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Biomedical subjects

R D Phillips

Publications and source records attributed to R D Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1989

The dermal carcinogenic potential of unrefined and hydrotreated lubricating oils.

Unrefined lubricating oils contain relatively high levels of polycyclic aromatic hydrocarbons (PAH) and have been shown to induce tumors in mouse skin. Exxon has developed a new method of refining these materials, a severe hydrotreatment process that is optimized for PAH removal. The specific objectives of the current study were to assess PAH reduction and then to evaluate directly the dermal carcinogenic potential of the materials that spanned the range of products produced by this method. The test samples included unrefined light and heavy vacuum distillates from a naphthenic crude oil, as well as the corresponding severely hydrotreated products. Two sets of samples were prepared to assess the effects of various operating parameters in the reactor. Additionally, positive (benzo[a]pyrene), negative (white mineral oil) and vehicle (toluene) control groups were included to assess the sensitivity and specificity of the bioassay. Each sample was applied in twice-weekly aliquots to the backs of 40 male C3H mice. In the analytical studies, significant reductions in the levels of several specific PAH were demonstrated. In the dermal carcinogenesis studies, the unrefined oils and the positive control induced tumors and also significantly reduced survival. None of the mice treated with severely hydrotreated oils or with the negative or vehicle controls developed skin tumors, and survival of these mice was not significantly different from the control. Thus, the data demonstrated that this new, severe hydrotreatment process was an effective means of converting carcinogenic feedstocks to non-carcinogenic products.

Animals↗
PubMed1989

Amino acid composition protein quality and water-soluble vitamin content of germinated cowpeas (Vigna unguiculata).

Amino acid composition, protein digestibility, calculated protein efficiency ratio (C-PER and DC-PER), chemical scores and water-soluble vitamin content of cowpea seeds germinated at 25 degrees C or 30 degrees C for 24 h were determined. Also, the effect of processing steps (heated-air drying, decortication and cooking) on these parameters were examined. Germination had little effect on amino acid profile of cowpeas. In vitro protein digestibility was not improved significantly by germination nor by decortication but was improved by cooking. C-PER and DC-PER ranged from 1.95 to 2.21 and from 1.63 to 1.82, respectively. DC-PER compared well with reported rat PER of cowpea products and seemed more sensitive than C-PER. Based on whole egg values, chemical scores ranged from 37.7 to 45.8% (mean +/- SD; 42.2 +/- 2.4%). Germination increased the contents of niacin, thiamin and riboflavin significantly. Decortication resulted in up to 30% loss in niacin while thiamin content was reduced 41% by cooking.

Amino Acids↗
PubMed1988

Mutagenicity studies on ketone solvents: methyl ethyl ketone, methyl isobutyl ketone, and isophorone.

3 ketone solvents (methyl ethyl ketone (MEK), methyl isobutyl ketone (MiBK), and isophorone) were tested for potential genotoxicity. The assays of MEK and MiBK included the Salmonella/microsome (Ames) assay, L5178Y/TK+/- mouse lymphoma (ML) assay, BALB/3T3 cell transformation (CT) assay, unscheduled DNA synthesis (UDS) assay, and micronucleus (MN) assay. Only the ML, UDS, and MN assays were conducted on samples of isophorone. No genotoxicity was found for MEK or isophorone. The presence of a marginal response only at the highest, cytotoxic concentration tested in the ML assay, the lack of reproducibility in the CT assay, and clearly negative results in the Ames assay, UDS and MN assays, suggest that MiBK is unlikely to be genotoxic in mammalian systems.

Animals↗
PubMed1988

Play therapy in health care settings: promises never kept?

This article examines the variety of claims made about the effectiveness of play therapy in health care settings. The claims are organized into four categories of "promises": (a) mastery, autonomy, and control; (b) cooperation and communication; (c) coping with anxiety and fear; and (d) learning and information giving. The empirical questions within each promise are identified and relevant experimental research is discussed. The conclusion is that play therapy has not yet delivered on its promises in health care settings.

Anxiety↗
PubMed1987

Developmental studies of Hanford miniature swine exposed to 60-Hz electric fields.

