n-Hexane intoxication in a Chinese medicine pharmaceutical plant: a case report.

BACKGROUND: n-Hexane is a well-known neurotoxicant. Polyneuropathy due to occupational n-hexane exposure has been reported worldwide, however, our case is the first report in the Chinese herb industry. CASE PRESENTATION: A 25-year-old Asian man experienced progressive weakness and numbness in his hands and feet after working as an operator in a Chinese medicine pharmaceutical plant for the manufacture of Chinese herbal pain relief patches for 10 months. Electrophysiological studies indicated a reduction in nerve conduction velocity, prolongation of distal latencies, mildly positive sharp waves, and reduced recruitment with polyphasic potentials, particularly at distal sites. Demyelination with axonal degeneration caused by occupational n-hexane exposure was strongly suspected. Through investigation of our patient's workplace, the ambient n-hexane concentration in air was found to considerably exceed the permissible exposure limit/time-weighted average for n-hexane in Taiwan. His symptoms were gradually relieved after 4 months of cessation of exposure to n-hexane. He was then confirmed as a case of occupational n-hexane intoxication. Further effective control measures should be implemented as soon as possible to prevent exposure of workers to n-hexane. CONCLUSIONS: Despite a typical clinical presentation, his exposure at workplace was appropriately investigated. Chemical exposure in Chinese medicine pharmaceutical plants could be an emerging issue that may affect workers' health. The lack of knowledge and management of solvents could endanger the health of workers. This case has profound educational implications for occupational health and is worthy of further follow-up for improving hazards control.

Solvent exposure and cognitive function in automotive technicians.

Automotive technicians are commonly exposed to organic and chlorinated solvents, particularly through use of cleaning products. Occupational solvent exposures have been associated with deficits in cognitive function but, to our knowledge, no previous studies have investigated automotive technicians. The purpose of the present study was to investigate whether previous exposures to n-hexane, in particular, or general solvents posed a persistent neurotoxic hazard to automotive workers. Enrolled in the study were 830 San Francisco Bay Area automotive repair workers. Each participant underwent a battery of cognitive function tests to investigate central nervous system impairment, with a primary focus on the domains of psychomotor speed, fine motor function, memory and mood. Cognitive test results regressed against estimated hexane and total solvent exposures showed little evidence of associations. Exposures to both solvents and hexane were well below the occupational exposure limits. Our results provide some reassurance about persistent neuropsychological effects in automotive workers who use solvent-based products and those who previously used hexane-containing automotive cleaning products, since this solvent is believed no longer to be used in automotive cleaning products. The lack of observed effect in this study may be attributable to low exposures, or it may reflect improved cognitive function since hexane use in automotive cleaning products was discontinued. However, impacts on results of exposure misclassification and/or the healthy worker survivor effect cannot be discounted. Irrespective of the outcome of this study, the main known neurologic effect of n-hexane is peripheral neuropathy, and such an association in automotive technicians is not excluded by these results.

[Determination of normal reference value of pyrrole adducts in urine in young people in a university in Shandong, China].

OBJECTIVE: To determine the normal reference value of pyrrole adducts in urine in young people in a university in Shandong, China, and to provide a reliable basis for the clinical diagnosis of n-hexane poisoning. METHODS: A total of 240 college students were randomly selected. After excluding 32 ineligible students, 208 subjects were included in this study, consisting of 104 males and 104 females, with a mean age of 21?3 years (range: 18 to 24 years). Morning urine was collected from each subject. The content of pyrrole adducts was determined by chromatometry. RESULTS: The content of pyrrole adducts in both male and female obeyed a positively skewed distribution. The median level of pyrrole adducts in male subjects was 0.88 nmol/ml, and the reference value was 0.14-3.92 nmol/ml. The median level of pyrrole adducts in female subjects was 0.93 nmol/ ml, and the reference value was 0.09-3.27 nmol/ml. Student's t test identified no statistical difference in pyrrole adduct level between male and female subjects (t=0.15, P>0.05). CONCLUSION: The median level of pyrrole adducts in normal young people is 0.91 nmol/ml, and the reference value is 0.11-3.95 nmol/ml.

[Analysis of occupational chronic n-hexane poisoning economic burden].

