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Biomedical subjects

J L Mattsson

Publications and source records attributed to J L Mattsson.

At least 19 recordsLinked to original sources
PubMed1992

Abnormal auditory brainstem responses and cochlear pathology in rats induced by an exaggerated styrene exposure regimen.

Groups of 12 male 42-day-old rats were exposed to 0 or 800 ppm styrene vapors for 14 hr/day, 5 days/week for 3 weeks. Tone-pip auditory brainstem responses (ABRs) at 4, 8, 16, and 30 kHz were obtained after the last exposure. ABRs were minimally affected at 4 kHz and moderately to severely affected at 8, 16, and 30 kHz as indicated by waveforms which had a decreased amplitude and increased latency as compared to the controls. Missing outer hair cell(s) were evident in the basal and lower middle turns of the organ of Corti. Outer hair cell loss was least in the first row and greatest in the second and third rows. Occasional inner hair cells were also missing in regions of severe outer hair cell loss. The distribution of hair cell loss within the cochlea was consistent with the pattern of ABR alterations. These data document mid-frequency auditory dysfunction in styrene-exposed young adult rats with significant damage to the organ of Corti following an exaggerated styrene exposure regimen.

Animals↗
PubMed1990

Neurotoxicologic evaluation of rats after 13 weeks of inhalation exposure to dichloromethane or carbon monoxide.

Male and female Fischer 344 rats were exposed to dichloromethane (methylene chloride, DCM) or carbon monoxide (CO) for 6 hr/day, 5 days/week, for 13 weeks. Since oxidative metabolism of DCM to CO and CO2 is a saturable process, DCM exposure concentrations were selected clearly below saturation (50 ppm), just below saturation (200 ppm), and well above saturation (2000 ppm). At saturation of metabolism, metabolic CO causes about 10% carboxyhemoglobinemia (COHb). Therefore, as a control for CO effects, a separate group of rats was exposed to 135 ppm CO to induce approximately 10% COHb. Postexposure functional tests included an observational battery, hindlimb grip strength, and a battery of evoked potentials (flash, auditory brainstem, somatosensory, caudal nerve). After functional tests were completed, rats from all groups were perfused with fixative and a comprehensive set of nervous tissues from the high DCM exposure group and from controls were examined by light microscopy. Although some miscellaneous functional and morphologic variations were recorded, none were related to treatment. Thus, subchronic exposures as high as 2000 ppm DCM or 135 ppm CO had no deleterious effects on any of the measures of this study.

Action Potentials↗
PubMed1990

Evoked potential changes from 13 weeks of simulated toluene abuse in rats.

Fischer 344 rats were exposed to 8000 ppm toluene vapor in an 'abuse' paradigm for 13 weeks to develop an animal model for 'solvent neurotoxicity.' Exposures to toluene were multiple and short (15 to 35 min), adjusted according to tolerance. Although body weight was reduced 23% from controls, the toluene-exposed rats appeared healthy. Evoked potentials taken postexposure were, however, mildly to severely affected. Flash-evoked potentials were slow and topographically disorganized; 10 kHz tone-pip auditory brainstem responses (ABRs) had severe loss of power and loss of detail. Click and 30 kHz ABRs, somatosensory-evoked potentials, and caudal nerve action potentials were less affected. No neuropathologic changes were detected by light microscopy (perfusion fixation, special stains). Thus, postexposure multimodal functional effects were readily detected after subchronic, severe episodic exposures to toluene.

Action Potentials↗
PubMed1990

Screening for neurotoxicity: complementarity of functional and morphologic techniques.

Our philosophy is that screening tests should be applicable across species and emphasize complementarity to neuropathology. Within this context, electrophysiological tests comparable to those in human clinical neurology are powerful screening tools. For example, while histopathologic evaluation of the cochlea for ototoxicity is difficult, evoked potential audiometry is fast and easy. In this instance, one might routinely screen for deficits in auditory function, and reserve morphologic techniques for a characterization role rather than one of discovery. Lesions of neurons, axons and myelin are, however, readily assessed by light microscopy. A suitable combination of functional and morphologic screening tests, therefore, enhances the ability to discover neurotoxicity, and these data often are ideal for generation of refined hypotheses for subsequent characterization studies.

Animals↗
PubMed1990

Spontaneous lesions in subchronic neurotoxicity testing of rats.

