Hans Muijser

Exposure, Health and Ecological Effects Review of Engineered Nanoscale Cerium and Cerium Oxide Associated with its Use as a Fuel Additive

Advances of nanoscale science have produced nanomaterials with unique physical and chemical properties at commercial levels which are now incorporated into over 1000 products. Nanoscale cerium (di) oxide (CeO2) has recently gained a wide range of applications which includes coatings, electronics, biomedical, energy and fuel additives. Many applications of engineered CeO2 nanoparticles are dispersive in nature increasing the risk of exposure and interactions with a variety of environmental media with unknown health, safety and environmental implications. As evident from a risk assessment perspective, the health effects of CeO2 nanoparticles are not only dependent on their intrinsic toxicity but also on the level of exposure to these novel materials. Although this may seem logical, numerous studies have assessed the health effects of nanoparticles without this simple but critical risk assessment perspective. This review extends previous exposure and toxicological assessments for CeO2 particles by summarizing the current state of micro and nano-scale cerium exposure and health risks derived from epidemiology, air quality monitoring, fuel combustion and toxicological studies to serve as a contemporary comprehensive and integrated toxicological assessment. Based on the new information presented in this review there is an ongoing exposure to a large population to new diesel emissions generated using fuel additives containing CeO2 nanoparticles for which the environmental (air quality and climate change) and public health impacts of this new technology are not known. Therefore, there is an absolute critical need for integrated exposure and toxicological studies in order to accurately assess the environmental, ecological and health implications of nanotechnology enabled diesel fuel additives with existing as well as new engine designs and fuel formulations.

The effects of occupational exposure to styrene on high-frequency hearing thresholds☆

Subchronic exposure to styrene has been reported to produce high-frequency hearing loss in rats. In humans, hearing thresholds for higher frequencies (greater than 8 kHz) are also more vulnerable to ototoxic drugs than those at lower frequencies. Since hearing loss at frequencies above 8 kHz does not seem to play a role in speech processing, hearing loss at frequencies above 8 kHz in workers exposed to styrene or other solvents might easily escape detection. Therefore, hearing thresholds were evaluated at frequencies up to 16 kHz in workers exposed to styrene and compared to those of a control group of unexposed workers. The airborne concentrations of styrene typically did not exceed 150 mg/m3 although individual exposures did, at times, reach higher values (up to 700 mg/m3). In accordance with the literature, an age-dependent increase in hearing thresholds at high frequencies was found. Compared to controls, workers exposed to styrene did not appear to demonstrate an aggravated age-dependent decrease in hearing high frequencies. A comparison, however, within the experimental group between the least exposed and the most exposed workers revealed a statistically significant difference on hearing thresholds at high frequencies.

Mid-frequency hearing loss and reduction of acoustic startle responding in rats following trichloroethylene exposure.

Modification of auditory evoked startle responding using prepulse inhibition was used to examine the effects of trichloroethylene (TCE) exposure on auditory thresholds. Rats were exposed by inhalation to 0, 1500, or 3000 ppm TCE for 18 hours per day, 5 days a week for 3 weeks. Auditory thresholds for 5 and 20 kHz tones were measured before exposure and at 1, 3, and 6 weeks postexposure. In addition, hearing thresholds for 5 and 35 kHz tones were examined at a 5-week postexposure time-point. Results indicated that hearing thresholds for 20 kHz but not for 5 or 35 kHz prepulses were significantly increased in rats exposed to 3000 ppm TCE. These findings demonstrate a selective hearing loss in the 20 kHz range by short-term, high-level TCE exposure. With respect to effects on startle responding per se, the present study also found that compared to controls, TCE-exposed rats failed to show an increase in baseline startle with repeated testing. This difference could not be attributed to differences in body weight and was persistent throughout the postexposure period.

Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss.

Rats were exposed to ethyl benzene at 0, 300, 400 and 550 ppm for 8 hours/day for 5 consecutive days. Three to six weeks after the exposure, auditory function was tested by measuring compound action potentials (CAP) in the frequency range of 1-24 kHz and 2f1-f2 distortion product otoacoustic emissions (DPOAEs) in the frequency range of 4-22.6 kHz. In addition, outer hair cell (OHC) loss was quantified by histological examination. The lowest concentration ethyl benzene had no effect on any of the above measures. At 400 ppm, auditory thresholds were increased by 15 and 16 dB at 12 and 16 kHz, respectively, and at 550 ppm by 24, 31, and 22 dB at 8, 12, and 16 kHz, respectively. DPOAE amplitude growth with stimulus level was affected only after 550 ppm at 5.6, 8, and 11.3 kHz. OHC loss was found in two of the five examined locations in the cochlea. At 400 ppm, 25% OHC loss was found at the 11- and 21-kHz region. The highest concentration evoked 40% and 75% OHC loss at the 11- and 21-kHz location, respectively. Thus, the mid-frequency region of rats is affected after exposure to relatively low concentrations of ethyl benzene (400-550 ppm). These results indicate that ethyl benzene is one of the most potent ototoxic organic solvents known today.

