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Biomedical subjects

B Ballantyne

Publications and source records attributed to B Ballantyne.

At least 55 records · Page 3Linked to original sources

Acute, 9-day, and 13-week vapor inhalation studies on ethylene glycol monohexyl ether.

At ambient conditions, the low vapor pressure of ethylene glycol monohexyl ether (EGHE) allows for a maximum vapor concentration of approximately 85 ppm. In an acute inhalation study on Wistar albino rats, a 4-hr exposure to 83 ppm EGHE produced no clinical signs, body weight effects, mortality, or macroscopic lesions in thoracic or abdominal organs. Fischer 344 rats exposed for 9 days (6 hr/day) over an 11-day period, to 0 (control), 19, 41, or 84 ppm EGHE had decreased body weight gains and increased liver to body weight values at 84 ppm EGHE. No alterations of the hematology parameters or the morphology of the testes or liver were observed. In a subsequent study, rats were exposed to mean EGHE concentrations of 0 (control), 20, 41, or 71 ppm for 6 hr/day, 5 days/week, for 13 weeks. Urogenital wetness was observed in all EGHE-exposed groups of females and in males of the 71-ppm group. Decreased body weight gains were observed in both sexes of the 71-ppm group, and a slight decrease was also observed in females of the 41-ppm group. Increased absolute and/or relative liver weights were observed in both sexes of the 71-ppm group and to a lesser extent in the 41-ppm group. Possibly related to these findings in the liver were decreases in serum transaminases (aspartate and alanine aminotransferase) and sorbitol dehydrogenase, with an increase in alkaline phosphatase observed in the 71-ppm group of female rats. However, there were no gross or histopathologic lesions found to indicate impairment of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

The comparative acute toxicity and primary irritancy of the monohexyl ethers of ethylene and diethylene glycol.

Ethylene glycol monohexyl ether (EGHE) and diethylene glycol monohexyl ether (DGHE) are glycol ethers used as industrial solvents and coating materials, and whose acute handling hazards were investigated. Acute peroral LD50 values in the rat were for EGHE 1.67 ml/kg (males) and 0.83 ml/kg (females), and for DGHE 4.92 ml/kg (males) and 3.73 ml/kg (females). Acute percutaneous LD50 values in the rabbit were for EGHE 0.81 ml/kg (males) and 0.93 ml/kg (females), and for DGHE 2.14 ml/kg (males) and 2.37 ml/kg (females). There were neither deaths nor signs of toxicity or irritancy during or following a 6-hr exposure of rats to a statically generated substantially saturated vapor atmosphere from either EGHE or DGHE at ambient temperature. Occluded dermal application with 0.5 ml test material for 4-hr in rabbits produced moderate inflammation of several days duration, and half of the animals developed necrosis; with DGHE there was minor erythema and edema of about 24-hr duration. In the more demanding conditions of the acute percutaneous toxicity study (24-hr occlusions with up to 4.0 ml/kg) both EGHE and DGHE produced persistent erythema, edema, necrosis, and ecchymoses. Rabbit eye irritation studies showed severe effects (conjunctivitis and corneal injury) with both EGHE and DGHE. The major acute handling hazards with both EGHE and DGHE are by swallowing, sustained skin contact, and splash contamination of the eye.

Administration, Cutaneous↗

Influence of housing conditions for mice on the results of a dermal oncogenicity bioassay.

Male C3H/HeJ mice were thrice weekly given 25 microliter applications of 0.25, 0.05, or 0.01% (w/w) benzo(a)pyrene (BaP) in acetone, or acetone alone, to clipped dorsal skin from 12 to 14 weeks of age for the remainder of their life spans. There were two groups of 40 mice for each treatment regimen, one group being housed in conventional stainless-steel wire mesh cages and the other in polycarbonate cages with wood shavings held in an enclosed ventilated cabinet. Under both housing conditions, tumor incidence was directly related and latency inversely related to BaP concentration. The time-adjusted incidence of epidermal neoplasms was significantly greater for the groups housed in polycarbonate cages. Mortality rates were directly related to BaP concentration and were significantly enhanced by the polycarbonate-cage housing conditions for the high and intermediate concentrations. Survival patterns for the two acetone control groups were similar. These findings indicate that differences in housing conditions can influence both the incidence and the latency of local neoplasms produced in response to the chronic application of a carcinogen in dermal oncogenesis bioassays.

Animals↗

2,4-Pentanedione: 9-day and 14-week vapor inhalation studies in Fischer-344 rats.

