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Biomedical subjects

R R Maronpot

Publications and source records attributed to R R Maronpot.

At least 163 records · Page 9Linked to original sources
PubMed1985

Ethyl acrylate-induced gastric toxicity. I. Effect of single and repetitive dosing.

Ethyl acrylate (EtAc) is widely used in the production of polymers and copolymers for use in the preparation of latex paints, textiles, paper coatings, and specialty plastics. EtAc caused squamous cell carcinomas and papillomas in the forestomach (nonglandular portion of the stomach) of both sexes of F344 rats and B6C3F1 mice when administered chronically by gavage. The current studies were undertaken to investigate and characterize the nature of the acute gastric toxicity caused by EtAc. Gavage administration of a single dose of 100, 200, or 400 mg/kg EtAc (in corn oil) to F344 male rats caused dose-and time-dependent mucosal and submucosal edema and vacuolization of the tunica muscularis in the forestomach and mild submucosal edema in the glandular stomach. Equivalent sc or ip doses did not produce similar gastric lesions. Treatment of rats with two or four consecutive oral daily doses (200 mg/kg each) of EtAc caused mucosal edema associated with vesicle formation, mucosal hyperplasia, submucosal edema and inflammation, and vacuolization of the tunica muscularis of the forestomach. Submucosal edema and inflammation were also observed in the glandular stomach and mucosal erosions or ulcers were observed in both portions of the stomach after repeated oral exposure to EtAc. The absence of systemic toxicity plus the dependency of gastric lesions on the gavage route of administration suggest that the EtAc-induced gastric lesions may be a consequence of localized hemodynamic changes, specifically those characteristic of a classical immediate inflammatory response to an injurious agent at the site of administration.

Acrylates↗
PubMed1985

Ethyl acrylate-induced gastric toxicity. II. Structure-toxicity relationships and mechanism.

Earlier studies conducted in this laboratory demonstrated that gavage administration of ethyl acrylate caused pronounced gastric toxicity in rats given single or repeated doses. The current studies were undertaken to investigate the structural, metabolic, and physical basis of this chemically induced gastric toxicity. Gavage administration of equimolar doses (2 mmol/kg) of methyl or ethyl acrylate in corn oil resulted in profound gastric toxicity in male F344 rats, while acrylic acid and n-butyl acrylate were without effect. Furthermore, gavage administration of equimolar doses of methyl propionate or ethyl propionate (saturated analogues of methyl acrylate and ethyl acrylate, respectively) as well as methacrylic acid esters were without gastric toxicity. These results indicate that structural requirements for acrylate esters to cause gastric lesions include an intact ester moiety, a double bond, and no substitution at carbon number 2. Additional studies indicate that gastric toxicity may be attributed to the intact ester molecule or to metabolite(s) other than products of carboxylesterase-mediated hydrolysis (acrylic acid and alcohol) and that gastric toxicity is dependent upon both acrylate ester concentration in dose vehicle and the lipophilicity of the dose vehicle (corn oil vs water).

Acrylates↗
PubMed1985

Adverse effects of butyl benzyl phthalate on the reproductive and hematopoietic systems of male rats.

A 14-day dietary study was conducted in adult, male, Fischer 344 rats at levels of 0.0, 0.625, 1.25, 2.5 and 5.0% butyl benzyl phthalate (BBP) to evaluate potential effects of this plasticizer on the male reproductive and hematopoietic systems. Total body, thymus, testis, epididymis, prostate and seminal vesicle weights were reduced in the 2.5% and 5% BBP dose groups, while pituitary weight was unaffected. Histological evaluations revealed dose-dependent atrophy of the testis, prostate and seminal vesicles at 2.5% and 5%, atrophy of the thymus and epididymis at 5%, and the presence of immature sperm cells in the tubular lumens and necrosis of the tubular epithelium in the epididymis at 2.5% and 5% BBP. Plasma testosterone concentration was decreased at 5%, while follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were increased at 2.5% and 5.0% BBP. The circulating components of blood, and clotting times (prothrombin time, activated partial thromboplastin time), were unaffected although bone marrow cellularity was reduced at 2.5% and 5%. Changes in non-reproductive organs included enlargement of liver and kidneys, thymic atrophy and associated morphological abnormalities in these organs. These data indicate a direct toxic effect of BBP on the testis with secondary effects on other reproductive organs. Pituitary and hypothalamic responses did not appear to be affected. The reduced bone marrow cellularities suggest that prolonged exposures to BBP could affect circulating blood components or compromise clotting ability.

