Subacute toluene exposure increases DA dysfunction in the 6-OH dopamine lesioned nigrostriatal dopaminergic system of the rat.

The potential neurotoxicity of the solvent toluene to the nigrostriatal dopaminergic system was assessed in a rat model of Parkinson's disease. Rats, 1 day after a unilateral injection of 6-hydroxydopamine (6-OH DA) into the substantia nigra, inhaled air or different concentrations of toluene (80, 300 or 1000 ppm), 6 h/day for 3 days. The animals were sacrificed 2 days after the last exposure and biochemical measurements of catecholamines and 3,4-dihydroxyphenylacetic acid (DOPAC) were performed in the neostriatum and substantia nigra. Toluene at 80 and 1000 ppm significantly enhanced the depletion of striatal DOPAC levels induced by the lesion and produced at 80 and 300 ppm a trend for intensifying the 6-OH DA-induced depletion of striatal DA stores. The alterations induced after the combined challenge to the dopaminergic nigrostriatal system may reflect endangering actions of toluene.

Extracellular dopamine levels within the striatum increase during inhalation exposure to toluene: a microdialysis study in awake, freely moving rats.

An exposure chamber for microdialysis on awake, freely moving rats during exposure to volatile agents is described. Inhalation exposure to 1000 and 2000 ppm toluene for 2 h was accompanied by an increase in extracellular dopamine levels within the striatum, but did not affect the homovanillic acid level. Neither the dopamine nor the homovanillic acid level was affected by toluene 500 ppm or isoamylacetate. It is suggested that the action of inhaled toluene on the dopamine neuron differs from that of the anaesthetic halothane, possibly by interfering with dopamine reuptake. Microdialysis seems to be a useful tool for studying the effects of volatile agents on brain neurotransmission.

Acute toluene exposure increases extracellular GABA in the cerebellum of rat: a microdialysis study.

Effect of acute inhalation exposure of toluene or halothane anaesthesia on extracellular levels of gamma-aminobutyric acid (GABA) was monitored within the cerebellum of rats by microdialysis. GABA increased during and after exposure to toluene (2000 p.p.m., 2 hr) in contrast, halothane had no noticeable effect on GABA levels. When tetrodotoxin was added to the perfusion medium basal concentrations of GABA decreased to about 74% of control concentrations. Extracellular GABA levels did not increase during exposure to toluene when tetrodotoxin was added to the perfusion medium. The results indicate that toluene increase GABA within the cerebellum by sodium dependent mechanisms, possibly by modulating the neuronal input from the mossy fibers to the cerebellar cortex.

Effect of exposure to 2,5-hexanediol in light or darkness on the retina of albino and pigmented rats. I. Morphology.

Male albino (Sprague Dawley) and pigmented (Norwegian Brown) rats received 1% 2,5-hexanediol (H) in their drinking water for 5 or 8 weeks, respectively. The rats were housed either in 12 h light (average 30 cd/cm2 inside cage) and 12 h darkness (group LH) or in total darkness (group DH). Two control groups (Light only, LC; Darkness only, DC) were studied in parallel under identical conditions. The animals were sacrificed at the end of H exposure or after an ensuing 13-week period without H but under the same lighting conditions. The retinas of albino rats in the LH group showed a reduction (compared to the LC, DH and DC groups) in the number of nuclei per unit area of the outer nuclear layer (ONL; p < 0.05) and degeneration of the outer segment and the inner segment layers (photoreceptor cells). A less pronounced loss of nuclei was seen in the LC group. No decrease in the number of nuclei, or signs of degeneration, were demonstrated in the albino DH or DC groups. Thirteen weeks after exposure to H, the albino LH rats had lost about 50% of the nuclei in the ONL (p < 0.05) and the outer plexiform layer (OPL) had almost disappeared. At the corresponding time, in the pigmented rats the LH and DH groups differed from the LC and DC groups. The degenerative process resulted in no inflammatory changes in the retina. The results imply an interaction exceeding simple summation after exposure to light and H, in destroying photoreceptors and OPL (p < 0.001) in albino rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of exposure to 2,5-hexanediol in light or darkness on the retina of albino and pigmented rats. II. Electrophysiology.

Albino (Sprague-Dawley) and pigmented (Norwegian Brown) male rats were exposed to 2,5-hexanediol (H; 1%) in their drinking water for 5 or 8 weeks, respectively. Half of the rats of each strain were housed in light (average 30 cd/cm2 inside cage, 12 h/day); the other half was kept in constant darkness. Control groups were studied in parallel under identical conditions but without H. Electrophysiological recordings were made 2-5 days and 13 weeks after the end of the exposure to H. Alterations in the visual system, as measured by electroretinography and visual evoked response, were found in groups of albino rats exposed to H and/or light. The pupillary diameter was enlarged in the albino group exposed to both H and light. Among the pigmented rats, alterations were recorded only in the visual evoked response of the H exposed groups. The results demonstrate that simultaneous exposure to H and light can lead to alterations in visual function that are more severe than those induced by each agent alone, and may exceed a simple summation.