Evaluations of reproductive and developmental toxicology, including teratology, were included as part of a broad screening study in Hanford Miniature swine (HMS) to detect effects of exposure to electric fields. One group (E) was exposed to a uniform, vertical, 60-Hz, 30-kV/m electric field for 20 h/day, 7 days/week; sham-exposed (SE) swine were housed in a separate, environmentally equivalent building. The first generation (F0) gilts were bred after 4 months of study; some were killed for teratologic assays at 100 days of gestation (dg), and the others produced an F1 generation of offspring. The pooled incidence of terata in these litters (teratologic assays and live births) was similar in the E and SE groups. The F0 females, which produced the F1 generation, were bred again after 18 months of exposure and were killed at 100 dg. Malformation incidence in E litters (75%) was significantly greater than in SE litters (29%). No consistent differences in litter size, fetal mass, or mass of fetal organs were detected. The F1 gilts were bred at 18 months of age; defective offspring were found in significantly more of the E litters (71%) than in SE litters (33%). These F1 females were bred again 10 months later and teratologic assays were performed on their second litters at 100 dg. The percentage of litters with malformed fetuses was essentially identical in the E and SE groups (70% and 73%, respectively). There appears to be an association between chronic exposure to a strong electric field and developmental effects in swine, although the change in incidence of malformations between generations and between the first and second breedings makes it impossible to conclude unequivocally that there is a cause-and-effect relation.

Animals↗
PubMed1987

Reproduction and development in rats chronologically exposed to 60-Hz electric fields.

Previous studies have raised the possibility of reproductive and developmental changes in miniature swine chronically exposed to a strong 60-Hz electric field. Two replicate experiments on rats were performed to determine if similar changes could be detected in animals exposed under a comparable regime, which was based on average, induced-current densities and on the chronology of reproductive development, as dosimetrically and biologically scaled. Beginning at three months of age, female rats of the F0 generation and their subsequent offspring were chronically exposed to a 60-Hz electric field (100 kV/m unperturbed) for 19 h/day for the duration of experimentation. After four weeks of exposure, F0 female rats were mated to unexposed male rats during the field-off period. No significant developmental effects were detected in their litters, confirming our previous results with swine and rats. The F0 females were mated for a second time at 7.2 months of age, and the fetuses were evaluated shortly before term. In the first experiments, the incidence of intrauterine mortality was significantly less in exposed than in sham-exposed litters, and there was a tendency (P = .12) for an increased incidence of malformed fetuses in exposed litters. Neither end point was significantly affected in the second experiment. Copulatory behavior of the female F1 offspring, which were bred at three months of age, was not affected in either experiment. There was a statistically significant decrease in the fertility of F1 exposed females and a significant increase in the fraction of exposed litters with malformed fetuses in the first experiment; both end points were essentially the same in the sham and exposed groups of the second experiment. That the significant effects detected in the first experiment were not seen in the second may be attributed to random or biological variation. Alternatively, the finding may indicate that the response threshold for induction of malformations lies near 100 kV/m.

Animals↗
PubMed1987

The genetic toxicity of 1,2-dibromo-3-chloropropane, 1,2-dibromo-3-chloro-2-methylpropane, and 1,2,3-tribromo-2-methylpropane.

1,2-Dibromo-3-chloro-2-methylpropane (DBCMP) and 1,2,3-tribromo-2-methylpropane (TBMP) are contaminants formed during the manufacture of bromobutyl rubber. These chemicals are structurally similar to 1,2-dibromo-3-chloropropane (DBCP), a known genotoxin and rodent carcinogen. The present study compared the genotoxic properties of DBCMP and TBMP to those of DBCP. In the Salmonella assay, DBCP was positive in strains TA-98, TA-100 and TA-1535 in the presence of exogenous activation; DBCP was weakly active in TA-1535 in the absence of activation. Neither DBCMP nor TBMP produced reproducible evidence of mutagenic activity in the Salmonella assay despite the use of several different variations of this test. In the mouse lymphoma gene mutation assay, DBCP and TBMP were positive in the presence and absence of activation, while DBCMP was positive only in the absence of activation. All three test compounds were active in the Syrian hamster embryo morphologic transformation assay. The results indicated that both DBCMP and TBMP exhibited some genotoxic activity as did DBCP. The presence of the methyl group on the 2-carbon position essentially eliminated the mutagenicity of DBCMP and TBMP in the Salmonella assay.

