Improvement in the GC–MS method for determining urinary toluene-diamine and its application to the biological monitoring of workers exposed to toluene-diisocyanate

Objectives: To develop a simple and sensitive GC–MS method for determining toluene-diamine (TDA) in urine and to apply the method for biological monitoring of workers exposed to toluene-diisocyanate (TDI). Methods: After acid hydrolysis of 0.1 ml of urine, diluted tenfold with water, for 1.5 h, the free TDA formed was extracted with dichloromethane, and the heptafluorobutyric anhydride derivative was determined by GC–MS. We applied the method to the biological monitoring of 18 workers who were using an 80:20 mixture of 2,4-TDI and 2,6-TDI. Results: 2,6-TDA and 2,4-TDA were simply determined in 7 min by GC–MS. TDA levels in post-shift urine were well correlated with personal exposure levels of TDI. The correlation was improved by correction with creatinine or specific gravity in the 2,6-isomer, but not in the 2,4-isomer because of low exposure levels. From the correlation equation, the 2,6-TDA level (corrected with creatinine), corresponding to the TDI level of 5 ppb, was calculated to be 31.6 g/g Cre. TDAs in pre-shift urine also correlated significantly with the personal exposure levels of TDIs, although the slope of the correlations for pre-shift samples was 60%–70% of those for post-shift samples. The correlation between 2,4-TDA and 2,6-TDA levels was significant, although the levels of the 2,4-isomer were less than one-tenth of the 2,6-isomers in both air (personal exposure) and urine. Conclusion: The present method is simple and practicable and can be useful for biological monitoring of TDI workers.     

Biological monitoring of isocyanates and related amines

Summary Two men were exposed to toluene diisocyanate (TDI) atmospheres at three different air concentrations (ca. 25, 50 and 70g/m³) . The TDI atmospheres were generated by a gas-phase permeation method, and the exposures were performed in an 8-m³ stainless-steel test chamber. The effective exposure period was 4h. The isomeric composition of the air in the test chamber was 30% 2,4-TDI and 70% 2,6-TDI. The concentration of TDI in air of the test chamber was determined by an HPLC method using the 9-(N-methyl-amino-methyl)-anthracene reagent and by a continuous-monitoring filter-tape instrument. Following the hydrolysis of plasma and urine, the related amines, 2,4-toluenediamine (2,4-TDA) and 2,6-toluenediamine (2,6-TDA), were determined as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas chromatography using selected ion monitoring (SIM) in the electron-impact mode. In plasma, 2,4- and 2,6-TDA showed a rapid-phase elimination half-time of ca. 2–5 h, and that for the slow phase was > 6 days. A connection was observed between concentrations of 2,4- and 2,6-TDI in air and the levels of 2,4- and 2,6-TDA in plasma. The cumulated amount of 2,4-TDA excreted in the urine over 24 h was ca. 15%–19% of the estimated inhaled dose of 2,4-TDI, and that of 2,6-TDA was ca. 17%–23% of the inhaled dose of 2,6-TDI. A connection was found between the cumulated (24-h) urinary excretion of 2,4- and 2,6-TDA and the air concentration of 2,4- and 2,6-TDI in the test chamber. A connection was also observed between the rate of urinary excretion of 2,4- and 2,6-TDA over the last 2h of exposure and the air concentration of 2,4- and 2,6-TDI in the test chamber. Biological monitoring of exposure to monomeric 2,4- and 2,6-TDI by the analysis of 2,4- and 2,6-TDA in biological media is feasible. A method based on 24-h urine sampling and determination levels of 2,4- and 2,6-TDA in hydrolysed urine is recommended. However, exposure to TDI is often associated with aerosols containing polymeric TDI, and we do not know whether analysis of TDA in urine can also be used as a marker of exposure to TDI prepolymers.     

Internal exposure to organic substances in a municipal waste incinerator

Summary Fifty-three persons occupied in a municipal waste incinerator were examined with respect to their internal exposure to organic substances which may be produced during pyrolysis of organic matter. For this purpose the levels of benzene in blood, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in plasma, and mono- (MCPs), di- (DCPs), tri- (TCPs), tetra-(TECPs) and pentachlorophenol (PCP) and hydroxypyrene in urine were determined. For control purposes, 431 men and women were examined. Significantly higher values for the workers were found for the excretion of hydroxypyrene [median (m): 0.24vs 0.11 g/l; non-smokers], 2,4/2,5-DCP (m: 10.5 vs 3.9 g/l) and 2,4,5-TCP (m: 1.2 vs 0.8 g/l) and for the HCB level in plasma (m: 4.4 vs 2.8 g/l). For the concentrations of 4-MCP and 2,3,4,6/2,3,5,6-TECP, the controls had significantly higher concentrations in urine than did the workers in the incineration plant (m: 4-MCP 1.7 vs 1.2; 2,3,4,6/2,3,5,6-TECP: 1.2 vs 0.3 g/l). No significant differences between workers and controls were detected with respect to benzene in blood (m: 0.20 vs 0.28 g/l; non-smokers), 2,4,6-TCP and PCPs in urine (m: 0.85 vs 0.60 and 2.2 vs 2.2 g/l) or the levels of PCB congeners in plasma (m: 138, 153, 180: 5.6 vs 4.1 g/l). The elevated levels of hydroxypyrene, 2,4/2,5-DCP, 2,4,5-TCP and HCB in biological material may be related to the incineration of the waste. These elevations, however, are very small and are of interest more from the environmental than from the occupational point of view.     

