Effects of dioxins and furans on liver enzymes, lipid parameters, and thyroid hormones in former thermal metal recycling workers.

A cross-sectional study was performed to examine the internal exposure of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDF) in former workers in a nonferrous metal recycling facility. Liver enzymes, lipid parameters, and thyroid hormones were measured to check possible biologic effects. Compared to background levels, the international toxicity equivalent levels of exposed workers were slightly elevated (median 42 ppt, range 13-281 ppt). The workers also had higher total PCDF concentrations (median 128 ppt, range 30-1138 ppt). Correlation analyses demonstrate significant associations with only one liver enzyme, alanine aminotransferase. There were no such associations with serum cholesterol levels or with serum thyroid hormones. Because of the cross-sectional design of the study, firm conclusions cannot be drawn. For further evaluation, a follow-up examination appears necessary.


Introduction and Aim of the Study
In 1985 high concentrations of dioxins and furans in soil and dust were found close to a nonferrous metal recycling plant located in Rastatt, a small town in southwestern Germany (1,2). Recovery of copper was the main objective of the recycling plant. Dust generated during thermal metal recycling processes of scrap material such as cables and electronic equipment and other equipment was identified as the main source of polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF).
Because no data were available on the extent of PCDD/PCDF exposure of former workers-the plant closed in 1986the legal accident insurance organization (Edel-und Unedelmetall-Berufsgenossenschaft, Stuttgart, Germany) decided to offer all employees a comprehensive medical examination. A steering group was established to coordinate and organize the activities, and especially to identify and recruit the subjects under study.
representative sample of the workforce. Second, health status of each worker was determined in comprehensive medical examinations carried out between 1992 and 1995. Details of the study group and methods are described elsewhere (3). In light of the well-known or suspected adverse effects of PCDD/PCDF exposure, liver function, lipid metabolism, and thyroid function were chosen target organs and the mechanisms to be investigated (4,5).

Materials and Methods
The workforce studied consisted of a total of 675 persons employed between 1961 to 1986 ( Table 1). Duration of employment ranged from a few months up to almost 40 years. Despite intensive efforts only 250 persons could be completely examined. The main reasons for nonparticipation in the study were lack of interest (167 workers), emigration abroad, and unknown residence (194 workers).
PCDD/PCDF blood analyses were carried out on 76 subjects (70 men and 6 women). Relevant variables such as age, duration of employment, and time between end of employment and examination were not significantly different among the subgroups and the whole cohort ( Table  2). A comparison of work functions was not possible because of lack of data.  Workcers in othe areas Low evaluation of PCDD/PCDF concentrations in dust samples, the production process, and geographic and meteorologic aspects of the process. The relatively high exposures in office workers was explained by the fact that the predominant wind direction appears to have led to increased dust pollution in this area of the plant. PCDD and PCDF levels were analyzed in worker blood samples by gas chromatography/mass spectrometry after separation of the blood lipids. The analytical procedure is described in detail elsewhere (6).
To examine the target organs or functions, the following parameters were determined: y-glutamyltranspeptidase   (7) were chosen; these results were calculated from analyses of 102 nonoccupationally exposed individuals from Germany. Because all blood samples were measured in the same laboratory using identical methods, systematic analytical errors were unlikely. to those of the normal population. The highest concentration was 1138 ppt, about 6-fold above the maximum background level. It must be mentioned, however, that the average age of control subjects is about 10 years below that of the study group (median 39 [22-69] years of age). Because of age dependent increases in body burden of PCDD/PCDF, the differences are more pronounced (8).
Further analyses showed that penta-, hexa-, and hepta-chlorodibenzofurans (CDF) contributed most to the elevated internal exposure (Figure 1). This pattern is partly in accordance with the distribution of PCDD/PCDF in dust samples (2). It can be used as an indicator of PCDD/ PCDF exposure during nonferrous metal recycling procresses.
With respect to the biochemical parameters and the fact that an adequate control group was not examined, the subjects were dichotomized into low-and high-exposure subgroups ( Table 5). Low exposure was defined as having an international toxicity equivalent (I-TEQ) below 38 ppt, the median of the background level in nonoccupationally exposed persons (7). Highly exposed workers had increased total PCDF concentrations caused by the congeners penta-, hexa-, and octafurans. Results of examination of the biochemical parameters of both highand low-exposed workers are given in Table 6. The only significant difference found was an increased serum cholesterol level in high exposure subgroup. Triglyceride serum levels were also measured. They were not further analyzed, however, because not all workers fasted before their blood samples were collected.
To evaluate possible relationships between internal exposure and biochemical parameters, correlation analyses were performed (Table 7). For total PCDF concen-  trations as well as for I-TEQ, positive and significant correlation coefficients were observed for ALT (GPT) and AST (GOT) as well as for CHOL. Because of the well known associations between liver enzyme activity, serum cholesterol level, and alcohol intake, a multiple regression analysis was performed (Table 8). I-TEQ correlated significantly only with serum ALT (GPT) activity (p< 0.05). The correlation between I-TEQ and serum cholesterol is not significant (p= 0.063). These results may indicate an exposure-response relationship. However, statistically significant results do not necessarily reflect causality.
Our results must be discussed in the context of other publications. Note that PCDD/PCDF can cause liver damage in humans in high doses [reviewed by the World Health Organization (5)]. However, in the case of low PCDD/PCDF exposure, relevant effects on liver function are questionable. To our knowledge there are no data on liver toxicity of PCDF in humans. According to the tissue-as well as enzymespecific relative potency, 2,3,4,7,8-penta-CDF has the highest hepatotoxic potency of the furans (9). PCDF, however, were not increased in our study subjects (Figure 1).
In a group of 138 former chemical workers  with high TCDD exposure, none of the liver function indicators (AST, ALT, GGT) were significantly correlated with current and backcalculated TCDD concentration (13,15). In a total of 281 former workers of a trichlorophenol production plant, a significantly elevated risk of an out-of-range GGT was found only for persons with a history of significant alcohol consumption (14).
In conclusion, workers in nonferrous metal recycling plants may be exposed to dust contaminated with PCDF and to a lesser degree with PCDD. To prevent increased exposure, technical and personal preventive measures should be applied to reduce inhalation of dust and fumes originating from thermal processes. Statistical associations found between internal PCDD/PCDF exposure indicators and some liver parameters as well as cholesterol in serum should be reevaluated in a follow-up study.