Animals↗
PubMed1987

A 14-week vapor inhalation toxicity study of methyl isobutyl ketone.

In a 2-week probe study male and female Fischer-344 rats and B6C3F1 mice were exposed 6 hr/day to 2000, 500, 100, or 0 ppm methyl isobutyl ketone (MIBK). At 2000 ppm there was a slight increase in male rat liver weight (absolute and relative). The only changes observed histologically were increases in regenerative tubular epithelia and hyalin droplets in kidneys of male rats exposed to 2000 or 500 ppm. Exposure levels for a subchronic study were 0, 50, 250, or 1000 ppm methyl isobutyl ketone vapors 6 hr/day, 5 days per week, for 14 weeks. The 14 weeks of exposure had no adverse effect on the clinical health or growth of rats or mice. Male rats and male mice exposed to 1000 ppm MIBK had a slight but statistically significant increase in liver weight and the liver weight/body weight ratio. Liver weight was also increased slightly in male mice exposed to 250 ppm. No gross or microscopic hepatic lesions related to MIBK exposure were observed. Furthermore, the only microscopic change observed was an increase in the incidence and extent of hyalin droplets within proximal tubular cells of the kidneys of male rats exposed to 250 and 1000 ppm of MIBK. The relevance of the male rat kidney tubular effect to humans is not known. In conclusion, other than the male rat kidney effect, exposure of male and female rats and mice to MIBK at levels up to 1000 ppm for 14 weeks was without significant toxicological effect.

Administration, Inhalation↗
PubMed1987

Developmental toxicity evaluation of inhaled methyl isobutyl ketone in Fischer 344 rats and CD-1 mice.

Pregnant Fischer 344 rats and CD-1 mice were exposed to methyl isobutyl ketone vapor (CAS No. 108-10-1) by inhalation on Gestational Days 6 through 15 at concentrations of 0, 300, 1000, or 3000 ppm (mean analytical values of 0, 305, 1012, and 2997 ppm, respectively). The animals were sacrificed on Gestational Day 21 (rats) or 18 (mice), and live fetuses were examined for external, visceral, and skeletal alterations. In rats, exposure to 3000 ppm resulted in maternal toxicity expressed as clinical signs, decreased body weight and body weight gain, increased relative kidney weight, and decreased food consumption, and in fetotoxicity expressed as reduced fetal body weight per litter and reductions in skeletal ossification. In mice, exposure to 3000 ppm resulted in maternal toxicity expressed as exposure-related increases in deaths (12.0%, 3/25 dams), clinical signs, and increased absolute and relative liver weight, and in fetotoxicity expressed as increased incidence of dead fetuses, reduced fetal body weight per litter, and reductions in skeletal ossification. No treatment-related increases in embryotoxicity or fetal malformations were seen in either species at any exposure concentration tested. There was no evidence of treatment-related maternal, embryo, or fetal toxicity (including malformations) at 1000 or 300 ppm in either species.

Administration, Inhalation↗
PubMed1985

Monochlorodiisobutylene vapor: acute and 9-day inhalation studies in Fischer-344 rats and B6C3F1 mice.

Acute and 9-day repeated exposures to monochlorodiisobutylene (CDIB) were conducted in male and female Fischer-344 rats and B6C3F1 mice. The 4-hr LC50 values for these animals ranged between 1400 and 2100 ppm. Animals in the 9-day study were exposed at a mean concentration of 478, 97, or 25 ppm of CDIB for 6 hr per day. Treatment-related effects differed between species in this study. Body weight change was decreased in rats. Morphologic changes in the kidneys with accompanying polyuria and hematuria/hemoglobinuria were observed in male rats. The only effect observed at 25 ppm was a low incidence of hematuria/hemoglobinuria in male rats. Mice appeared unaffected by exposure to CDIB at levels as high as 478 ppm.

Animals↗
PubMed1984

Studies on prenatal and postnatal development in rats exposed to 60-Hz electric fields.