OBJECTIVE: To study the economic burden caused by occupational chronic n-hexane poisoning. METHODS: Information about the cost of treatment, compensation, board, wage, diagnosis, escorts, transportation and the days off work were collected in a 34 cases of occupational chronic n-hexane poisoning accident to estimate the economic burden. RESULTS: There were 4 mild, 19 moderate, 11 severe in the 34 cases and the total cost was 6 084 809 yuan. The hospitalization days was respectively (204.0 ± 3.7) d, (226.6 ± 78.3) d and (417.6 ± 94.1) d, averaging (285.8 ± 96.3) d. The treatment cost was respectively 62 525.8, 69 409.7 and 128 155.6 yuan. The compensation was respectively 20 000.0, 20 052.6 and 30 290.9 yuan. The wage was respectively 23 460.0, 26 062.6 and 47 644.0 yuan. The board was respectively 17 566.5, 19 499.8 and 36 230.1 yuan. The days of work was respectively (176.8 ± 3.2) d, (196.4 ± 67.9) d and (361.4 ± 81.6) d, averaging (247.7 ± 83.5). The lost productivity was respectively 1 809 724.8, 2 010 350.4 and 3 699 290.4 yuan. CONCLUSION: The economic burden of occupational chronic n-hexane poisoning was so heavy that prevention measures should be strengthened.

Electrophysiological follow-up of patients with chronic peripheral neuropathy induced by occupational intoxication with n-hexane.

The aim of this study is to characterize and dynamically monitor the progress of peripheral neuropathy induced by n-hexane by electromyography and nerve conduction velocity (NCV-EMG). Twenty-five patients with n-hexane poisoning from an electronic company were investigated in the year 2009. The occupational history of these workers was collected, and toxic substance exposure was identified. Neurologic inspection and regular NCV-EMG inspection were performed for all patients upon hospital admission and after 3, 6, and 12 months of treatment. NCV-EMG results shown that patients with n-hexane poisoning have simultaneous damage on motor and sensory nerves, of which sensory nerve damage was more severe. Motor nerves of the lower limbs were severe damaged than those of the upper limbs; whereas injury of sensory nerve in the upper limbs was more severe than that of the lower limbs. After treatment, clinical signs and symptoms of the patients were significantly improved. NCV-EMG result showed a delayed worsening at 3 months then gradually recovered after 12 months. Recovery of the motor nerve was better compared with sensory nerve, with upper limbs faster than that of the lower limbs.

[Misdiagnosis of occupational chronic n-hexane poisoning: an analysis of 16 cases].

OBJECTIVE: To analyze the cause of misdiagnosis of occupational chronic n-hexane poisoning and to investigate the diagnosis and differential diagnosis of this disease. METHODS: The clinical data of 16 patients with occupational chronic n-hexane poisoning who had been misdiagnosed with other diseases were collected. The hospital they first visited, cause of misdiagnosis, clinical features, and the misdiagnosis rate among inpatients during the same period were retrospectively analyzed. RESULTS: Sixteen of 62 patients hospitalized during the same period were misdiagnosed at the first visit; 11 cases were in the upper first-class hospitals, and 5 cases in the upper second-class hospitals; 5 cases were misdiagnosed as Green Barry syndrome, 2 cases as motor neuron disease, 2 cases as drug-induced peripheral neuropathy, 3 cases as periodic paralysis, and 4 cases had uncertain diagnosis. CONCLUSION: Most doctors who work in ordinary hospitals do not know occupational chronic n-hexane poisoning, which is often misdiagnosed as general neuropathies or difficult diseases. The key to correct diagnosis is to know the patient's occupational history and clinical features.

[Effect of 2,5-hexanedione on light-molecular-weight neurofilaments (NF-L) degradation of rat nerve tissues].

OBJECTIVE: To investigate the effect of 2,5-hexanedione (HD) on degradation of low-molecular-weight neurofilaments (NF-L) in nervous tissue of rats, and to explore the molecular mechanism of n-hexane neuropathy. METHODS: Fifty male Wistar rats were randomly divided into one-week poisoning group (n = 10), two-week poisoning group (n = 10), three-week poisoning group (n = 10), four-week poisoning group (n = 10), and control group (n = 10). In the four poisoning groups, a rat model of n-hexane neuropathy was established by intraperitoneal injection of HD (400 mg/kg/d). The change in the sciatic nerve ultrastructure of each rat was observed under an electron microscope. The progression of HD-induced peripheral neuropathy was evaluated using a gait scoring system. The degradation rates of NF-L in the sciatic nerve and spinal cord of each rat were measured by Western Blotting. RESULTS: The rats showed decrease in muscle strength and abnormal gait after two weeks of HD poisoning and mild or moderate paralysis after four weeks of HD poisoning. The sciatic nerve showed degenerative change, according to electron microscope observation. Compared with the control group, the two-week poisoning group, three-week poisoning group, and four-week poisoning group had the NF-L degradation rates decreased by 25.8%, 70.4%, and 69.7%, respectively, in the supernatant fraction of sciatic nerve, and by 14.7%, 64.6%, and 67.3%, respectively, in the sediment fraction of sciatic nerve, all showing a significant difference (P < 0.01). Compared with the control group, the one-week poisoning group had the NF-L degradation rate decreased by 33.87% in the supernatant fraction of spinal cord, the four-week poisoning group had the NF-L degradation rate increased by 16.2% in the supernatant fraction of spinal cord, and the one-week poisoning group and two-week poisoning group had the NF-L degradation rates decreased by 46.3% and 13.0% in the sediment fraction of spinal cord, all showing a significant difference (P < 0.01). CONCLUSION: HD poisoning significantly inhibits NF-L degradation in the sciatic nerve, which may be associated with NF degeneration and accumulation in the axons of patients with n-hexane neuropathy.