Animals↗
PubMed1985

Reproductive and developmental toxicity of ethylene glycol in the mouse.

The effects of ethylene glycol on reproduction of CD-1 mice were tested in a protocol which permitted continuous breeding during a specified interval. The dosage amounts of 0, 0.25, 0.5, or 1% ethylene glycol by continuous administration in drinking water for male and female mice were selected from the general toxic responses observed in a 14-day pilot study. After the first week of administration, begun at 11 weeks of age, the animals were housed one male and one female per cage for 14 weeks during which time any offspring were examined, sexed, weighted, and killed to allow continuous mating of the first generation. At the end of the 14-week cohabitation period, the males and females were separated and any litters delivered after that time were kept until weaning. Those second-generation animals were mated at about 70 days of age. Slight, but statistically significant, decreases were found in the numbers of litters per fertile pair and live pups per litter in the 1% dose group and live pup weight at the 1% dose groups compared to control F0 mice. Facial anomalies were noted in a number of offspring of high-dose-treated mice and an examination for skeletal defects demonstrated a pattern including reduction in the size of bones in the skull, fused ribs, and abnormally shaped sternebrae and vertebrae in the high-dose-treated, but not the untreated, mice. Neither the 0.25 nor 0.5% dose groups were significantly affected. No clinical signs of toxicity or significant adverse effects on body weight or water consumption were seen at the doses used, but two deaths occurred at the 0.5% quantity which may have been related to oxalate crystal deposition in the kidney.

Animals↗
PubMed1985

Dermal oncogenicity bioassays of monofunctional and multifunctional acrylates and acrylate-based oligomers.

Several important components of photocurable coatings were studied for dermal tumorigenic activity by repeated application to the skin of mice. The substances tested were 2-ethylhexyl acrylate (EHA) and methylcarbamoyloxyethyl acrylate (MCEA) (monomers); neopentyl glycol diacrylate (NPGDA), esterdiol-204-diacrylate (EDDA), and pentaerythritol tri(tetra)acrylate (PETA) (cross-linkers); and three acrylated urethane oligomers. For each bioassay, 40 C3H/HeJ male mice were dosed 3 times weekly on the dorsal skin for their lifetime with the highest dose of the test agent that caused no local irritation or reduction in body weight gain. Two negative control groups received acetone (diluent) only. A positive control group received 0.2% methylcholanthrene (MC). NPGDA and EHA had significant tumorigenic activity with tumor yields of eight and six tumor-bearing mice (three and two malignancies), respectively. The MC group had 34 mice with carcinomas and 1 additional mouse with a papilloma. MCEA had no dermal tumorigenic activity but resulted in early mortality. No skin tumors in the treatment area were observed in the other groups. Additional studies will be necessary to elucidate possible relationships between structure and tumorigenic activity for the acrylates.

Acrylates↗
PubMed1985

Variations in the histologic distribution of rat bone marrow cells with respect to age and anatomic site.

Bone marrow cellularity in untreated Fischer 344/N rats was subjectively evaluated in hematoxylin and eosin (H & E)-stained histologic sections from femur, tibia, humerus, sternum, lumbar vertebrae, ribs, pelvis, and skull of 2-, 4-, 7-, 16-, and 24-month-old males. Marrow cellularity varied with age of the rat and bone site sampled. Hematopoietic cellularity was consistently higher in rats less than 4 months of age and less consistently higher in 24-month-old rats versus intermediate age groups examined. The 24-month-old rats had the greatest animal-to-animal variation in cellularity. Site differences in bone marrow cellularity were present and similar at 4, 7, and 16 months. Mean percentage of marrow space occupied by hematopoietic cells ranged from 33-75%. Categories for histologic grading of bone marrow cellularity are presented. Sternum, femur, and humerus are recommended sites for histologic evaluation of bone marrow cellularity from conventional H & E-stained sections. Definitive evaluation and assessment of hematopoietic perturbations should not be solely based on subjective evaluation of routine histologic sections.

Aging↗
PubMed1985

Brain tumors in F344 rats associated with chronic inhalation exposure to ethylene oxide.