Male and female Fischer 344 rats, 30 weeks of age, were examined for neuropathologic changes after a 13-week inhalation neurotoxicologic study. Tissues were preserved by whole-body perfusion with 1.5% glutaraldehyde/4% formaldehyde solution. An extensive set of neural tissues was embedded in paraffin, sectioned, and stained with hematoxylin and eosin, luxol fast blue/periodic acid-Schiff/hematoxylin, Sevier-Munger silver, and cresyl echt violet. Lesions in the central and peripheral nervous system were comparable between sexes and between control and treated animals. Bilateral swollen axons were present in the medial aspect of the nucleus gracilis adjacent to the area postrema. Occasional swollen axons also were observed in the dorsal and ventral funiculi of the spinal cord. Degeneration of individual nerve fibers was present in the trapezoid body, vestibular nerve root, trigeminal nerve, cerebellar peduncles, and the funiculi of the spinal cord. Individual nerve fiber degeneration also was present in the spinal nerve roots, sciatic and tibial nerves. Nerve fiber degeneration was characterized by myelin disruption and degeneration, vacuoles and axonal fragmentation. Similar spontaneous neuropathology may be encountered in rats from other subchronic neurotoxicologic studies and must be differentiated from treatment-related toxicity.

Administration, Inhalation↗
PubMed1990

The improbable association between the herbicide 2,4-D and polyneuropathy.

Isolated case reports have circumstantially linked the use of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) to polyneuropathy. However, a critical review of the literature reveals numerous reasons for doubting a relationship of 2,4-D to polyneuropathy: (1) too few cases given the wide use of the chemical; (2) no valid toxicologic or epidemiologic evidence; (3) the diversity of antecedent illness; (4) an unlikely time sequence of antecedent illness to exposure (pharmacokinetics); (5) the lack of polyneuropathy in medical patients given repetitive doses of 2,4-D; (6) the lack of polyneuropathy in heavily exposed military personnel involved in operation Ranch Hand; (7) the biological properties of 2,4-D which minimize penetration of 2,4-D into the nervous system under normal exposure conditions; and (8) the lack of polyneuropathy in a variety of experimental animal species given 2,4-D by several routes of exposure and at dose levels and durations of exposure many times greater than human applicator exposure. Thus, the weight of evidence indicates that 2,4-D is an unlikely cause of polyneuropathy.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1989

Critical assessment of motor activity as a screen for neurotoxicity.

Motor activity consists of a large number of motor behaviors not placed under stimulus control. The Environmental Protection Agency defines motor activity in terms of "activity counts," and has incorporated it in the guidelines for the assessment of neurotoxicity. While motor activity testing has some enticing operating characteristics, a dose-related change in activity counts can reflect an effect on the nervous system only in the absence of systemic toxicity. Furthermore, when a motor activity effect has been documented, ancillary data or further testing is needed to determine whether this effect is indeed adverse. In addition, the results of a motor activity test do not usually provide information about either the origin of the problem, or the follow-up tests that need to be conducted.

Animals↗
PubMed1986

Incapacitation and treatment of rats exposed to a lethal dose of sulfuryl fluoride.

Rats exposed to 4000 ppm sulfuryl fluoride (VIKANE gas fumigant, SO2F2) were incapacitated within 45 min and died within several hours after exposure. Exposure to higher concentrations resulted in a shorter time to incapacitation and death occurred within minutes. Treatment with calcium gluconate before exposure to 4000 ppm SO2F2 for 45 min resulted in 80% survival. However, calcium gluconate did not alleviate SO2F2-induced convulsions. Administration of phenobarbital before or after exposure to 4000 ppm SO2F2 for 45 min effectively reduced the frequency and severity of convulsions and resulted in survival of all animals. Exposure of rats to 10,000 ppm SO2F2 for 15 min followed by treatment with phenobarbital reduced the frequency of convulsions and delayed death, but did not prevent death. Diazepam was less effective than phenobarbital while diphenylhydantoin had no beneficial effect and, in fact, made the convulsions more severe and longer in duration. The results of this study indicate that phenobarbital was effective in ameliorating the acute toxic effects of an overexposure to SO2F2 in rats.

Animals↗
PubMed1986

Lack of neuropathologic consequences of repeated dermal exposure to 2,4-dichlorophenoxyacetic acid in rats.

A 24% aqueous solution of the dimethylamine salt of 2,4-dichlorophenoxyacetic acid (2,4-D amine) was applied to the legs of male Fischer 344 rats 2 hr/day, 5 days/week, for 2 weeks. Because this concentration caused severe skin lesions, a second group of rats was treated similarly with a 12% solution of 2,4-D amine for 3 weeks. The 12% solution caused only mild skin changes. The plasma 2,4-D content, at the end of exposure, was nearly five times greater in the rats exposed to the 24% solution than to the 12% solution (323 vs 66.5 micrograms/ml). The severe skin changes probably facilitated absorption in the rats treated with the 24% solution. Rats treated with either concentration weighed less than controls. Although histologically normal, kidneys of treated rats weighed more than controls. The increased kidney weights were attributed to physiological adaptation due to active excretion of absorbed 2,4-D. Light microscopic examination of tissues, other than skin, revealed no differences between treated and control animals. There were no nervous system pathologic changes although the rats were exposed to sufficient amounts of 2,4-D amine to cause severe skin lesions, decreased body weights, and increased kidney weights.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1985

Neurotoxicity of methyl chloride in continuously versus intermittently exposed female C57BL/6 mice.