[Pathology and neurophysiology analysis for peripheral neuropathy of four patients with chemicals poisoning].

OBJECTIVE: To study the nerve electromyogram results by analysing the pathological characters of 4 cases diagnosed as peripheral neuropathy caused by n-hexane and arsenic. METHODS: The nerve electromyogram examination and pathology data of 4 patients, who had been diagnosed as toxic chemicals peripheral neuropathy, were studied retrospectively. RESULTS: Two patients in this group were exposed to n-hexane, their nerve electromyogram examinations and biopsy pathology of superficial peroneal nerve indicated the peripheral neuropathy was mainly manifests the lesion of medullary sheath. Another two patients were exposed to arsenic, their nerve electromyogram examinations showed axonal degeneration associated with demyelination, and their biopsy pathology showed the peripheral neuropathy was mainly axonal degeneration. CONCLUSION: Axonal degeneration and demyelination always coexist in peripheral neuropathy caused by chemicals.

[A study of sympathetic skin response to the damage of autonomic nerves function in patients with chronic N-hexane poisoning].

OBJECTIVE: To study the sympathetic skin response (SSR) to the effects of N-hexane on autonomic nerves function in patients with chronic N-hexane poisoning. METHODS: The subjects in present study included 30 controls and 37 cases with chronic N-hexane poisoning. Also 37 patients were divided into 3 subgroups (mild, moderate and severe poisoning) according to diagnostic criteria of occupational diseases. All subjects were examined by SSR test and nerve conduction velocity (NCV) test. All patients were reexamined by SSR and NCV every 1 ∼ 2 months. The differences in SSR parameters (latency, amplitude) among groups were observed. In the severe poisoning subgroup, the changes of SSR and NCV parameters (conduction velocity, amplitude) in different poisoning stages were observed. RESULTS: There were significant differences in SSR latency of upper extremity among groups and the significant differences in SSR amplitude of upper and lower extremity among groups (P < 0.05). No significant differences in SSR parameters were found between the adjacent groups (P > 0.05). There were significant differences in SSR latency of upper extremity during different periods and the significant differences in SSR amplitude of upper and lower extremity during different periods among all groups (P < 0.05). The change of SSR parameters consistent with that in NCV. The longest SSR latency of upper extremity and the smallest SSR amplitudes of upper and lower extremity appears 1 - 2 months earlier than that of the smallest action potential amplitude. CONCLUSION: The damage of autonomic nerves induced by N-hexane increased with poisoning progresses. The damage of autonomic nerves corresponded with the damage of myelin sheath of large myelinated nerves, but which appeared 1 - 2 months earlier than the damage of axon of large myelinated nerves. SSR test may serve as a method to detect the damage of autonomic nerves function in patients with chronic N-hexane poisoning.

Exposición a solventes y disfunción auditiva central: revisión de la evidencia científica / Solvent exposure and central auditory dysfunction: a literature review on the scientific evidence

Diversos estudios han demostrado que los solventes orgánicos pueden inducir una disfunción auditiva. Los modelos animales han mostrado que los solventes son capaces de dañar las células ciliadas externas. Estudios de campo en trabajadores expuestos a solventes han encontrado por una parte, una mayor prevalencia de hipoacusia sensorioneural en comparación a grupos controles, y por otra, una dis función auditiva central asociada a la exposición a solventes. El presente trabajo tiene como objetivo revisar y discutir la evidencia científica acerca de la disfunción auditiva central asociada a la exposición a solventes como el tolueno, estireno, xileno, bisulfato de carbono, y mezcla de ellos. Se discuten los resultados de las investigaciones llevadas a cabo en humanos expuestos laboralmente a estos agentes. Se discuten además, los mecanismos de ototoxicidady neurotoxidad de los solventes y sus implicancias en la evaluación de la hipoacusia inducida por solventes.

Different studies have demonstrated that solvents may induce an auditory dysfunction. Animal models have shown that solvents can injure the outer hair cells. Studies conducted in workers exposed to solvents have found on one hand, a higher prevalence of sensorineural hearing loss in comparison to non-exposed control group subjects. On the other hand, these studies have found a central auditory dysfunction associated with solvent exposure. The present manuscript aims at revising and discussing the scientific evidence on central auditory dysfunction associated with exposure to solvents such as toluene, styrene, xylene, carbon disulphate, and mixtures. Results from studies conducted in humans occupationally exposed to solvents are discussed. Also, the oto-and neuro-toxicity induced by solvents and the implications for the assessment of solvent-induced hearing loss are addressed.