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Biomedical subjects

R C Myers

Publications and source records attributed to R C Myers.

At least 37 records · Page 2Linked to original sources

The acute toxicity of tris(dimethylamino)silane.

The acute handling hazards of tris(dimethylamino)silane [TDMAS] were investigated. The acute male rat peroral LD50 (with 95% confidence limits) was 0.71 (0.51-0.97) ml/kg, and the acute male rabbit percutaneous LD50 was 0.57 (0.35-0.92) ml/kg. The liquid was severely irritating to the rabbit eye and skin, and the vapor severely irritating to the rat eye. The dynamically generated saturated vapor Lt50 in female rats was 12 (9.7-15) min. The effect of varying the atmospheric concentration of vapor from TDMAS on acute inhalation toxicity was investigated by passing ordinary moist air countercurrent to liquid TDMAS metered into a slightly heated glass tube. Based on nominal concentrations, the 4 hr-LC50 for vapor from TDMAS was 734 (603-893) ppm in female rats by this procedure. Stoichiometrically, this accords with toxicity due to liberation of dimethylamine (DMA) from TDMAS. In a subsequent study designed to assess the influence of relative humidity on vapor toxicity, nitrogen was passed over heated liquid TDMAS and the resultant atmosphere was introduced into the air intake duct of the inhalation exposure chamber. Gas chromatographically measured TDMAS concentrations (+/- SD) were 395 +/- 111, 127 +/- 25, 62 +/- 8 and 23 +/- 21 ppm; the corresponding DMA vapor concentrations were 112 +/- 171, 31 +/- 43, 10 +/- 6 and 26 +/- 44 ppm. The 4-hr LC50 (males and females) was 38 (34-43) ppm TDMAS vapor. Thus, TDMAS is of moderate acute peroral and percutaneous toxicity, a severe primary skin and eye irritant, an aspiration hazard, and of high intrinsic acute inhalation toxicity, but in moist air conditions lethal toxicity may be reduced and in such circumstances DMA may be a significant factor in toxicity.

Administration, Inhalation↗

The acute toxicity and mutagenic potential of 3-methyl-2-benzothiazolinone hydrazone.

3-Methyl-2-benzothiazolinone hydrazone (MBTH), widely used in analytical laboratories, was investigated for potential handling hazards. Tested as the hydrochloride, it was found to be of moderately high acute peroral toxicity with LD50 values in rabbits of 177 mg/kg (males) and 268 mg/kg (females), and in the rat 308 mg/kg (males) and 149 mg/kg (females). The major signs of toxicity, seen at peroral doses of 125 mg/kg and above, were convulsions. Although of low acute lethal percutaneous toxicity in rats (LD50 greater than 16 g/kg), rabbits were more sensitive with one of five males dying at an applied dose of 16 g/kg, and females having an LD50 of 12.3 g/kg; convulsions were seen in rabbits having applied cutaneous doses of 4 g/kg and above. There was no evidence for cutaneous inflammation after a 4 hour occluded contact with MBTH in rabbits, although following 24 hour occlusive contact in the acute percutaneous toxicity study there was erythema, edema, desquamation and, in a few animals, local necrosis. Ocular studies in rabbits indicated that, depending on the degree of contamination, MBTH produced mild to moderate eye irritation. In keeping with its low vapor pressure, there were no adverse effects from a 6 hour exposure of rats to an atmosphere saturated with any vapor produced from solid MBTH at ambient temperature. MBTH was positive in an Ames bacterial mutagenicity assay, particularly in the absence of metabolic activation. These studies indicate MBTH to be of moderately high acute peroral toxicity, of moderate percutaneous toxicity, a mild primary skin irritant, a mild to moderate eye irritant, and produced mutations in Salmonella. There is a need for skin and eye protection, and avoidance of swallowing, when handling MBTH.

Animals↗

Acute toxicity and primary irritation of para-tertiary butylphenol.

Para-tertiary butylphenol [(PTBP); the Union Carbide Corporation trademark for this chemical is UCAR Butylphenol 4-T Flake] has applications as a raw material in the manufacture of resins and also as an industrial intermediate. Acute peroral LD50 values (95% confidence limits) of 5.4 (3.6-7.9) g/kg and 3.6 (3.0-4.4) g/kg were obtained for male and female albino rats, respectively. Occluded cutaneous applications of moistened PTBP at 16 g/kg for 24 hr produced no mortalities in male or female rabbits, but signs of local toxicity and irritation were apparent at the site of application. A 6 hr exposure to a substantially saturated vapor under static conditions produced no mortality, while a 4 hr exposure to a dynamically generated respirable dust aerosol at a concentration of 5.6 mg/L produced 20% mortality. Occluded dermal contact (4 hr) with 0.5 g moistened PTBP produced a range of effects from no reaction to necrosis. PTBP placed in the conjunctival sac of rabbits produced severe ocular injury which generally persisted for 21 days after exposure. The major hazard associated with acute exposure to PTBP appears to be the irritation produced by dermal or ocular contact.

Administration, Cutaneous↗

The acute toxicity and primary irritancy of 1-propoxy-2-propanol.