The ototoxic effects of ethyl benzene in rats

Exposure to organic solvents has been shown to be ototoxic in animals and there is evidence that these solvents can induce hearing loss in humans. In this study, the effects of inhalation of the possibly ototoxic solvent ethyl benzene on the cochlear function and morphology were evaluated using three complementary techniques: (1) reflex modification audiometry (RMA), (2) electrocochleography and (3) histological examination of the cochleas. Rats were exposed to either ethyl benzene (800 ppm, 8 h/day for 5 days) or to control conditions. The RMA threshold increased significantly by about 25 dB, 1 and 4 weeks after the exposure, irrespective of the stimulus frequency tested (4-24 kHz). Electrocochleography was performed between 8 and 11 weeks after exposure to the organic solvent. The threshold for the compound action potential increased significantly by 10-30 dB at all frequencies tested (1-24 kHz). Histological examination of the cochlea showed outer hair cell (OHC) loss, especially in the upper basal and lower middle turns (corresponding to the mid-frequency region) to an extent of 65%. We conclude that exposure to 800 ppm ethyl benzene for 8 h/day during 5 days induces hearing loss in rats due to OHC loss.

Simultaneous exposure to ethyl benzene and noise : Synergistic effects on outer hair cells

The effects on hearing of simultaneous exposure to the ototoxic organic solvent ethyl benzene and broad-band noise were evaluated in rats. The effects of three ethyl benzene concentrations (0, 300 or 400 ppm) and three noise levels (95 or 105 dB(lin) SPL or background noise at 65 dB(lin) SPL) and all their combinations were investigated for a 5 day exposure at 8 h/day. Distortion product otoacoustic emissions and compound action potentials were affected after 105 dB noise alone, and after 105 dB noise in combination with ethyl benzene (300 and 400 ppm). However, the amount of loss for these combinations did not exceed the loss for 105 dB noise alone. Outer hair cell (OHC) loss after exposure to 300 ppm ethyl benzene was located in the third row of OHCs. At 400 ppm, the loss spread out to the second and first row of OHCs. Noise alone hardly affected the OHC counts except for a minor loss in the first row of OHCs after 105 dB SPL. Noise at 105 dB in combination with ethyl benzene at 300 and 400 ppm, however, showed OHC loss greater than the sum of the losses induced by noise and ethyl benzene alone.

Comparative hazard identification of nano- and micro-sized cerium oxide particles based on 28-day inhalation studies in rats

Abstract There are many uncertainties regarding the hazard of nanosized particles compared to the bulk material of the parent chemical. Here, the authors assess the comparative hazard of two nanoscale (NM-211 and NM-212) and one microscale (NM-213) cerium oxide materials in 28-day inhalation toxicity studies in rats (according to Organisation for Economic Co-operation and Development technical guidelines). All three materials gave rise to a dose-dependent pulmonary inflammation and lung cell damage but without gross pathological changes immediately after exposure. Following NM-211 and NM-212 exposure, epithelial cell injury was observed in the recovery groups. There was no evidence of systemic inflammation or other haematological changes following exposure of any of the three particle types. The comparative hazard was quantified by application of the benchmark concentration approach. The relative toxicity was explored in terms of three exposure metrics. When exposure levels were expressed as mass concentration, nanosized NM-211 was the most potent material, whereas when expression levels were based on surface area concentration, micro-sized NM-213 material induced the greatest extent of pulmonary inflammation/damage. Particles were equipotent based on particle number concentrations. In conclusion, similar pulmonary toxicity profiles including inflammation are observed for all three materials with little quantitative differences. Systemic effects were virtually absent. There is little evidence for a dominant predicting exposure metric for the observed effects.

Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene

The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was found in the corresponding cochlear regions. In contrast, guinea pigs showed no threshold shifts and no OHC loss after exposure to much higher ethyl benzene levels (2500 ppm, 6 h/day, 5 days). Subsequently, a limited study (four rats and four guinea pigs) was performed in an attempt to understand these differences in susceptibility. Ethyl benzene concentration in blood was determined in both species after exposure to 500-ppm ethyl benzene (8 h/day, 3 days). At the end of the first day, blood of the rats contained 23.2+/-0.8-microg/ml ethyl benzene, whereas the concentration in guinea pig blood was 2.8+/-0.1 microg/ml. After 3 days, the concentration in both species decreased with respect to the first day, but the ethyl benzene concentration in rat blood was still 4.3 times higher than that in guinea pig blood. Thus, the difference in susceptibility between the species may be related to the ethyl benzene concentration in blood.

Vibration sensitivity as a parameter for detecting peripheral neuropathy. I. Results in healthy workers.

SummaryTwo methods of evaluating the threshold for vibration perception were compared. Surprisingly it appears that the theoretically attractive, adaptive forced choice method does not result in lower variability than the method of limits. Moreover two devices were used to evaluate the threshold: the Optacon Tactile Tester and the “multirod”. Based on the characteristics of these devices and the known properties of mechanoreceptors, it is argued that the two devices test different mechanoreceptor systems. The high correlation of threshold with age (r = 0.9) found by Arezzo and Schaumburg [1] in measurements with the Optacon could not be reproduced.

Behavioral effects of exposure to organic solvents in carpet layers

Carpet layers and age-matched controls were investigated both at the beginning of a working day and at the end with four subtests of a neuropsychological test battery (NES2). Exposure to toluene, cyclohexane, ethyl acetate, and heptane was measured with personal air sampling methods. One group of carpet layers used water-based adhesives (WBA) on the day the investigation took place and the other group used contact adhesives (CA) on that day. The WBA group was exposed primarily to toluene, and the CA group was exposed to other solvents as well. Initial (before work) differences in neuropsychological scores between all exposed workers and controls could be attributed to differences in education, the carpet layers being somewhat higher educated. No differences were found between the solvent-exposed and control groups that would suggest persistent effects of chronic solvent exposures. The improvement in test scores over the day was the same in both groups. However, evidence for exposure-related changes in test scores over the day were found within the exposed group.