This study evaluated the relationship between methyl chloride (MeCl) exposure duration and neurotoxicity. Female C57BL/6 mice were exposed to MeCl for 11 days, either continuously (22 hr/day) to 15, 50, 100, 150, or 200 ppm, or intermittently (5.5 hr/day) to 150, 400, 800, 1600, or 2400 ppm. This strain and sex of mouse was chosen because it is sensitive to MeCl neurotoxicity and was a good candidate to allow the evaluation of morphological effects and the quantitation of functional effects. A simple quantitative relationship between neurotoxicity and continuous vs intermittent exposure was not observed. Although the no-observable-effect levels for continuous and intermittent MeCl exposures were very nearly proportionate to exposure concentration multiplied by duration, the dose-response curve was much steeper for continuously exposed mice. Cerebellar granular cell layer degeneration was observed in mice exposed continuously to 100 ppm MeCl and in mice exposed intermittently to 400 ppm. This histopathologic effect was observed at lower concentrations than a decrement in rotating rod running performance. No effects were observed in mice exposed to 50 ppm continuously or to 150 ppm intermittently. Continuous exposure to MeCl produced the cerebellar lesion with less effect on other tissues than did intermittent exposure. In mice exposed to 2400 ppm intermittently, there were renal and hematopoietic effects in addition to relatively slight cerebellar granular cell layer degeneration. These 2400-ppm exposed mice developed hemoglobinuria, apparently as a result of intravascular hemolysis. Although the effect of exposure duration on MeCl toxicity was complex, this study indicated that careful judgment is necessary when extrapolating intermittent exposure data to a continuous exposure situation.

Animals↗
PubMed1985

Subchronic oral toxicity, tissue distribution and clearance of hexachloroethane in the rat.

Hexachloroethane (HCE) was fed to Fischer 344 rats at approximate doses of 0, 1, 15 or 62 mg/kg/day for 16 weeks. Selected tissues were assayed at termination for HCE content. Histopathological examination identified the kidney as the primary target organ with male rats more sensitive than female rats. The kidney concentration of HCE increased proportionately with dose in the males, but there were disproportionately small increases with dose in females. A group of male rats was given 62 mg/kg/day for 8 weeks to estimate tissue clearance. Clearance of HCE from fat, liver, kidney and blood occurred in an apparent first-order manner with a half-life of approximately 2.5 days. The apparent first-order elimination suggests that HCE metabolism and excretion were not saturated in rats given up to 62 mg/kg/day and suggests that, in the range of doses given, toxicity should be proportional to exposure concentration. The no-observable-effect level (NOEL) for toxicity was 1 mg/kg/day for male and female rats.

Administration, Oral↗
PubMed1984

H-reflex waveform and latency variability in rats.

The right tibial nerve of each of 11 anesthetized male Fischer 344 rats was electrically stimulated at the ankle, and H-reflexes were recorded simultaneously from four locations in the hind foot. Needle electrodes were used for stimulating and recording. The mean (+/- SD) latency to the dominant peak of the H reflex was 10.21 +/- 0.75 msec. Individual rats had a 10% difference in latency from the "fastest" to the "slowest" locations in the foot, although any of the four locations could produce the fastest (shortest latency) response. The H reflexes varied from simple, single peak waveforms to complex multiple peak waveforms. The dominant peak polarity was unpredictably either positive or negative. These variations in complexity and latency occurred among rats and among the four locations within an individual rat. The dominant peak was identified in complex waveforms by adjusting the stimulating intensity and by recording from more than one location in the foot. The smallest coefficient of variation (5.57%) resulted from selecting data from the fastest electrode locations.

Action Potentials↗
PubMed1984

Prevention of radiation emesis in dogs by combinations of drugs.