Children of male spray painters: weight and length at birth.

The course and outcome of the pregnancies of the wives of 80 spray painters and 80 electronics workers were recorded from birth registers, hospital records, and a questionnaire. The two groups of men had previously been subjected to psychological, psychiatric, neurophysiological, and neurological tests. The variables recorded were occupational exposure to solvents; number of births, ectopic pregnancies, and miscarriages; weight, length, and malformations of the newborn children; duration of the pregnancies; birth complications; and neonatal hospital treatment. The mean length and weight of the children of spray painters at birth were slightly lower than those of the children of electronics workers. No differences were recorded for serious complications of pregnancy, malformations, or clinical course after birth.

Auditory degeneration after exposure to toluene in two genotypes of mice.

Two inbred strains of mice, CBA/Ca (with a moderate hearing loss starting late in life) and C57BL/6J (with an early onset of spontaneous auditory degeneration), were exposed to toluene by inhalation (1000 ppm, 12 h/day, 7 days) at either 1 or 6 months of age. Thresholds of auditory brainstem response (ABR) were measured 3-5 days after exposure and assessed repeatedly up to the age of 16 months (C57) or 23 months (CBA). Both strains of mice exposed to toluene at 1 month of age showed a mild loss of sensitivity at a high frequency (31.5 kHz) shortly after exposure. With increasing age, toluene exposure had little effect on the aging process of the auditory system in CBA mice but accelerated age-related hearing loss in C57 mice. The results indicate that toluene exposure can aggravate auditory deterioration only in mice with a strong genetic predisposition to spontaneously precocious age-related hearing loss.

Long-term effects of toluene inhalation on rat behavior.

The effect of inhalation exposure to toluene (3700 mg/m3, 1000 ppm, 21 h/day, 5 days/week, during 4 weeks) on male Sprague-Dawley rats was tested. A wide range of test situations was used, including an operant test with baseline performance and extinction, motor coordination, and exploratory activity. All tests were made 11 to 35 days after the end of the exposure. The results indicate that toluene exposure causes a long-lasting impairment on the extinction process and reduction in the variability of the baseline response in the operant behavior situation. Toluene also had an effect on the water regulation.

Vestibular-oculomotor, opto-oculomotor and visual function in the rat after long-term inhalation exposure to toluene.

Pigmented rats were exposed to toluene (1000 ppm, 21 h/day) for 6 or 11 weeks. The function of the vestibulo- and opto-oculomotor systems was tested one month after the end of the exposure by recording of nystagmus, induced by vestibular or optokinetic stimuli. The eye movements were recorded by a magnetic search coil technique. The optokinetic gain in the exposed animals was reduced compared to a control group. There was also a slight reduction in gain during sinusoidal oscillatory vestibular stimulation. No effect of the toluene exposure on the gain or duration of nystagmus during acceleratory or deceleratory rotatory stimulation was demonstrated, nor was there any change in the duration of the optokinetic after-nystagmus. The function of the visual system was tested 2 to 5 days after exposure by recording the electroretinogram and the visual evoked response. The conduction velocity in peripheral nerve was also measured. No effect of the toluene exposure on these variables was seen. The results indicate that long-term inhalation of toluene causes a long-lasting, possibly permanent, lesion within the vestibulo-cerebellum. They gave no evidence that such exposure affects peripheral vestibular or visual function.

Sequence of exposure to noise and toluene can determine loss of auditory sensitivity in the rat.

Rats were exposed to noise (100 dB Leq, 10 h/d, 7 d/w, 4 w), or to toluene (1,000 ppm, 16 h/d, 7 d/w, 2 w), or to noise followed by toluene. Auditory sensitivity was tested before exposure, and 1 to 4 weeks after exposure, by brainstem audiometry using a 1/3-octave filtered sine wave stimulus at the frequencies 1.6, 3.15, 6.3, 12.5 and 20.0 kHz. Some auditory impairment was observed after all exposures. The sensitivity loss after exposure to noise followed by toluene was greater than that recorded after exposure to noise alone or toluene alone, but did not exceed the summated loss caused by noise alone and toluene alone at any frequency. This result contrasts with the earlier reported effect of the same exposures in the reversed order. It is concluded that the exposure sequence can determine the extent of auditory impairment.

Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to n-hexane and a protective effect of simultaneous exposure to toluene or xylene.

