Solvent-induced chronic toxic encephalopathy

Chlorinated solvents, especially trichloroethylene, have been extensively used for metal degreasing since the beginning of this century. There have been case reports of cranial nerve damage and symptoms of acute and reversible encephalopathy. However, another issue during the last decade is the possible existence of a syndrome of chronic cerebral dysfunction. Our study deals with the risk of developing a state of psychoorganic syndrome after long-term exposure to solvents, mainly trichloroethylene. In this historical cohort study, 96 metal degreasers participated in a clinical medical and psychological examination. The risk of developing psychoorganic syndrome was proportional to the exposure duration, to increasing age, and to decreasing primary intellectual level. Using logistic regression analysis, there was a significantly increased risk of developing psychoorganic syndrome from solvent exposure. There was an odds ratio of 5.6 (0.93–34.3) for psychoorganic syndrome in the medium-exposed group. In the most highly exposed group, with a mean full-time exposure duration of 11 years, there was a significantly increased risk of psychoorganic syndrome, the adjusted odds ratio was 11.2 (1.9–66.6). None of four other potential confounders (arteriosclerotic disease, neurologic/psychiatric disease, alcohol abuse, and current solvent exposure) had any significant associations to psychoorganic syndrome. © 1993 Wiley-List, Inc.     

Mixed solvent exposure and cerebral symptoms among active and retired workers. An epidemiological investigation of 3387 men aged 53–75 years

In an epidemiological study comprising 3,387 men aged 53 to 75 years, 3303 men with valid questionnaire answers to questions on occupational organic solvents exposure, four cerebral symptoms and current work status were examined. Two-hundred and ninety-five men had been occupationally exposed to mixed organic solvents for a period of 5 years or more. Among them 178 were retired, while 117 were still gainfully employed. The exposed men in both groups had highly significantly more complaints of decreased concentration ability and of memory difficulties. Of the exposed retired men a higher prevalence of headache was found. Among the exposed still employed a trend towards a higher prevalence of dizziness was found. This study was conducted within a cardiovascular study with no focus on the relationship between organic solvent exposure and cerebral symptoms, a design reducing the risk of overreporting. If overreporting was responsible for the differences found between solvent-exposed and unexposed cases a similar pattern for reporting of acute and chronic symptoms should be expected. This was not the case. Our results support the hypothesis, that occupational exposure to organic solvents for a period of 5 years or more increases the risk of developing persistent memory difficulties and a decrease in concentration ability.     

An effective organic solvent system for the dissolution of amino acids

Dimethylformamide containing strong acids (CF₃ COOH, HBF₄. TosOH, etc.) and an excess of tertiary base with p^K≤6 is an effective solvent system for the dissolution of amino acids and their derivatives. The preferable base is pyridine, which forms a system with an apparent pH of 5.3. Amino acids dissolved in this solvent system readily interact with acylating reagents (BOC₂O, ZOSu, Fmoc-OSu and activated derivatives of N-protected amino acids). A number of BOC-, Z-, Fmoc-amino acids, as well as several dipeptides, were synthesized using this solvent system with 80-99%) yields. © Munksgaard 1996.     

Do organic solvents induce changes in the dopaminergic system? Positron emission tomography studies of occupationally exposed subjects

Objectives: The objective of this study was to test the hypothesis that long-term occupational exposure to organic solvents may effect the levels and turnover of dopamine in man. Methods: A study was performed on 17 patients with neuropsychiatric symptoms due to occupational solvent exposure, and 11 healthy non-exposed male volunteers (controls). Positron emission tomography (PET) was used to assess striatal dopaminergic function, using l-[¹¹C]DOPA, [¹¹C]nomifensine and [¹¹C]raclopride as tracers. Results: The rate of dopamine synthesis was significantly increased among subjects with occupational exposure to organic solvents compared with non-exposed controls. After controlling for the difference in age between exposed and controls, the effect of solvent exposure became less apparent and was reduced from +32% (P = 0.009) to +25% (P = 0.07). There were no differences with regard to the binding of [¹¹C]nomifensine. Patients with and without the diagnosis of toxic encephalopathy did not differ with regard to their putaminal uptake of l-[¹¹C]DOPA, [¹¹C]nomifensine and [¹¹C]raclopride. Conclusion: The data support the hypothesis that long-term exposure to organic solvents may increase the rate of dopamine synthesis in the brain without affecting the number of presynaptic terminals or postsynaptic dopamine receptors. Received: 8 October 1996 / Accepted: 7 February 1997     

