein ingested more drug than would be expected during human laxative abuse. Phenolphthalein produced little evidence of toxicity in rats. There was slightly lower weight gain among the 25,000 and 50,000 ppm groups. Treated rats showed elevated relative kidney weights (males only) and elevated absolute and relative liver weights at 12,000-50,000 ppm phenolphthalein. Rat serum bile acids were depressed early (Days 5 and 6) by phenolphthalein treatment. Several treatment-related toxic effects, however, were identified in mice who received more phenolphthalein per unit body weight than rats. Although there were no effects on body weight gain, elevated liver weights were noted in female mice receiving 6000-50,000 ppm phenolphthalein. The primary treatment-related findings that occurred during the mouse studies involved the reproductive and hematopoietic systems. Reproductive changes including depressed testis and right epididymal weights and sperm density, an elevated production of abnormal sperm, and morphologic alterations in seminiferous tubules occurred at all levels of exposure (3000-50,000 ppm). Hematopoietic changes included bone marrow hypoplasia (12,000-50,000 ppm), increased splenic hematopoiesis (males only; 25,000 and 50,000 ppm), and an elevated incidence of micronucleated erythrocytes (6000-50,000 ppm).

Animals↗

PubMed1992

Toxicity of monochloroacetic acid administered by gavage to F344 rats and B6C3F1 mice for up to 13 weeks.

Groups of 20 rats and 20 mice of each sex were administered monochloroacetic acid (MCAA) once daily, 5 days per week, in water by gavage for up to 13 weeks. Doses used were 0, 30, 60, 90, 120, or 150 mg/kg for rats and 0, 25, 50, 100, 150, or 200 mg/kg for mice. Compound-related deaths occurred at the four highest dose levels in rats and at the highest dose level in mice. Mean body weights of treated groups of rats and mice surviving until the end of the study were similar to those of the controls. A dose-related increase in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, as well as a dose-related increase in the relative liver and kidney weights was observed in rats but not in mice. A dose-related increase in the incidence and severity of cardiomyopathy occurred in rats. This lesion may be related to the inhibition of heart mitochondrial aconitase activity. No compound-related lesions were observed in mice. The results of this study indicate that F344 rats are more sensitive than B6C3F1 mice; sexes within the species were equally sensitive. The no-observable-effect level was estimated as 30 mg MCAA/kg body weight for rats and 100 mg MCAA/kg body weight for mice.

Acetates↗

PubMed1992

Clinical pathology in the National Toxicology Program.

The National Toxicology Program (NTP) developed a standard approach for clinical pathology investigations that was integrated into most toxicity studies designed and conducted after 1986. Protocols for these studies include specific hematology and clinical chemistry analyses at 3 selected time points in 13-wk studies. Requirements concerning the anesthetization of animals, collection and analysis of samples, and reporting of results have been established to control sources of variability within and between contract laboratories that perform these studies for the NTP. Laboratories must meet minimum standards to be approved for participation in the Program. Important areas of consideration for these laboratories to perform clinical pathology investigations include the facility, equipment, personnel, performance, and quality control procedures. Clinical pathology results from approximately 60 13-wk studies that have been conducted by the NTP in 7 laboratories since 1987 are being analyzed to generate a database of control values for the Fischer rat and B6C3F1 mouse and to identify sources of variability. Experimental data from these studies are being analyzed and correlated with histopathologic findings to evaluate the contribution of clinical pathology to the characterization of toxicity and to examine the appropriateness of the current approach. Efforts such as these will provide for the evolution and continued relevance of clinical pathology in toxicity testing.

Animals↗