Groups of F344 rats of each sex were exposed to either ethylene oxide (ETO) vapor (concentrations of 100, 33 or 10 ppm) or to room air for 6 hours daily, 5 days per week, for up to 2 years. Three representative sections of the brain from each rat were evaluated. Twenty-three primary brain tumors were found, two of which were in control animals. Increased numbers of brain tumors were seen in 100 ppm and 33 ppm ETO exposed male and female rats. Significant trend analyses were found for both males and females, indicating that, under the conditions of this study, ETO exposure above 10 ppm was related to the development of these brain tumors.

Air Pollutants↗
PubMed1985

Comparison of the morphology and enzyme activity of mononuclear cells from Fischer 344 rats with either spontaneous or transplanted leukemia.

Mononuclear cell (MNC) leukemia was identified in 26-month-old F344 rats by splenomegaly, reduced red blood cell counts, and elevated white blood cell counts. Atypical MNC were predominant in spleen and blood with acentric nuclei and red cytoplasmic granules. Pentose shunt, glycolytic, and Krebs cycle enzyme activities were elevated 2- to 11-fold in the enriched MNC fraction (Ficoll-Paque density gradients, 1.077 g/ml) isolated from spleen. A leukemic MNC line was derived from one of the spontaneously leukemic donors and then maintained in vivo by s.c. transfer of 2 X 10(7) spleen cells into 7-8-week-old syngeneic recipients. In these serial transplantation experiments leukemia that was clinically and morphologically indistinguishable from spontaneous leukemia in 104-week-old rats was induced in 22-24-week-old rats. Enhanced enzyme activity in MNC was not essential to maintain the phenotypic expression of Fischer rat leukemia. The pattern of biochemical response in spleen MNC from transplanted cases was the opposite of that previously noted in spontaneously leukemic rats, with 50-70% decreases in the specific activities of pentose shunt enzymes and malate dehydrogenase. Reversal of the expression of these enzymes in MNC may be related to a difference in the growth rate of the tumors or to selective proliferation of the transplanted leukemic cells. In addition acetylcholinesterase activity decreased 35-85% in MNC of spleen and blood. Transplantable MNC from F344 rats provide abundant tumorigenic material with a novel biochemical expression that may be useful in the study of chemotherapeutic intervention.

Acetylcholinesterase↗
PubMed1984

A two-year inhalation study of the carcinogenic potential of ethylene oxide in Fischer 344 rats.

Fischer 344 rats were exposed to 100, 33, 10, or 0 ppm of ethylene oxide vapor (EtO) by inhalation for 6 hr per day, 5 days per week, for approximately 2 years. Inhalation of EtO resulted in a significant depression of body weight gain in the 100- and 33-ppm exposure groups and a significant increase in mortality in the 100-ppm group. Through 18 months of exposure to EtO, no statistically significant increases in tumor incidence were observed. After 18 months, the incidence of primary brain tumors was increased for both sexes. Statistical evaluation indicated a treatment-related response, particularly for the male rats, in the 100- and 33-ppm exposure groups. After 24 months of exposure, histologic findings confirmed hematologic evidence that exposure to EtO resulted in an increased prevalence of mononuclear cell leukemia, which is a neoplasm that is common in aged Fischer 344 rats. This increase was dose related and increased for each of the three exposure concentrations. The percentage of female rats with multiple neoplasms was also greater in all three exposure groups than in controls. Furthermore, in both the 100- and 33-ppm exposure groups, the percentage of female rats with at least one malignant neoplasm was increased. An increased frequency of peritoneal mesothelioma was treatment related in the male rats exposed to 100 or 33 ppm of EtO. This study has shown biologically significant adverse effects at all concentrations tested. The incidences of mononuclear cell leukemia, peritoneal mesothelioma, and primary brain tumors in the air-control rats were similar to those reported in the literature. The possible contribution of a sialodacryoadenitis viral outbreak (which occurred during the 15th exposure month) to the EtO exposure-related tumors is unknown, though unlikely.

Animals↗
PubMed1984

A subchronic inhalation study on the toxicologic potential of ethylene oxide in B6C3F1 mice.