Testicular and germ cell line morphology in rats were studied 2 weeks, 10 months and 14 months after cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgen biosynthetic capacity of testis, testosterone blood concentration, vas deferens morphology and noradrenaline (NA) concentration, epididymal sperm morphology, and fertility were also studied. Severe testicular atrophy involving the seminiferous tubules with loss of the nerve growth factor (NGF) immunoreactive germ cell line was found. Total loss of the germ cell line was found in a fraction of animals up to 14 months post-exposure, indicating permanent testicular damage. No impairment of androgen synthesis or androgen dependent accessory organs was observed. Simultaneous administration of 1000 ppm n-hexane and 1000 ppm toluene, or 1000 ppm n-hexane and 1000 ppm xylene, did not cause germ cell line alterations or testicular atrophy. Toluene and xylene were thus found to protect from n-hexane induced testicular atrophy.

Effect of interaction between noise and toluene on auditory function in the rat.

Rats were exposed to toluene (1000 ppm, 16 h/d, 5 d/w, 2 w), or noise (100 dB Leq, 10 h/d, 7 d/w, 4 w) or toluene followed by noise. Auditory function was tested by brainstem audiometry using a 1/3 octave filtered sine wave stimulus at the frequencies 1.6, 3.15, 6.3, 12.5 and 20.0 kHz. A high-frequency auditory impairment was observed after exposure to toluene alone and noise alone. A slight recovery was recorded 1 and 6 months after the toluene exposure. Toluene followed by noise resulted in a higher threshold at all frequencies. A slight recovery was recorded 6 months post-exposure. The threshold shift exceeded the summated loss caused by toluene alone and by noise alone, particularly at 3.15 and 6.3 kHz. The latencies varied only slightly. The results indicate that the major cause of the auditory impairment was cochlear damage and that only minor injury was caused to the auditory pathways.

Photoreconvertible fluorophore systems in rhabdomeres, Semper cells and corneal lenses in the compound eye of the blowfly.

1. The primary aim of the experiments described in this article was to localize the origin of the complex fluorescence in the compound eye of flies. The eye tissue was dissected and the fluorescence from cells and cell organelles was recorded by microspectrofluorometry. Using this technique, fluorophore systems were detected in the rhabdomeres, Semper cells and corneal lenses. The fluorophore systems are photoreconvertible by UV and blue light. 2. The fluorophore systems in the rhabdomeres and Semper cells are similar. The intensity of the fluorescence from the microvilli is enhanced up to 29 X by adaptation to UV light. The enhancement is inversely related to the rhodopsin content in the microvilli, indicating that the chromophoric group of the fluorophore is not a vitamin A derivative. 3. The enhancement of the fluorescence by UV light strongly depends on pH, suggesting that the photoreconvertible fluorophore systems in the microvilli and Semper cells are photosensitive redox pigments. These redox systems are probably located in the membranes of the microvilli in the photoreceptors, and in the endoplasmic reticulum of the Semper cells, or they are coupled to filaments in the cytoskeleton of both cell types. 4. Preliminary reaction schemes for the photoreactions based on the recorded excitation and emission spectra and photokinetics were developed. A primary pigment in the microvillous structure, AR, or in organelles in the Semper cells, AS, is converted by UV light into an excited state AR* or AS*, which either relaxes to the primary pigment by photon emission, or converts into an intermediate X, which by proton uptake changes into stable products, BR or BS. Blue illumination converts BR and BS into the excited states BR* and BS*, which either relax by photon emission to BR or BS, or convert into an intermediate Y, which after deprotonation reconverts into the primary pigment AR or AS. 5. Estimation of the molecular density showed that the concentration of the fluorophore in the microvilli presumably is almost equal to maximal rhodopsin concentration. The high density suggests that the fluorophores have a specific function in transduction or adaptation of the visual process.

Visual pigment and visual receptor cells in fetal and adult sheep.

The visual pigments, and the structure of the visual cells, were investigated by spectrophotometry and by light and electron microscopy in fetal and adult sheep. The rhodopsin system in adult sheep closely resembles that of cattle. The absorbance maxima of rhodopsin, lumirhodopsin, and metarhodopsin I are at 498, 490, and 480 nm, respectively. The estimated molar absorbance coefficient at the wavelength of maximum absorption of rhodopsin is 40,000M-1 . cm-1. Rhodopsin was detected from a fetal age of 85 days (term at 145 days). Partial bleaching of extracts from fetal eyes (95, 105, and 115 days) did not demonstrate cone pigments, although cones were present in fair numbers at a fetal age of about 105 days. The time course of rhodopsin formation between 85 and 140 days resembles a growth curve. The amount of rhodopsin shortly before birth (140 days) is about 0.6 times that in the adult. The number and dimensions of rod outer segments as well as packing of the discs were studied structurally and related to the rhodopsin content. A fairly good correlation was found at the earliest stages (95 and 105 days gestation age), when rhodopsin concentration was very low and rod outer segments were few and small, as well as at the latest stage (140 days). At 115 days the rhodopsin content observed by spectrophotometry was less than that indicated by the outer segment volume, probably mainly due to the outer segment discs and possibly to the rhodopsin molecules being less tightly packed than at 140 days.