Search

A urinary trichloroacetic acid (TCA) concentration of 100 mg/l at the end of the last work shift (8 h/day, 5 days/week) of the week has been established in workers as exposure equivalent for the carcinogenic substance trichloroethene (EKA for TRI) at an exposure concentration of 50 ppm TRI. Due to the continuous reduction of atmospheric TRI concentrations during the last years, the quantitative relation given by the EKA for TRI is revised for exposures to low TRI concentrations. A physiological two-compartment model is presented by which the urinary TCA concentrations are calculated that result from inhaled TRI in humans. The model contains one compartment for trichloroethanol (TCE) and one for TCA. Inhaled TRI is metabolized to TCA and to TCE. The latter is in part further oxidized to TCA. Urinary elimination of TCA is modeled to obey first order kinetics. All required model parameters were taken form the literature. In order to evaluate the model performance on the urinary TCA excretion at low exposure concentrations, predicted urinary TCA concentrations were compared with data obtained in two volunteer studies and in one field study. The model was evaluated at exposure concentrations as low as 12.5 ppm TRI. It is demonstrated that the correlation described by the hitherto used EKA for TRI is also valid at low TRI concentrations. For TRI exposure concentrations of 0.6 and 6 ppm, the resulting urinary TCA concentrations at the end of the last work shift of a week are predicted to be 1.2 and 12 mg/l, respectively.

To evaluate an adequate strategy for biological monitoring of aluminium (Al), a group of 62 Al welders (age in 1999: 23-51 years, median 35 years) was surveyed annually from 1999 to 2003 by determination of pre- and post-shift Al in urine and plasma. Biomonitoring was supplemented by personal air measurements of the total dust concentration. The welders' internal exposure was compared to the exposure of 60 non-exposed assembly workers (age in 1999: 21-51 years, median: 36 years) who were surveyed in 1999, 2001 and 2003. Having a nearly constant dust exposure, median concentrations of Al in urine (Al in plasma) of the welders decreased from 40.1 microg/g to 19.8 microg/g creatinine (8.7 to 4.6 microg/l). For the control group the median levels of Al in urine (plasma) ranged from 4.8 microg/g to 5.2 microg/g creatinine (2.4-4.3 microg/l) indicating a higher sensitivity for the marker Al in urine. No systematic differences have been found between pre- and post-shift internal exposure. This might be caused by the slow elimination kinetics and low systemic bioavailability of Al. A correlation analysis did not yield close relationships between dust exposure, Al in plasma and Al in urine underlining the importance of biomonitoring for assessment of Al exposure.

Carcinogenic chemicals in the work area are currently classified into three categories in section III of the German List of MAK and BAT Values (list of values on maximum workplace concentrations and biological tolerance for occupational exposures). This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these categories - IIIA1, IIIA2, IIIB - be retained as Categories 1, 2, and 3, to correspond with European Union regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, these three categories are supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not contribute significantly to risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. Chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures, are classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics, and for which risk at low doses can be assessed are classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented.

Carcinogenic chemicals in the work area are currently classified into three categories in Section III of the German List of MAK and BAT Values. This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these Categories--IIIA1, IIIA2, and IIIB--be retained as Categories 1, 2, and 3, to conform with EU regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, it is now proposed that these three categories be supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not convey a significant risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. It is proposed that chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures be classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics and for which risk at low doses can be assessed will be classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented. The proposed changes in classifying carcinogenic chemicals in the work area are presented for further discussion.

Evaluation of occupational or environmental risk due to exposure to chemicals requires sufficient information on the toxic profiles, mechanisms of action, toxicokinetics, dose-response relation, exposure, and the target dose. Usually exposure is estimated by measuring concentrations of the agent in air, food, water, soil, dust, or other media with which a population or an individual is in contact. However, this external exposure is only a rough estimate for the internal exposure (agent dose or its metabolite at the critical target in the organism). Factors of influence are bioavailability of the chemicals, variations in concentrations and routes of exposure, physical activity, and individual variation in rates of metabolism, distribution, and excretion. All these affect the concentration of the toxic agent at the critical target, which is the most precise information for risk assessment. Thus, internal exposure is best measured by determining the concentration of the toxicant or its ultimate metabolite at the critical site in the target organ or by determining adducts with cellular macromolecules such as proteins, amino acids, DNA, or its bases. The latter are easily available in experimental toxicology from animal experiments but only occasionally from humans. For health surveillance such data usually are not available, because they require invasive procedures such as biopsies. Therefore, more accessible body fluids or tissue are used, such as blood, urine, or adipose tissue, or adducts with macromolecules such as albumin or hemoglobin in the blood, DNA adducts in peripheral lymphocytes, or altered DNA bases in urine such as 8-hydroxyguanine. All of these are indicators for exposure, whereas risk can only be estimated if the correlation between their deviations from normal and the dose-response at the critical target is known.

A field study was carried out on 13 workers exposed to styrene vapors at time-weighted average concentrations between 10 and 73 ppm. The reactive intermediate styrene-7,8-oxide was determined in blood samples using a direct gas chromatographic method. Styrene-7,8-oxide concentrations were in the range between 0.9 and 4.1 micrograms/l blood. Linear correlations were found between styrene-7,8-oxide in blood and styrene in ambient air and blood. For an exposure concentration of 20 ppm styrene (German MAK value) a steady-state level of about 1 microgram styrene-7,8-oxide/l blood was calculated.