Human exposure to volatile halogenated hydrocarbons from the general environment

Summary The objective of this study was to assess individual human exposure to volatile halogenated hydrocarbons (VHH) under normal environmental conditions by means of biological monitoring, i.e. by the measurement of these compounds or their metabolites in body fluids, such as blood, serum, and urine. Blood samples of 39 normal subjects without known occupational exposure to these agents were examined for the occurrence of VHH. The following compounds were present in quantifiable concentrations in 60 to 95% of the blood samples examined: chloroform (median 0.2 g/l; range < 0.1–1.7 g/l), 1,1,1-trichloroethane (median 0.2 g/l; range < 0.1–3.4 g/l), tetrachloroethylene (median 0.4 g/l; range < 0.1–3.7 g/l). Trichloroethylene could be detected in 31% of all blood samples (median < 0.1 g/l; range < 0.1–1.3 g/l). In addition, the levels of trichloroacetic acid (TCA) were determined in serum and 24-h urine samples of 43 and 94, respectively, normal subjects. TCA was present in measurable concentrations in all serum and urine samples examined. The median of the TCA levels in serum was 21.4 g/l (range 4.8–221.2 g/l) and in urine 6.0 g/24 h (range 0.6–261.4 g/24 h). The results are discussed in relation to data from the literature on human exposure to VHH from the general environment, i.e. via air, food, and water. The upper normal limits calculated from the results of this investigation can be used to detect even minor excessive exposures to VHH.     

Peroxidase-catalyzed oxidation of chlorophenols to polychlorinated dibenzo-p-dioxins and dibenzofurans

Chlorophenols are transformedin vitro to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/ Fs) by peroxidase-catalyzed oxidations. This is demonstrated with bovine lactoperoxidase as well as horseradish peroxidase, and with 3,4,5- and 2,4,5-trichlorophenol (TrCP). The yield of total PCDD/Fs with lactoperoxidase was 11 g per g 345-TrCP and 10 g per g 245-TrCP, of which 2,3,7,8-substituted PCDD/Fs constituted 8.5 and 2.2 g/g, respectively, corresponding to 0.85 and 1.2 g/g of Nordic TCDD-equivalents.     

Internal lead and cadmium exposure in 6-year-old children from western and eastern Germany

Lead and cadmium levels in blood and deciduous teeth (shed incisors only) of 6-year-old German children were determined in 1991 in a large epidemiological study carried out in rural and urban areas of western Germany (Duisburg, Essen, Gelsenkirchen, Dortmund, Borken) and eastern Germany (Leipzig, Halle, Magdeburg, Osterburg, Gardelegen, Salzwedel). In total, blood lead and cadmium levels of 2311 German children and tooth lead and cadmium levels of 790 German children were analyzed. Blood lead levels were generally low in all study areas with geometric means between 39.3 g/1 and 50.8 g/l in the western German and between 42.3 g/1 and 68.1 g/l in the eastern German study areas. The mean blood lead level of Turkish children (n = 213) living in the western German study areas was 50.1 g/l and thus 5.6 g/1 higher than the overall geometric mean of the western German children. The higher exposure may be explained by a higher oral uptake from food and different living conditions. These children were excluded from multiple regression analysis because they were all living in the western study areas. The mean tooth lead levels ranged between 1.50 and 1.74 g/g in the western and between 1.51 g/g and 2.72 g/g in the eastern study areas. Thus, they show a distribution pattern similar to blood. Blood and tooth lead levels were higher in urban than in rural areas and higher in the eastern German than in the western German study areas. With regard to the blood and tooth cadmium concentrations, no significant differences between the study areas could be found. The mean cadmium levels in blood ranged between 0.12 g/1 and 0.14 g/l and the mean tooth cadmium concentrations between 20.8 ng/g and 27.8 ng/g. Blood and tooth lead and cadmium levels of the eastern and western German children were thus mainly at a relatively low level in all rural and urban study areas. The study demonstrates and confirms that blood and tooth lead levels are influenced by several demographic, social, and environmental variables. The results indicate that there has been a further significant decrease of lead and cadmium exposure in western German children since our last epidemiological study carried out in the same study areas in 1985/1986.     

