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Biomedical subjects

L S Mullin

Publications and source records attributed to L S Mullin.

16 recordsLinked to original sources
PubMed1993

Investigation of a mechanism for Leydig cell tumorigenesis by linuron in rats.

In a previously conducted 2-year study, a concentration-dependent increase in Leydig cell adenomas was observed in Crl:CD BR(CD) rats fed diets containing the herbicide linuron. Linuron has been shown to be negative in a battery of six tests for genotoxicity; therefore, a nongenotoxic mechanism of tumorgenesis was investigated. Linuron is structurally related to the nonsteroidal antiandrogen, flutamide. Flutamide has also been shown to produce Leydig cell tumors within 1 year, presumably due to sustained hypersecretion of luteinizing hormone (LH) which occurs following disruption of the hypothalamic-pituitary-testicular (HPT) axis. To investigate whether linuron possesses antiandrogenic activity, sexually immature and mature CD rats were administered either 200 mg/kg linuron or 10 mg/kg flutamide (positive control) for 2 weeks. Accessory sex organs were weighed and serum hormone levels were measured to assess androgen status and alterations in the HPT axis. Serum from a multigeneration reproduction study with linuron was also analyzed for serum hormone levels. In addition, competitive receptor binding studies were conducted to evaluate the ability of linuron to bind to the androgen receptor. Linuron decreased accessory sex organ weights in sexually immature and mature linuron-treated rats. Increased serum estradiol and LH levels were observed in sexually mature linuron-treated rats. Serum estradiol and LH levels were also elevated in P1 and F1 male rats from the multigeneration reproduction study. These accessory sex organ and hormonal changes are consistent with those seen with the antiandrogen flutamide, the only exception being serum testosterone, which was elevated following exposure to flutamide but not to linuron. The inability of linuron to increase testosterone levels may reflect the lower potency of linuron as an antiandrogen compared with that of flutamide, which is a potent antiandrogen. Additionally, linuron competed with [3H]testosterone for binding to the androgen receptor. The IC50 data for competition to the androgen receptor suggest that linuron is approximately 3.5 times less potent than flutamide. These data are consistent with the effects seen with flutamide and demonstrate that linuron is a less potent antiandrogen than flutamide. Collectively, these data support the hypothesis that linuron produces Leydig cell tumors via an antiandrogenic mechanism where sustained hypersecretion of LH appears to be responsible for the development of Leydig cell hyperplasia and adenomas.

Age Factors↗
PubMed1990

Toxicology update isoparaffinic hydrocarbons: a summary of physical properties, toxicity studies and human exposure data.

The Isoparaffins covered in this manuscript are branched aliphatic hydrocarbons with a carbon skeleton length ranging from approximately C10 to C15. They are used in the manufacture of liquid imaging toners, paint formulations, charcoal lighter fluid, furniture polishes and floor clearners. Potential exposure exists in the petroleum, printing and paint industries. Isoparaffins have a very low order of acute toxicity, being practically non-toxic by oral, dermal and inhalation routes. However, aspiration of liquid isoparaffins into the lungs during oral ingestion could result in severe pulmonary injury. Dermally, isoparaffins have produced slight to moderate irritation in animals and humans under occluded patch conditions where evaporation cannot freely occur. However, they are not irritating in non-occluded tests, which are a more realistic simulation of human exposure. They have not been found to be sensitizers in guinea pig or human patch testing. However, occasional rare idiosyncratic sensitization reactions in humans have been reported. Instillation of isoparaffins into rabbit eyes produces only slight irritation. Several studies have evaluated sensory irritation in laboratory animals or odor or sensory response in humans. When evaluated by a standard procedure to assess upper airway irritation, isoparaffins did not produce sensory irritation in mice exposed to up to 400 ppm isoparaffin in air. Human volunteers were exposed for six hours to 100 ppm isoparaffin. The subjects were given a self-administered questionnaire to evaluate symptoms, which included dryness of the mucous membranes, loss of appetite, nausea, vomiting, diarrhea, fatigue, headache, dizziness, feeling of inebriation, visual disturbances, tremor, muscular weakness, impairment of coordination or paresthesia. No symptoms associated with solvent exposure were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1983

Guinea pig respiratory response to isocyanates.

Exposure to some isocyanates (e.g., toluene diisocyanate) has been associated with development of respiratory sensitization. In this study, guinea pig respiratory response to protein conjugates of isocyanatoethyl methacrylate (IEM) and isocyanatoethyl propionate (IEP) was evaluated. Guinea pigs were exposed to daily induction exposures with an aerosol of bovine serum albumin (BSA) or BSA conjugated with IEM or IEP. After approximately 2 weeks significant increases in respiratory rate occurred in the guinea pigs exposed to the isocyanate conjugates. The number of animals responding was related to the degree of conjugation of isocyanate to protein. No response to unconjugated BSA was observed. The isocyanates conjugated to another carrier, guinea pig serum albumin (GSA), elicited responses. In guinea pigs responding to BSA-IEM, 0.01 ppm IEM monomer did not elicit responses; 0.1 to 0.4 ppm IEM vapor elicited responses similar to conjugates but which were delayed; 0.5 and 0.6 ppm induced irritation responses. An IEM polymer aerosol that contained less than 0.004% monomer did not elicit a response. These data suggest a response threshold. Guinea pig developing responses to either of the isocyanate conjugates displayed cross-reactions to challenge with the other. A conjugate of BSA with hexyl isocyanate (HI) did not induce cross-responses in guinea pigs reactive to BSA-IEM. Application of BSA-IEP or IEP monomer to the scratched skin of guinea pigs that responded by inhalation to BSA-IEP resulted in immediate wheal and flare responses not seen in unexposed animals. All of these findings suggest induction of Type I hypersensitivity (asthmatic) directed toward the isocyanate portion of the conjugate and not the protein.