Four groups of B6C3F1 mice, each containing 30 per sex, were exposed to ethylene oxide (EtO) vapor at target concentrations of 250, 100, 50, 10, or 0 ppm which are equivalent to 450, 180, 90, 18, and 0 mg/m3, respectively. The actual mean chamber concentrations were 236, 104, 48, 10, and 0 ppm, respectively. After an exposure regimen of 6 hr per day, 5 days per week, for 10 weeks (males), or 11 weeks (females), urine and blood samples were taken for clinical pathologic evaluation and selected tissues were weighed and examined by light microscopy. Statistically significant findings that could be indicative of a toxic response were observed in the 250-ppm exposure group. These included minimal changes in certain erythroid parameters, increased liver weight, decreased testicular weight, and decreased spleen weight which was noted also in the 100-ppm group. However, there were no microscopic findings to support or explain any of these apparently treatment-related effects. Results of a neuromuscular screening test indicated that certain reflex responses and locomotor activities were altered in the EtO-exposed animals. A dose-related trend of response in the 250-, 100-, and 50-ppm exposure groups was noted in the evaluation of locomotor function; however, because of the small sample size, it was not possible to determine a threshold concentration for this effect. There were no accompanying histopathologic alterations in muscle and central or peripheral nervous tissue.

Animals↗
PubMed1984

Interactions between bromobenzene dose, glutathione concentrations, and organ toxicities in single- and multiple-treatment studies.

A single oral dose of 4.0 mmol/kg bromobenzene transiently depleted hepatic and renal reduced nonprotein sulfhydryl group (NPS) concentrations, caused hepatocellular necrosis, and increased serum glutamic-pyruvic transaminase activity in male Fischer 344 rats. The depletion of NPS had partially reversed by 24 hr, and NPS concentrations were approximately twice normal values by 48 hr post-treatment. When the effects of single and repeated (once daily for 2, 4, or 10 days) treatments with 4.0 mmol/kg were compared, it was apparent that the severity of hepatotoxicity lessened and the percentage depletions of hepatic and renal NPS concentrations decreased with increasing length of bromobenzene treatment. There were essentially no signs of toxicity following the tenth treatment with 4.0 mmol/kg. Single-treatment studies indicated the following dose-response: 2.0 mmol/kg bromobenzene depleted liver NPS and was hepatotoxic, 0.5 mmol/kg caused a lesser depletion of liver NPS and was not (overtly) hepatotoxic, and 0.0625 mmol/kg was the maximum dose that did not deplete liver NPS. The responses to single and multiple (ten) treatments with these representative doses were compared. Liver injury was observed after a single but not after the tenth daily treatment with 2.0 mmol/kg. Both the single and the tenth administrations of 2.0 mmol/kg depleted hepatic NPS, but the percentage of depletion was greater after the first than after the tenth dose. Liver injury was not detected with lower dose regimens. The patterns of NPS depletion in liver and kidney were similar after single or multiple (ten) treatments. The minimum NPS concentrations produced, however, were lower after single than after multiple treatments. The molar amounts of liver NPS depleted after the tenth treatment appeared to be equivalent to or greater than those after the first, but prior bromobenzene exposure resulted in a higher concentration of tissue NPS being present at the time of the final treatment. Thus, the minimum tissue concentrations of NPS were greater after multiple treatments than after single treatments, despite the loss of equivalent amounts of NPS. It is concluded from these studies that repeated treatment produces resistance to bromobenzene hepatotoxicity. This protective adaptation may be due to a chemically induced increase in liver glutathione concentration.

Animals↗
PubMed1983

Ethylene glycol monobutyl ether: acute, 9-day, and 90-day vapor inhalation studies in Fischer 344 rats.

The acute 4-hr LC50 (with 95% confidence limits) for Fischer 344 rats was determined to be 486 (339 to 696) ppm of ethylene glycol monobutyl ether (EGBE) for males and 450 (315 to 645) ppm for females. Notable observations included loss of coordination, red stained urine, and enlarged discolored kidneys at 867 and 523 ppm. In a subsequent study, rats were exposed for 9 days (6 hr/day) to EGBE concentrations of 245, 86, 20, or 0 (control) ppm. There were significant depressions of red blood cell (RBC) count (approximately 20% below control values), hemoglobin (Hgb), and mean corpuscular hemoglobin (MCH) concentration and increases in nucleated erythrocytes, reticulocytes, and lymphocytes in males and females of the 245 ppm group. Decreased body weight gains and increased liver weights were also found. A 14-day postexposure recovery showed substantial reversal of the affected blood parameters. Similar, but less marked, hematologic effects were observed in rats exposed to 86 ppm of EGBE, while rats of the 20 ppm group were indistinguishable from controls. In a 90-day study, rats were exposed to EGBE concentrations of 77, 25, 5, or 0 ppm for 13 weeks (6 hr/day, 5 days/week). Slight, but statistically significant, decreases in RBC (13% below control) and Hgb, accompanied by an increase in MCH (11% above control) were observed in the 77 ppm-exposed females after 6 weeks. At the conclusion of the 90-day exposure regimen, the hematologic effects seen in the females had lessened (RBC was 7% below control) or returned to control value ranges. Furthermore, no treatment-related differences were found in body weight, organ weights, urine or serum chemistries, gross lesions, or microscopic lesions in males or females. There were no significant biological effects in rats exposed subchronically to 25 or 5 ppm. The subtle hematologic findings of these studies confirm the known RBC perturbations of EGBE.

