Biochemical, neuropsychological, and neurological abnormalities following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.

Presented herein are the results of follow-up examinations of 13 workers performed in 1996--30 yr following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication in a herbicide production plant. In these workers, the current mean plasma level of 2,3,7,8-TCDD, measured by high-resolution gas chromatography/high-resolution mass spectrometry, was 256 pg/gm lipid (range = 14-760 pg/gm lipid). This mean value corresponded to an estimated concentration of approximately 5,000 pg/gm plasma fat that existed about 30 years ago. Such a mean plasma level indicates that this group was one of the most heavily exposed groups to 2,3,7,8-TCDD described in the literature. Patients with persistent chloracne had significantly higher plasma levels of 2,3,7,8-TCDD than persons without chloracne. A significant, positive correlation was found between plasma levels of 2,3,7,8-TCDD in 1996 and levels of cholesterol and plasma lipids that existed since 1974. During 1996, there was a significant positive correlation between 2,3,7,8-TCDD and levels of beta-lipoproteins, cholesterol, and triglycerides. Also in 1996, significant correlations were found between neuropsychological variables and plasma levels of 2,3,7,8-TCDD. Other significant correlations were observed between neuropsychological variables and (1) the highest levels of triglycerides (i.e., since the year 1989), (2) levels of triglycerides in 1996, (3) levels of cholesterol at the first examination (i.e., 1969-1970), (4) highest level of cholesterol since the year 1969, and (5) cholesterol levels in 1996. Such correlations are biologically plausible, and they provide evidence of impaired cognitive performance (i.e., memory first), with a concurrent increase of plasma lipid levels. Abnormal electromyography, electroencephalography, and visual evoked potentials were observed in 23%, 54%, and 31 %, respectively, of former workers. Abnormal electroencephalography findings occurred more frequently in workers who had 2,3,7,8-TCDD blood levels that exceeded 200 pg/gm plasma fat than in workers with 2,3,7,8-TCDD values lower than 200 pg/gm plasma fat (p < .025). Frequency of polyneuropathic EMG abnormalities decreased from 38% in the 1970s to 23% in 1996. Improvement of conduction velocity in the tibial nerve was statistically significant (p < .05).

Oxidative phenotype polymorphism (P450 2D6) and metabolism of toluene.

Oxidative phenotype P-450 2D6 was examined using sparteine test in 3 groups of persons to determine if there is a coincidence in the defect of the oxidative biotransformation of sparteine and impaired oxidation of toluene, which could explain interindividual differences in the amounts of hippuric acid in the urine in exposed persons. The following groups of persons were examined: 30 rotogravure printers exposed to toluene vapors at concentrations of 8-307 ppm; 20 workers, 2 months after the cessation of the long-term exposure to toluene at concentrations of 104-1,170 ppm; 48 healthy volunteers with no exposure to toluene. Among the 98 persons 5 poor metabolizers (PMs) of sparteine were found, none in the group of printers exposed to toluene. In the experimental exposure chamber 5 PMs and 6 extensive metabolizers (EMs) were exposed to toluene concentration of 245 ppm for 5 hours. Hippuric acid and o-cresol in the urine, and toluene both in blood and in alveolar air were measured. However, no significant differences were found in either of these parameters between the PM and EM groups. Thus, the sparteine test does not appear to be applicable in the identification of persons with higher risk arising from toluene exposure.

Long-term follow-up after accidental gamma irradiation from a 60Co source.

In December 1973 a technician was accidentally irradiated when attempting to bring under control a sealed 60Co source (110 TBq) which had been lodged in the head of a medical irradiation unit during a replacement operation. In the early period after the accident, severe skin changes on the left hand, epilation in a small area of the left temporal region and minor deviations in peripheral blood developed. In the following years, repeated surgery due to secondary skin defects of the left hand resulted in the loss of the fingers 2-5. Since 1975, changes in the lens of the left eye began to appear leading gradually to the deterioration of visual acuity. Later, opacities of the lens of the right eye were found. The patient's psychological and emotional attitude about the accident changed in the course of time. The factors influencing the psychic state of the patient are identified.

The development and prognosis of chronic intoxication by tetrachlordibenzo-p-dioxin in men.

During 1965 to 1968, 80 workers who had been engaged in the production of 2, 4, 5-sodium trichlorphenoxyacetate and butylester of trichlorphenoxyacetate acid became ill. The cause of the illness was 2, 4, 7, 8-tetrachlordibenzo-p-dioxin. A 10-yr study has been conducted for 55 exposed individuals. The majority of the patients developed chloracne, and 11 manifested porphyria cutanea tarda. Approximately one-half of the patients suffered from metabolic disturbances, i.e., pathologically elevated lipids with abnormalities in the lipoprotein spectrum, and two-fifths of the patients had pathological changes in the glucose tolerance test. One-third of the patients had biochemical deviations indicative of a mild liver lesion. Histological examination revealed light steatosis, or periportal fibrosis, or activation of Kupffer cells. Fluorescence of the liver tissues was present in ultraviolet light. In 17 persons symptoms of nervous system focal damage existed, with predominance of peripheral neuron lesion of the lower extremities (verified by EMG examination). The majority of patients suffered from various psychological disorders. As of this date, two patients have died of bronchogenic lung carcinoma; one of liver cirrhosis; one of a rapidly developed, extremely unusual type of atherosclerosis precipue cerebri; and two patients have died in traffic accidents. The conditions of most other patients have improved.

Changes in the blood count of growing rats irradiated with a microwave pulse field.

A group of 20 male rats of mean initial body weight of 65.53 g were irradiated for 7 wk (5 days per wk, 4 hr per day) with an electromagnetic pulse field of the following parameters: working frequency 2,736.5 MHz; repeated frequency 395 Hz; pulse width 2.6 musec; vertical polarization; mean power density 24.4 mW/cm2; accuracy of measuring +/- 6%. The rectal temperature of experimental animals increased during irradiation by a maximum of 0.5 degrees C. Blood was taken before irradiation, at the end of the 1st, 3rd, 5th, and 7th wk of irradiation, and at the end of the 1st, 2nd, 6th, and 10th wk after irradiation was completed. The parameters under study included the hematocrit value; number of leukocyte differential count in both absolute and relative proportions; activity of alkaline phosphatase in neutrophil leukocytes; and body weight increase. The results were compared with parallel data obtained from a control group of 20 animals and evaluated by Student's t test at a significance level of 1%. In the second half of the irradiation period the experimental animals exhibited significantly lower mean hematocrit values, lower numbers of leukocytes, and lower absolute numbers of lymphocytes. These changes disappeared gradually within 10 wk after completed irradiation. Activity of alkaline phosphatase in neutrophil leukocytes was significantly increased in the 1st wk of irradiation and dropped transiently after the irradiation. In the post-irradiation interval experimental animals displayed significant decline in rate of body weight increase. The level of the other examined parameters did not differ from the controls.