Blood styrene concentrations in a “normal” population and in exposed workers 16 hours after the end of the workshift

Summary Blood styrene was measured by a gas chromatography-mass spectrometry method in 81 normal people and in 76 workers exposed to styrene. In the normal subjects, styrene was also tested in alveolar and environmental air. Styrene was found in nearly all (95%) blood samples. Average styrene levels in the normal subjects were 221 ng/1 in blood (Cb), 3 ng/1 in alveolar air (Ca) and 6 ng/1 in environmental air (Ci). Styrene levels did not differ significantly between smokers and non-smokers, 95% of values being below 512 ng/1 in Cb, 7 ng/1 in Ca and 15 ng/l in Ci. In workers with an average exposure to styrene of 204 g/l, at the end of the workshift, mean blood styrene concentration was 1211 g/l. In blood samples collected at the end of the Thursday shift, styrene levels were significantly higher (1590 g/1) than those found at the end of the Monday shift (1068 g/l. A similar difference was found in samples taken the morning after exposure (60 and 119 g/l, respectively). Significant correlations between blood and environmental styrene were found both at the end of the shift and the morning after exposure (r=0.61 and 0.41, respectively). In workers occupationally exposed to styrene, 16 h after the end of the workshift, blood styrene (94 g/l) was significantly higher than that found in the normal subjects (0.22 g/l). The half-life of blood styrene was 3.9 h.     

Nitrous oxide in blood and urine of operating theatre personnel and the general population

Nitrous oxide (N₂O) was assayed in 676 urine samples and 101 blood samples provided after exposure by operating theatre personnel from nine hospitals. The blood and urine assays were repeated in 25 subjects 18 h after the end of exposure. For 80 subjects, environmental N₂O was also measured during intraoperative exposure. Mean urinary N₂O in the 676 subjects at the end of exposure was 40 g/l (range 1–3805 g/l); in 10 of the 676 subjects, urinary N₂O was in the range 279–3805 g/l (mean 1202 /l). The 98^th percentile was 120 g/l. Mean blood N₂O at the end of exposure, measured in 101 subjects, was 21 g/l (median 16 g/l, range 1–75 g/l). Blood and urine N₂O (1.5 g/l and 4.9 g/l, respectively) in 25 subjects, 18 h after exposure, was significantly higher than in occupationally non-exposed subjects (blood 0.91 g/l, urine 1 g/l). Environmental exposure was significantly related to blood and urinary N₂O (r = 0.59 andr = 0.64, respectively). Blood and urinary N₂O were significantly related to each other (r = 0.71), and were equivalent to about 25% of the environmental exposure level. The mean urinary N₂O of 1202 g/l in 10/676 subjects was not related to environmental exposure in the operating theatre. The highest urinary N₂O levels measured in these 10/676 subjects could be explained by an asymptomatic urinary infection.     

Biological monitoring of occupational exposure to toluene diisocyanate

Summary The study validated the use of urinary toluene diamine (TDA) in postshift samples as an indicator of preceding 8-h exposure to toluene diisocyanate (TDI). Nine workers exposed in TDI-based polyurethane foam production were studied. Their exposure levels varied in 8-h time-averaged samples from 9.5 to 94 g/m³. The urinary TDA concentrations varied from 6.5 to 31.7g/g creatinine and they were linearly related to the atmospheric TDI levels. Approximately 20% of TDI is metabolized to diamines but their specificity is remarkable to the extent that by analysis for the 2,4- and 2,6-diamino isomers an idea of the percutaneous absorption may be had.     

Biological and environmental monitoring of occupational exposure of pharmaceutical plant workers to methotrexate

Summary The exposure of 11 pharmaceutical plant workers to methotrexate (MTX) was studied. Personal air samples were taken during the different manufacturing processes: drug compounding, vial filling, and tablet preparation. The uptake of MTX was established by the determination of MTX in urine. MTX was analyzed using the fluorescence polarization immunoassay (FPIA), a method that is frequently used for monitoring serum levels in patients treated with MTX. The FPIA method was modified in such a way that MTX could be measured quickly and efficiently in air and urine samples. MTX was detected in air samples of all workers except for those involved in the vial filling process (range: 0.8–182 g/m³; median: 10 g/m³). The highest concentrations were observed for workers weighing MTX (118 and 182 g/m³). MTX was detected in urine samples of all workers. The mean cumulative MTX excretion over 72–96 h was 13.4 g MTX-equivalents (range: 6.1–24 g MTX-equiva g MTX-equivalents (range: 6.1–24 g MTX-equivalents). lents). A significantly lower background level of 10.2 g A significantly lower background level of 10.2 g MTX-equivalents was measured in urine of 30 control persons (range: 4.9–21 g MTX-equivalents).     