Acrylates↗
PubMed1983

Eye irritation response of humans to formaldehyde.

Human panelists sensitive to formaldehyde eye irritation were exposed to low concentrations of formaldehyde vapor (0.35 to 1.0 ppm) for 6 minutes. Eye irritation was evaluated by time to detection of the first trace of irritation and by subjective ranking of severity. Both time to response and severity appeared to be functions of formaldehyde concentration. Severity of response was above "slight" only with highest test concentration, 1.0 ppm.

Dose-Response Relationship, Drug↗
PubMed1982

Comparison of unconditioned reflex and conditioned avoidance tests in rats exposed by inhalation to carbon monoxide, 1,1,1-trichloroethane, toluene or ethanol.

The sensitivity of unconditioned reflex and conditioned avoidance tests in evaluating behavioral toxicity was compared. Male rats were exposed by inhalation up to four hours to 0, 200, 400, 800 or 1600 ppm carbon monoxide (CO); 0, 1500, 3000, 6000 or 12,000 ppm 1,1,1-trichloroethane; 0, 800, 1600, 3200, or 6400 ppm toluene; or 0, 4000, 8000, 16,000 or 32,000 ppm ethanol. Animals were tested for behavioral changes at one-half, one, two and four hours during exposure and eighteen hours after exposure ended. In unconditioned reflex testing the presence or absence of specific unconditioned reflexes (such as corneal, placing, grasping and righting reflexes) and simple behavior patterns including locomotor activity and coordination were observed. The conditioned reflex task consisted of shock avoidance by lever press following simultaneous light and sound stimuli. Rats began to fail unconditioned reflex tests at 800 ppm CO, 3000 ppm trichloroethane, 800 ppm toluene and 8000 ppm ethanol. Decrements in conditioned avoidance were observed at 800 ppm CO, 6000 ppm trichloroethane, 3200 ppm toluene and 8000 ppm ethanol. Neither test was consistently more sensitive than the other in detecting behavioral changes. For both methods, the concentrations at which changes were detected in rats were two to tenfold higher than those reported for human effects.

Animals↗
PubMed1979

Cardiac arrhythmias and blood levels associated with inhalation of Halon 1301.

In this study we determined airborne concentrations of Halon 1301 (CBrF3) and the associated blood levels which produce cardiac arrhythmias in dogs. Beagle dogs were exposed by inhalation to Halon 1301 concentrations ranging from 5 to 20% and, after five minutes of exposure, were given epinephrine by intravenous injection (8--10 micrograms/kg). Electrocardiograms were recorded. Serious cardiac arrhythmias were produced with concentrations of 7.5% or greater. A second group of dogs with cannulas surgically implanted in the common carotid artery and external jugular vein were exposed to 5%, 7.5% and 10% Halon 1301 for 60 minutes. The blood concentration of Halon 1301 increased rapidly during the first five minutes of exposure, plateaued within twenty minutes, and declined rapidly after exposure. The mean blood concentrations at equilibrium were directly proportional to airborne concentrations: at a concentration of 5% in air -- arterial 19.2 micrograms/mL, venous 14.6 micrograms/mL; at 7.5% in air -- arterial 30.6 micrograms/mL, venous 28.4 micrograms/mL; and at 10% in air -- arterial 402 micrograms/mL, venous 32.1 microgram/mL. Since there was no rapid increase in blood fluorocarbon concentration after the first five minutes of exposure, it does not seem likely that risk of cardiac sensitization would increase with increased length of exposure to a given concentration.

Air↗
PubMed1976

The effect of myocardial infarction on the cardiac sensitization potential of certain halocarbons.

We have previously shown that many halocarbons and hydrocarbons are capable of producing cardiac sensitization. Briefly, the test method involved exposure of healthy, unanesthetized, beagle dogs to various inspired levels of sensitizing agent, followed by an intravenous dose (8 mug/kg) of epinephrine. Along, this epinephrine dose produces only mild ECG alterations, but, at threshold levels of a sensitizing agent, may induce a serious cardiac arrhythmia and sometimes death. Using the same test protocol, dogs with experimentally-induced myocardial infarctions were used to determine whether this type of heart condition might significantly lower the threshold for cardiac sensitization. Test results on three halocarbons showed no greater potential for cardiac sensitization among dogs having recovered from myocardial infarction as compared to normal, healthy animals.

Animals↗