Fischer-344 rats, in groups of 10 males and 10 females, were exposed for 9 days (6 hr/day) to 2,4-pentanedione (2,4-PD) vapor at mean concentrations of 805, 418, 197, and 0 (control) ppm. No deaths occurred, and the only adverse signs were of sensory irritation (partial closure of eyelids, periocular and perioral wetness) at 805 ppm. Also at 805 ppm were decreased body and organ weights, lymphocytosis, and moderate inflammation of the nasal mucosa. At 418 ppm there was a decrease in body weight gain and mild inflammation of the nasal mucosa. Apart from minimal nasal mucosal inflammation, there were no effects at 197 ppm. In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-PD vapor, using groups containing 20 males and 20 females, with half being sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period. An additional 10 males were added to the 650 and 0 ppm groups for glutaraldehyde perfusion and subsequent electron microscopic examination of sciatic nerves. At 650 ppm, all females and 10 of 30 males died between the second and sixth weeks of exposure. These animals had acute degenerative changes in the deep cerebellar nuclei, vestibular nuclei and corpora striata, and acute lymphoid degeneration in the thymus. Seven of 15 male survivors of the 650 ppm group (combined 14-week and recovery sacrifices) had gliosis and malacia in the same brain regions, minimal squamous metaplasia in the nasal mucosa, decreased body and organ weights, lymphocytosis, and minor alterations in serum and urine chemistries. No ultrastructural evidence of peripheral neuropathy was observed. Except for central neuropathy, many of the adverse effects at 650 ppm were less marked in the 4-week recovery animals. No deaths occurred at 307 ppm, but females had slightly decreased body weight gains, and in both sexes there were minor alterations in hematology, serum chemistry, and urinalysis parameters, which were not present in the 4-week recovery animals. Rats exposed to 101 ppm showed no differences from the control rats. Subchronic exposure to 650 ppm of 2,4-PD vapor causes serious adverse biological effects. Under these study conditions, the minimum-effects concentration was 307 ppm, and the no-adverse effects concentration was 101 ppm.

Administration, Inhalation↗

Studies on the acute toxicity primary irritancy and genotoxic potential of 1,3,5-triacryloylhexahydro-s-triazine (TAHT).

TAHT (1,3,5-triacryloylhexahydro-s-triazine), a reactive chemical coupling agent, was highly toxic following a single peroral dose of an aqueous suspension (10% w/v) to Wistar rats, or following application of TAHT in dichloromethane (DCM) solution (10% w/v) to covered skin of New Zealand rabbits. It was moderately toxic when applied dermally as an aqueous paste. Ocular contact with 25 mg of TAHT in a 5% aqueous suspension, or of 0.5 mg of TAHT in a 10% (w/v) solution in DCM, produced severe corneal damage, iritis and blepharo-conjunctivitis. A 30-min exposure of uncovered rabbit skin to 1 mg of TAHT in a 10% (w/v) aqueous suspension produced only slight skin irritation. However, 24-h exposures to TAHT on covered skin produced erythema, edema, ecchymoses, scabs, and death depending upon dosage and vehicle. In vitro genotoxicity studies revealed no positive effects upon gene mutations (HGPRT locus) or on sister chromatid exchanges (SCEs) of CHO cells exposed to TAHT with and without a rat-liver S9 metabolic activation system. TAHT did not increase the levels of [3H]thymidine incorporation in a test for unscheduled DNA synthesis with primary rat hepatocytes. In contrast, substantial increases in the number of chromosome breaks and rearrangements were observed in chromosome preparations used for the SCE analyses. The clastogenic activity of TAHT was confirmed in an in vitro chromosome aberration test with CHO cells. Treatment-related increases in chromosome breakage were observed at two independent sampling times and positive effects did not depend upon the presence or absence of a metabolic activation system. Clastogenic activity of TAHT was also demonstrated in vivo in a micronucleus test using mouse peripheral polychromatic erythrocytes. Significant, treatment-related increases in micronucleated polychromatic erythrocytes were obtained at two of three sampling times. The high degree of mammalian toxicity, severe eye irritancy and the in vitro and in vivo clastogenicity indicate that TAHT should be handled as a hazardous material using suitable caution and protective equipment.

Animals↗

The acute toxicity and primary irritancy of 2,4-pentanedione.