Male mixed-breed dogs were used to evaluate the effectiveness of cimetidine (Cim), promethazine (Pro), and thiethylperazine (Thi), singly and in combination, to raise the threshold for radiation-induced emesis. Cim was chosen as an H2 antihistamine, Pro as an H1 antihistamine, and Thi as a phenothiazine derivative dopamine blocker. Doses were: 167 mg/m2 i.v. for Cim; 13.9 mg/m2 i.m. for Pro; and 5.6 mg/m2 i.m. for Thi. These doses were calculated on a mg/m2 basis to approximate doses for an average human (1.8 m2) of 300 mg Cim, 25 mg Pro, and 10 mg Thi. Exposure was to 60Co at 60 rad (midline) per min. The dogs were fed 0.4 kg canned dog food 1 hour before exposure, and injected with the appropriate drugs 30 minutes prior to exposure. Emesis onset times, number of episodes, and time to last episode were recorded. The radiation dose (midline tissue rad) to cause a 50% incidence of emesis (ED50) was calculated using an up-and-down procedure. The ED50 (95% confidence limits) were: 258 (212-315) for controls; 240 (151-380) for Cim; 313 (256-384) for Pro; 405 (319-514) for Thi; 334 (284-394) for Cim + Pro; 446 (365-546) for Cim + Thi; 347 (306-399) for Pro + Thi; and 478 (428-539) for Cim + Pro + Thi.

Animals↗
PubMed1982

Effects of benactyzine on an equilibrium and multiple response task in rhesus monkeys.

Five Macaca mulatta were tested for performance changes following exposure to benactyzine HCl (intramuscular) at four doses ranging from 0.054 mg/kg to 1.7 mg/kg. Subjects simultaneously operated a primate equilibrium platform and responded to a multiple alternative reaction task. Performance on both the continuous and discrete tasks were progressively degraded as benactyzine dose increased. At the higher doses it appeared that they concentrated their efforts on one of the tasks while neglecting the other. Thus, performance on one task might be normal and at the same time performance on another task would be degraded.

Animals↗
PubMed1981

Early effects of methylmercury on the visual evoked response of the dog.

A disturbing characteristic of methylmercury (MeHg) intoxication is the preclinical "silent" stage. This stage is followed by the sometimes rapid onset of clinical signs such as peripheral sensory loss, motor difficulties, and visual and auditory impairment. The objective of this study was to search for "preclinical" changes in the electrophysiological activity of the central nervous system of dogs exposed to methylmercury chloride. Because of the prominence of the visual system in the MeHg literature, the visual evoked response (VER) was selected for evaluation. A dose rate of 500 microgram/kg/day po was expected to cause clinically apparent toxicosis in about 2 mon. After 1 week of exposure, a subtle distortion of the VER occurred. In a parallel group of dogs, blood mercury was 0.74 microgram/ml at this time, and brain mercury content was 1.28 microgram/g at the occipital cortex. Although the dogs continued to receive MeHg, VERs remained remarkably stable for the next 5 to 8 weeks, and then rapidly degraded during the nest few days as the dogs exhibited visual and motor disabilities. In many species, when brain Hg is about 15 microgram/g, clinical and histopathologic changes are usually present, and may even be detected at 8 microgram/g. Distortion of the VER at 1.28 microgram/g Hg at the visual cortex demonstrates that CNS changes exist during the "silent" stage of toxicosis, and at a brain Hg content suggesting physiologic dysfunction of neurons rather than neuronal death.

Animals↗
PubMed1981

Acute and chronic propylene glycol dinitrate exposure in the monkey.

Rhesus monkeys (Macaca mulatta) were exposed to propylene glycol 1,2-dinitrate (PGDN) vapors on either an acute (4-h) or chronic (125-d) schedule. During acute exposures, PGDN concentrations ranged from a low of 2 ppm (parts per million) to a high of 33 ppm. Free operant avoidance behavior and visual evoked responses were monitored and free operant avoidance was not affected at any dose level. The late positive (100-150 ms) wave of the visual evoked response increased 20% at 2 ppm and decreased 25% at concentrations up to 33 ppm. Although these changes were statistically different from control values, they were within the limits caused by distracting events (+/-40%), and might possibly have been caused by the irritating or distracting properties of the vapor. Other monkeys were exposed to successively increasing concentrations of PGDN vapors at 0.3-4.2 ppm. 23 h/d, for 125 d. Daily performance testing included alternating sessions of discrete-trial cued avoidance and free operant avoidance. Non of the PGDN concentrations had a discernible effect on either type of avoidance performance.

Animals↗
PubMed1981

Radiation and G tolerance in rats.

Male hooded rats were exposed to 2100 rad 60Co radiation and 18 h later were exposed to +Gz acceleration until heart rate was reduced to 50% of baseline rate. G tolerance was 9.2% less in irradiated rats than in controls. Although small, this difference was significant at p less than 0.05. A similar group of rats was anesthetized 18 h postirradiation and carotid mean arterial pressures were measured. Mean arterial pressure was 122.1 torr for controls and 114.5 for irradiated. This difference was not significant.

Acceleration↗