Animals↗
PubMed1983

Teratogenicity study of ethylene glycol in rats.

Ethylene glycol was administered in the diet to pregnant Fischer 344 rats on days 6 through 15 of gestation. Target dosage levels were 1.0, 0.2, 0.04, and 0.00 g/kg/day. There was no maternal toxicity, embryotoxicity, or increased incidence of malformations in fetuses from doses dams. Positive control dams received 500 mg/kg of hydroxyurea on gestation day 11 and had fetuses with numerous soft tissue and skeletal malformations. Results are interpreted as preliminary indication of lack of teratogenicity of ethylene glycol.

Abnormalities, Drug-Induced↗
PubMed1981

Spontaneous proteus nephritis among male C3H/HeJ mice.

The spontaneous occurrence of nephritis and resultant mortality was investigated among 2,836 control or treated (dermal carcinogenesis bioassays) C3H/HeJ male mice. Overall incidence of nephritis putatively caused by Proteus mirabilis was 1.2%. Incidences were similar in control and treated mice and ranged from 2.5--32.5% among 73 unrelated treatment or control groups. Diagnosis was based upon characteristic gross or histologic renal lesions. Grossly affected kidneys contained either multiple, discrete tan foci or elevated pale tan patches. Histologic renal lesions consisted of a multifocal necropurulent nephritis with numerous gram negative bacteria present in affected tubules. Necrotizing pyelitis and papillitis usually was present, an necropurulent cystitis was present in half of the cases examined histologically. Proteus mirabilis, isolated in pure culture from an affected kidney, produced similar renal lesions after intraperitoneal or intravenous inoculation of clinically normal C3H/HeJ males. The organism was reisolated from the kidneys of the experimentally produced cases. It was concluded that nephritis putatively caused by Proteus mirabilis was an important cause of mortality in male C3H/HeJ mice.

Animals↗
PubMed1979

Harderian gland dacryoadenitis in rats resulting from orbital bleeding.

Localized necrotizing inflammation of the Harderian gland was a sequela to obtaining blood samples from rats by the orbital bleeding technique. The lesion affected a few adjoining lobules that were adjacent to ocular muscles, in contrast to the widespread inflammation of the Harderian gland which results from sialodacryoadenitis virus infection. Lesions resolved in 4 weeks by atrophy of acini in affected lobules with associated mononuclear cell inflammation and fibrosis.

Animals↗
PubMed1979

Frequency of hydronephrosis in Wistar rats.

Kidneys from 1806 Wistar rats were examined grossly for hydronephrosis and ureteral dilation. Hydronephrosis was seen more often on the right side (11%) than the left (0.3%). Overall frequency of hydronephrosis in males (181/1305) was greater than in females (23/501), and the frequency was statistically greater in male rats aged 5,6,8 and 9 weeks than in age-matched females.

Animals↗
PubMed1978

Transplacental lung tumorigenesis in the athymic mouse.

Female BALB/c nu/+ mice, pregnant by nu/+ males (nu: gene for hairlessness-athymia) were given injections of urethan, a transplacental tumorigen, on Day 17 or 19 of gestation. After an average of 16 weeks under clean conventional conditions, the incidence of primary lung tumors was similar in nude and normal offspring treated with carcinogen on either gestational day, with a higher incidence after treatment of Day 19. Thus, the absence of thymus did not affect the occurrence of transplacentally induced primary lung tumors or alter the well-known perinatal increase in sensitivity. Histologically, the nu/nu tumors differed from normal in the appearance of many atypical basophilic cells and in a tendency to invade both the parenchyma and the pleural surface. These results suggested progression of the lung adenomas to a more atypical, invasive form, a progression that may have occurred prematurely in the absence of thymus-dependent immune response.

Adenoma↗