2,4-Pentanedione was found to have acute peroral LD50 values (with 95% confidence limits) in the rat of 0.78 (0.66-0.91) ml/kg for males and 0.59 (0.51-0.70) ml/kg for females, and acute percutaneous LD50 values by 24 hr occluded contact on the rabbit of 1.41 (0.80-2.49) ml/kg for males and 0.81 (0.59-1.12) for females. Lt50 values for exposure of rats to saturated vapor atmospheres were 52 min (7060 ppm) for males and 55 min (7912 ppm) for females. The 4 hr LC50 value for rats was 1224 (1063-1409) ppm for combined male and female data. A 4 hr occluded contact with 0.5 ml produced mild local erythema and edema. Instillation of 0.1 ml into the inferior conjunctival sac, produced mild conjunctivitis of less than 24 hr duration without corneal injury.

Administration, Inhalation↗

Subchronic inhalation toxicology of carbon fibers.

Male Sprague Dawley rats were exposed to carbon fibers 7 microns in diameter and 20 to 60 microns in length, for six hours a day and five days a week for up to 16 weeks at an average chamber concentration of 20 mg/m3. Rats were killed at 4, 8, 12, and 16 weeks of exposure and after a 32-week postexposure recovery period. A similar number of control rats exposed only to air were killed at the same times. Pulmonary function tests, conducted just prior to the animals' death, did not demonstrate any significant or consistent changes. The only pulmonary finding that could be causally related to the subchronic inhalation of carbon fibers was phagocytosis of the inhaled particles by alveolar macrophages. This physiologic response was not accompanied by any local reactive pulmonary inflammation or fibrosis.

Animals↗

Intramuscular prednisolone pretreatment does not influence the dermal lesions induced by topical sulfur mustard.

The effect of a single intramuscular injection of prednisolone sodium phosphate (14.3 mg/kg) on the development and severity of dermal lesions induced by topical sulfur mustard was investigated in guinea pigs. Control animals received sulfur mustard alone, topical sulfur mustard and intramuscular saline, intramuscular prednisolone alone, or intramuscular saline alone. With topical sulfur mustard alone there were typical mustard lesions consisting of epidermal necrosis and hyalinization, with acute inflammation and necrosis in the dermis, the severity and extent of which were dose-related. Systemic prednisolone therapy had no influence on the nature, severity or progression of the dermal histopathologic response to topical sulfur mustard.

Animals↗

The sensitizing potential of primary amyl acetate in the guinea pig.

Primary amyl acetate is a liquid mixture of the isomeric forms of pentyl acetate, which is used as a volatile organic solvent. Because of the possibility for skin contact, primary amyl acetate was investigated for its potential to cause allergic contact dermatitis. Using a guinea pig maximization procedure, primary amyl acetate was found to be a possible marginal skin sensitizer.

Animals↗

Acute toxicity and primary irritancy of 2-amino-3,5-dicyano-4-o-chlorophenyl-6-ethoxypyridine.

2-Amino-3,5-dicyano-4-o-chlorophenyl-6-ethoxypyridine (ACCPE) is a water soluble compound formed during the alkaline treatment of the alcoholic liquor in the production of 2-chlorobenzylidene malononitrile (CS). The acute toxicity and primary irritancy of ACCPE and CS were investigated and compared. Both perorally and intravenously, ACCPE was significantly less acutely toxic than CS. Also, whilst CS was a moderate dermal and eye irritant, ACCPE was not a primary skin irritant and only marginally irritating to the eye. ACCPE presents a significantly lower acute handling hazard than does CS.

Administration, Oral↗

The acute toxicity and primary irritancy of N-benzyl-N,N-dimethylamine.

N-Benzyl-N,N-dimethylamine (BDMA), a polyester foam catalyst, was determined to have LD50 values of 0.65 (0.48-0.88) ml/kg perorally in the rat, and 1.66 (1.35-2.04) ml/kg by 24-hr occluded dermal contact in rabbits. The Lt50 for saturated vapor atmosphere exposure of rats was 35.4 min, and the 4-hr LC50 was 373 (311-447) ppm for rats and mice. Histological examination of the respiratory tract of animals exposed to BDMA concentrations of 277 ppm or higher revealed acute inflammatory changes in the nasal mucosa and pulmonary congestion. Unoccluded skin contact with 0.01 ml undiluted BDMA in rabbits produced moderate local erythema and edema. A 4-hr occluded contact resulted in local necrosis. Severe eye irritancy was produced by 0.005 ml undiluted BDMA and 0.5 ml 5% BDMA in propylene glycol; 1% BDMA was nonirritant to the eye. BDMA should be regarded as an acutely hazardous material by all routes of exposure.