A series of three experiments was performed to determine the effects of 30-day exposures to uniform 60-Hz electric fields (100 kV/m) on reproduction and on growth and development in the fetuses and offspring of rats. In the first experiment, exposure of females for 6 days prior to and during the mating period did not affect their reproductive performance, and continued exposure through 20 days of gestation (dg) did not affect the viability, size, or morphology of their fetuses. In the second experiment, exposure of the pregnant rat was begun on 0 dg and continued until the resulting offspring reached 8 days of age. In the third experiment, exposure began at 17 dg and continued through 25 days of postnatal life. In the second and third experiments, no statistically significant differences suggesting impairment of the growth or survival of exposed offspring were detected. In the second experiment, a significantly greater percentage of the exposed offspring showed movement, standing, and grooming at 14 days of age than among-sham-exposed offspring. There was a significant decrease at 14 days in the percentage of exposed offspring displaying the righting reflex in the second experiment and negative geotropism in the third experiment. These differences were all transient and were not found when the animals were tested again at 21 days of age. Evaluation of the reproductive integrity of the offspring of the second experiment did not disclose any deficits.

Age Factors↗
PubMed1984

Attempts to produce taste-aversion learning in rats exposed to 60-Hz electric fields.

A measure of taste-aversion (TA) learning was used in three experiments to 1) determine whether exposure to intense 60-Hz electric fields can produce TA learning in male Sprague-Dawley rats, and 2) establish a dose-response function for the behavior in question. In Experiment 1, four groups of eight rats each were distributed into one of two exposures (69 +/- 5 kV/m or 133 +/- 10 kV/m) or into one of two sham-exposure groups. Conditioning trials paired 0.1% sodium saccharin in water with 3 h of exposure to a 60-Hz electric field. Following five conditioning trials, a 20-min, two-bottle preference test between water and saccharin-flavored water failed to reveal TA conditioning in exposed groups. In Experiment 2, four groups of eight rats each (34 +/- 2 kV/m or 133 +/- 10 kV/m and two sham-exposed groups) were treated as before. Electric-field exposure had no effect on TA learning. Experiment 3 tested for a possible synergy between a minimal dose (for TA learning) of cyclophosphamide (6 mg/kg) and 5 h of exposure to 133 +/- 10 kV/m electric fields in a dark environment under conditions otherwise similar to those of Experiments 1 and 2. The results indicated no TA learning as reflected in the relative consumption of saccharin.

Animals↗
PubMed1984

Effect of C10-C11 isoparaffinic solvent on kidney function in Fischer 344 rats during eight weeks of inhalation.

Two groups of 50 male and 50 female Fischer 344 rats were exposed by inhalation to either 5.48 g/m3 (900 ppm) or 1.83 g/m3 (300 ppm) of C10-C11 isoparaffin (IP) 6 hr/day, 5 days/week for 8 weeks to evaluate renal function and histologic effects. Another group of rats (50/sex) was air exposed and served as controls. Urine and blood were collected from 10 male and 10 female rats of each group after 1, 4, and 8 weeks, and following a 4-week period of recovery. The ability of males to concentrate urine was reduced at 4 and 8 weeks of exposure to either level of IP. Following the 4-week recovery period, the urine concentrating ability of the exposed groups showed evidence of recovery. Following 4 and 8 weeks of exposure, glucose, protein, and epithelial cell excretion in urine of males was higher in the exposed groups than in that of controls. Creatinine clearance decreased after 8 weeks in the male high exposure group. After 4 weeks of recovery, urine glucose, protein, epithelial cell exfoliation, and creatinine clearance returned to control levels in exposed male rats. Overall, the effect on kidney function in male rats was mild, with evidence of near complete recovery. Histologic changes in exposed male rats compared to controls included an increased incidence of regenerative tubular epithelia and tubules dilated at the corticomedullary junction with proteinaceous debris in the tubules. No functional or histologic changes were observed in exposed female rats.

Animals↗
PubMed1984

Subchronic inhalation exposure of dearomatized white spirit and C10-C11 isoparaffinic hydrocarbon in Sprague-Dawley rats.