1-Propoxy-2-propanol, a widely used industrial chemical, was found to have acute peroral LD50 values in the rat of 4.92 ml/kg (males) and 2.83 ml/kg (females), with the signs of systemic toxicity being principally related to narcosis. Acute percutaneous LD50 values in the rabbit (24-hr occluded) were 4.29 ml/kg (males) and 4.92 ml/kg (females); signs of systemic toxicity were related to narcosis, and local effects were severe inflammation and corrosion. There were signs of sensory irritation of the eye during a 6-hr exposure to a dynamically generated saturated vapor atmosphere, but no signs of toxicity during exposure or in a 14-hr day postexposure observation period. A 4-hr occluded cutaneous application with 0.5 ml PP in rabbits produced mild to moderate erythema and edema of about 3 days duration, but no signs of corrosion. Contamination of the eye (0.005 to 0.1 ml PP) produced moderate to severe conjunctivitis (hyperaemia and chemosis), with mild iritis and diffuse mild keratitis; spontaneously healing occurred within 3 days (0.005 ml) to 7 days (0.1 ml). The major acute hazards with PP are by swallowing, splash contamination of the eye, and sustained skin contact.

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↗

Selenium-induced enhancement of hematoporphyrin derivative phototoxicity in murine bladder tumor cells.

The phototoxicity of hematoporphyrin derivative (Hpd) to murine bladder tumor (MBT-2) cells was studied in vitro. It was observed that selenium in the form of sodium selenite enhanced Hpd-sensitized photodamage in MBT-2 cells under conditions where selenite alone was non-toxic. Sodium selenite enhanced the fluorescence emission of Hpd and augmented the Hpd-sensitized photooxidation of tryptophan. The data suggest that sodium selenite is able to disaggregate Hpd, thereby enhancing Hpd-sensitized phototoxicity.

Animals↗

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↗

The effect of lactation on the mineral distribution profile of the rat femur by single photon absorptiometry.

The distribution of bone mineral in excised femurs from lactating and nonlactating control rats was localized and quantitated using single photon absorptiometry. Bone mineral content was measured proximodistally in nine sequential 0.32 cm increments along the femur length and then plotted as a function of the distance from the proximal end of the femur. The plots described a mineral distribution profile and revealed that bone loss following lactation was site specific, being greater in the metaphyseal regions (23-36%) than in the diaphyseal area (14-20%). The change in total bone mineral of femur caused by lactation was estimated by integrating the mineral distribution profile plots. The 28% lower bone mineral determined by this method was in close agreement with the 27% difference determined from femur dry weight measurements. Reproducibility of measurements with 10 repositionings of a single femur was within 4% at all but the 2 most distal sites. Variation in the estimated total bone mineral was 1.3%.

Animals↗

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↗

Capsular and somatic types of Pasteurella multocida from rabbits.

Capsular and somatic serotyping was performed on 79 cultures of Pasteurella multocida from rabbits. Of these isolates, 74 were capsular type A as determined by the staphylococcal hyaluronidase decapsulation test and five were type D by the acriflavine flocculation test. Somatic type 12 was the dominant serotype, and the remainder (type 1, 3, 4 and 11) were less frequent as determined by the gel diffusion precipitin test. This report is in general agreement with other recent reports with rabbit isolates and collectively they provide important serotype and epizootiological information that will be useful in the control and prevention of rabbit pasteurellosis.

Animals↗

Bone mineral analysis of the rat femur by direct photon absorptiometry.

This report describes a method using direct photon absorptiometry (DPA) for determination in vivo of the bone mineral content to bone width ratio (BMC/W) in the rat femur. A significant correlation was noted between measurements by DPA and whole femur dry weight and ash weight. Measurements were reproducible within repeated determinations of both the same and successive days. Soft tissue, rotation of the femur, or slight differences in the longitudinal positioning of the femur did not significantly affect usefulness of the measurements. A significant positive correlation was seen between body weight and the femur BMC/W, indicating that the method accurately reflected expected physiological changes in bone mineral. The method is suitable for the rapid, simple, accurate, and reproducible measurement of bone mineral in the anesthetized rat and is applicable to serial measurements.

Animals↗

The proteinuria of diabetic nephropathy.

The results of an investigation into the nature of the proteinuria of diabetic nephropathy are described. Proteinuria increases quantitatively with deteriorating renal function but there is no consistent qualitative change; even with small amounts of proteinuria the selectivity may be poor and the proportion of albumin to the total excretion constant. These and other findings are discussed in relation to the possible pathogenesis of the glomerular dysfunction in diabetic nephropathy.

Adult↗

A streptomycin dependent live Pasteurella multocida vaccine for the prevention of rabbit pasteurellosis.

A culture of Pasteurella multocida was isolated from a rabbit exhibiting clinical signs of respiratory pasteurellosis. Organisms from this culture were incubated in the presence of the mutagen n-methyl-n'-nitro-n-nitrosoguandine in order to obtain a streptomycin dependent mutant. A live vaccine was prepared from this mutant, and healthy pasteurella-free rabbits were vaccinated either by intranasal or subcutaneous administration. Either method provided complete protection against homologous, wild-type challenge as evidenced by absence of clinical signs or gross pathology and failure to isolate the organism from mucous secretions of tissues from vaccinated individuals.

Animals↗

Noninvasive measurement of bone mineral mass in the unanesthetized rabbit.

Direct photon absorptiometry was used for the in vivo measurement of bone mineral mass in the rabbit tibia. Bone mineral mass in 124 male and female rabbits was correlated (p less than 0.001) with age to 26 weeks and weight to 5.5 kg. Examining reproducibility and repositioning error, three rabbits were measured 12 times each. Bone mineral mass in the three rabbits was: 0.432 +/- 0.020 g/cm2, 0.414 +/- 0.010 g/cm2 and 0.487 +/- 0.037 g/cm2. The greatest coefficients of variance observed for measurements without repositioning and measurements with repositioning were 4.8% and 7.6%, respectively. The technique provided sensitive, reproducible and noninvasive measurement of bone mineral mass without anesthesia or undue restraint.

Age Factors↗