Administration, Oral↗

The acute toxicity and primary irritancy of 2-ethyl-1,3-hexanediol.

2-Ethyl-1,3-hexanediol (EHD), an insect repellant, was found to have acute peroral LD50 values in the rat of 9.85 ml/kg (males) and 4.92 ml/kg (females). Acute percutaneous LD50 values in the rabbit were 10.8 ml/kg (males) and 9.51 ml/kg (females). There were neither deaths nor signs of toxicity during or following a 6 hr exposure to a statically or dynamically generated substantially saturated vapor atmosphere. A 4 hr exposure to a high concentration (3.8 mg/liter) of a respirable aerosol of EHD (mass median aerodynamic diameter of 2.0 um) produced only minor signs of irritation during exposure, but no signs of toxicity. Occluded dermal contact with EHD on rabbits (4 and 24 hr) produced mild local erythema and, in several animals, edema. Contamination of the eye with EHD (0.005 to 0.1 ml) produced marked to severe conjunctivitis, with moderate iritis and diffuse corneal injury; healing occurred in most animals within 3 to 7 days. The major acute hazards with EHD are by swallowing and, to a greater extent, by contamination of the eye.

Administration, Oral↗

The influence of pralidoxime mesylate on the measurement of cyanide concentrations in solutions.

Pralidoxime mesylate (P2S) can interfere with the colorimetric analysis for cyanide in solutions. Apparent increases in cyanide concentrations, related to the presence of P2S, are most marked at extreme pH values. At acid pH there is a direct interference by P2S, and at alkaline pH the P2S molecule is cyanogenic. Prompt analysis and the use of a cyanide separation technique minimizes the artifactual increase in measured cyanide concentrations. This effect is insignificant at pH 7.4.

Colorimetry↗

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↗

Aqueous humour pralidoxime mesylate (P2S) concentrations and intraocular tension following intramuscular P2S.

Small transient increases in rabbit intraocular tension were measured following intramuscular pralidoxime mesylate (P2S) at doses of 10, 40 or 100 mg/kg. Peak increases in tension showed some dose dependency, and although not statistically correlated with plasma or aqueous humour P2S concentrations the changes in tension followed the general time-concentration profile for P2S in these fluids. P2S was not detected in aqueous humour following 10 mg/kg, but at 40 and 100 mg/kg dose dependent concentrations were detected in aqueous humour. From experiments involving multiple injections of P2S there was no evidence for a cumulative effect of P2S on the eye. The results indicate that P2S can enter aqueous humour following its parenteral administration and is associated with changes in intraocular fluid dynamics. Whilst they also suggest that some ophthalmic side-effects of oxime therapy may be a consequence of a direct action of the oxime on the eye, they do not exclude contributions from actions at other sites.

Animals↗

Comparison of kinetic and end-point microdensitometry for the direct quantitative histochemical assessment of cytochrome oxidase activity.

Cytochrome oxidase activity has been assessed by a method of kinetic microdensitometry which involves applying tissue sections to gel films containing phenylamine substrates and measuring the rate of azine dye production by continuously recording the rate of change in extinction. Optimum conditions for the technique were defined, and the results compared with those obtained by conventional end-point microdensitometry in which sections are incubated in histochemical substrate solutions and azine dye production estimated by a single measurement of extinction at the end of the incubation period. When compared with biochemically-determined enzyme activity, kinetic microdensitometry gave a better index of the proportionate activity of cytochrome oxidase in various normal tissues than did end-point microdensitometry. In addition, the degree of inhibition of cytochrome oxidase activity in tissues removed from cyanide-poisoned animals was assessed more reliably by kinetic microdensitometry than by end-point measurements. With end-point microdensitometry, the reaction is non-linear over the comparatively long incubation times required and there is also a spontaneous reactivation of cyanide-inhibited cytochrome oxidase during incubation and thus a progressively increased rate of substrate utilization. In contrast, with kinetic microdensitometry the initial linear reaction rate is measured before significant reactivation occurs. Kinetic microdensitometry can be used for direct dynamic quantitation of enzyme activity in tissues or cells; it may be a valuable technique for quantitative histochemical confirmation or extension of biochemical studies; and it appears to be a reliable direct quantitative histochemical method for investigating in vivo inhibition of enzyme activity, where spontaneous reactivation of the enzyme-inhibitor complex may occur.

Animals↗