Groups of 35 male and 35 female Sprague-Dawley rats were exposed to either Dearomatized White Spirit (DAWS) vapor at concentrations of 1.97 and 5.61 g/m3 or C10-C11 Isoparaffinic Hydrocarbon (IPH) vapor at concentrations of 1.91 and 5.62 g/m3. These concentrations were targeted for the recommended occupational exposure limits and three times that value, respectively. Exposures were 6 hr-day, 5 days/week for 12 weeks. Following Weeks 4, 8, and 12 of exposure, a total of 10, 10, and 15 rats, respectively, from each group were sacrificed. Clinical chemistry and hematology parameters were measured in blood samples taken immediately prior to sacrifice, and selected organs were removed and weighted. Twenty-three organs and tissues from each animal were examined microscopically. There were no deaths during the course of this study related to either DAWS or IPH. Mean body weights were significantly lower than controls in male rats following exposure to 5.61 g/m3 DAWS, and 5.62 or 1.91 g/m3 IPH. Body weights were not affected in females. The primary effects from DAWS or IPH exposure were observed in the kidneys of male rats only from both exposure groups beginning at Week 4. Evidence of mild tubular toxicity, such as regenerative tubular epithelia and dilated tubules containing proteinaceous casts, was observed at the corticomedullary junction. The incidence and severity appeared to increase with increasing concentration and exposure duration. There were scattered instances of statistically significant increases in liver and kidney weights in both males and females. With the exception of the mild male rat tubular nephrotoxicity, other significant toxic effects were not observed at levels tested.

Alkanes↗
PubMed1984

Kidney structural changes in rats following inhalation exposure to C10-C11 isoparaffinic solvent.

Kidney tissues from Fischer 344 rats exposed by inhalation to either 5.48, 1.83, or 0.0 g/m3 of C10-C11 isoparaffinic solvent vapor for 5, 20 and 40 days (6 h/day, 5 days/week), followed by a 4-week recovery period, were examined by light microscopy (LM) and electron microscopy (EM). At the LM level, an increased incidence of protein droplets was found in the cytoplasm of renal tubular epithelial cells of the exposed male rats relative to controls. Other renal changes observed by LM in the exposed male rats included foci of regenerative epithelium and tubular dilatation with intratubular protein occurring between the inner and outer stripe of the medulla. By EM, the protein droplets were electron dense, angular, crystalline-like structures which were surrounded by acid phosphatase positive reaction product corresponding to remnants of membrane-bound phagolysosomes. After 20 and 40 days of exposure there was focal loss of the brush border, with degeneration and sloughing of necrotic cells. Following a 4-week recovery period reversal of the exposure-related tubular changes was indicated by EM. The kidney changes observed in male rats following exposure to light hydrocarbons have not been observed in female rats or other species and may be unique to the male rat.

Acid Phosphatase↗
PubMed1983

The influence of electric field exposure on bone growth and fracture repair in rats.

Rats were exposed to a 60-Hz electric field at an unperturbed field strength of 100 kV/m to determine its affect on bone growth and fracture repair. Exposure of immature male and female rats for 20 h/day for 30 days did not alter growth rate, cortical bone area, or medullary cavity area of the tibia. In another experiment, midfibular osteotomies were performed and the juvenile rats were exposed at 100 kV/m for 14 days. Evaluation by resistance to deformation and breaking strength indicated that fracture repair was not as advanced in the exposed animals as in the sham-exposed animals. In another experiment measurements of resistance to deformation were made in adult rats at 16, 20, and 26 days after osteotomy. Fracture repair was slower in exposed compared to control animals at day 20 and, to a lesser extent, at day 16, but not at day 26.

Animals↗
PubMed1983

Hematologic and serum chemistry studies in rats exposed to 60-Hz electric fields.

Numerous hematologic and serum chemistry variables were examined in rats exposed to unperturbed 60-Hz electric fields at 100 kV/m for 15, 30, 60, or 120 days. Each study was replicated once. Rigorous statistical evaluations of these data did not detect any consistent effect of the electric field for exposures of up to 120 days. It was, however, not unusual in any individual study to detect certain variables that were significantly different between the exposed and sham-exposed animals. This emphasizes the need for replicate designs and appropriate statistical analyses when investigating chemical or physical insults that may have minimal influence on biologic function.

Animals↗