Prognosis of symptoms in patients with diagnosed chronic organic solvent Intoxication

Summary The profile and prognosis of symptoms of 87 patients (mean age 38.6 years) in whom a chronic organic solvent intoxication due to tri- or perchloroethylene or mixtures of solvents had been diagnosed 3–9 years earlier were examined by means of an interview.Both at the time of diagnosis and upon reexamination, the most common symptoms were abnormal fatigue, memory disturbances and headache. Also dizziness, sleep disturbances, sensory symptoms in the extremities, mental depression, concentration difficulties, psychic irritability, emotional lability, tremor and nausea were present in over 60% of patients at the time of diagnosis. Upon reexamination, 52% of the intoxication patients with no other contributing neurological disease felt that their overall subjective condition was better than at the time of diagnosis, 21% felt that it was worse, and 27% reported no change. Most of the individual symptoms had more often changed for the better than for the worse; the differences were statistically significant with regard to abnormal fatigue, headache, dizziness, sleep disturbances, nausea, and emotional lability, whereas memory disturbances had changed in the opposite direction. Younger persons, who had had a longer follow-up period and without regular check-ups at the Institute of Occupational Health seemed to have better prognosis at the group level. Due to the great variation between the individuals, the prognosis was, however, impossible to predict in individual cases.     

Behavioral and neurochemical alterations in the offspring of rats after maternal or paternal inhalation exposure to the industrial solvent 2-methoxyethanol

The industrial solvent 2-methoxyethanol (2ME) has antifertility effects in male rats at 300 ppm and is tetragenic in rats and rabbits at 50 ppm. The present research investigated if exposure of paternal or maternal animals to 25 ppm 2ME, the current U. S. permissible occupational exposure limit, would produce detectable effects in the offspring. Eighteen male young-adult Sprague-Dawley rats were exposed to 25 ppm 2ME 7 hr/day, 7 days/week for 6 weeks; they were then mated with untreated females which were allowed to deliver and rear their young. In addition, groups of 15 pregnant rats were exposed 7 hr/day on gestation days 7–13 or 14–20 and allowed to deliver and rear their young. At birth, litters were culled to 4 females and 4 males for behavioral testing of neuromotor function, activity, and simple learning ability on days 10 through 90. In addition, brains from new born and 21-day-old offspring were analyzed for neurochemical deviations from controls. No effects on paternal or maternal animals, nor on the number or weight of live offspring, were noted. Behavioral testing revealed significant differences from controls only in avoidance conditioning of offspring of mothers exposed on days 7–13. In contrast, neurochemical deviations were observed in brains from 21-day-old offspring from the paternally exposed group as well as from both maternally exposed groups; changes were numerous in the brainstem and cerebrum but were fewer in the cerebellum and midbrain. Thus it appears that both paternal and maternal inhalation of 25 ppm 2ME produces some effect which is reflected in neurochemical deviations in the offspring.     

氨苄青霉素钠中有机溶媒残留量的测定与考察

本文用气相色谱法考察测定了全国７个生产厂家２２个批号的氨苄青霉素钠有机溶媒残留量，色谱条件为１０％的聚乙二醇（ＰＥＧ）－１００００和３．５％－缩二甘油（ＤＧ）混合玻璃色谱柱，柱温６５℃，ＦＩＤ检测器，以正内醇为内标，测定结果，残留溶媒及残留量主要有异丙醇０．０１９％～０．４１０％，二氯甲烷０．０２５％～０．０５１％，丙酮０．００３％～０．００６％。     

Vasoactive intestinal polypeptide (VIP) in cerebrospinal fluid from men after long-term exposure to organic solvents

Vasoactive intestinal polypeptide (VIP) is widely distributed within the central nervous system (CNS) and is thought to function as a neurotransmitter. VIP was measured in CSF from 14 men with psycho-organic syndrome occupationally exposed to organic solvents for 7-38 years and in CSF from 8 neurologically healthy male volunteers. The concentration of VIP in the exposed group, 28 +/- 15 (SD) pmol/l, did not significantly differ from that of controls, 38 +/- 14 pmol/l. Thus, determination of VIP in CSF appears to be of little value for detecting effects of long-term solvent exposure.