Toxicity of aldicarb and fonofos to the early-life-stage of the fathead minnow

Flow-through early-life-stage (ELS) toxicity tests were conducted with the pesticides aldicarb (Temik^®) and fonofos (Dyfonate^®) to determine their effect on the survival and growth of fathead minnows. Concentrations of 78g/L of aldicarb and 16g/L of fonofos did not affect survival and growth. However, 156g/L of aldicarb and 33g/L of fonofos were lethal to larval-juvenile exposed for 30 days post-hatch. The maximum acceptable toxicant concentration (MATC) of aldicarb and fonofos for the fathead minnow is estimated to be between 78–156g/L and 16–33g/L, respectively. The corresponding chronic values (geometric mean of MATC values) would be 110g/L and 23g/L. Acute toxicity tests gave 96-hr LC50 values of 1370g aldicarb/L and 1090g fonofos/L. The acute-chronic ratio (96-hr LC50/chronic value) is 12 for aldicarb and 47 for fonofos.     

Biological effects of Kepone and mirex in freshwater invertebrates

Acute and chronic toxicity studies of Kepone^® (chlordecone) and mirex were conducted with daphnids (Daphnia magna), amphipods (Gammarus pseudolimnaeus), and larvae of a midge (Chironomus plumosus). Acute toxicities of Kepone ranged from a 48-hr EC50 of 350g/L for midges to a 96-hr LC50 of 180g/L for amphipods, whereas the acute toxicities of mirex to all three taxa exceeded 1000g/L. Maximum acceptable toxicant concentrations (MATC's) for Kepone and mirex were estimated by measuring reproduction of daphnids, growth of amphipods, emergence of midges, and survival of all organisms. MATC for Kepone was estimated to be between 9 and 18g/L for daphnids, between 1 and 2g/L for amphipods, and between 8.4 and 18g/L for midges; MATC for mirex exceeded 34g/L for daphnids and midges, but less than 2.4g/L for amphipods. The concentration of Kepone and mirex accumulated by daphnids was 760 and 8025 times, respectively, the concentration in water. Estimated times for elimination of 50% of the residues by daphnids were 141 hr for Kepone and 12 hr for mirex.     

Forestry workers involved in aerial application of 2,4-dichlorophenoxyacetic acid (2,4-D): Exposure and urinary excretion

Urinalysis was conducted on six volunteer workers involved in mixing and loading 2,4-D ester solutions into aircraft and in guiding the spray aircraft in two conifer release programs during 1981 and 1982. Exposures were reduced by wearing a full line of protective clothing. Two females and one male were involved in mixing the spray for 109 aircraft loads over an 11-day period in 1981. During the 1981 operation, the highest daily excretion of 2,4-D in the urine was 0.30, 0.94 and 9.59 g/kg body weight for the three workers. In 1982, three male workers were involved, one diluting the concentrated solution and loading the aircraft, and two marking the swaths for aerial application over an 18 day period. The highest daily excretion of 2,4-D in the urine was 7.73, 8.37, 22.2 g/kg body weight for the three workers. One of the authors, acting as a bystander, was directly sprayed in the 1982 season and 0.44% was absorbed based on urine analysis. The highest daily excretion of 2,4-D in his urine was 4.75 g/kg body weight. For all seven people, the calculated exposure was less than the no-effect level of 10 mg/kg of body weight/day by a large margin of safety. The presence of 2,4-D in urine samples in the pre-spray period and its slow disappearance during the post spray period prompted further investigation. Swabs of internal surfaces of living quarters revealed deposits of 2,4-D from 0.7 to 288 g/0.1m² and on spray equipment from 0.7 to 184 g/0.1m².     

Current external and internal exposure to naphthalene of workers occupationally exposed to polycyclic aromatic hydrocarbons in different industries

Objectives: External and internal exposure to naphthalene was examined in the most important industries that are typically concerned with polycyclic aromatic hydrocarbon (PAH)-induced diseases (cancer). Furthermore, a control collective from the general population was investigated. Methods: External naphthalene was determined by personal air sampling (n=205). The internal exposure was examined by urinary metabolites 1-naphthol and 2-naphthol (n=277). Results: Highest median concentrations of naphthalene in air were found in converter infeed (93.2 g/m³) and coal-tar distillation (35.8 g/m³). Moderate and low levels were determined in coking plants (14.5 g/m³) and in the production of refractories (6.1 g/m³) and graphite electrodes (0.7 g/m³). Biological monitoring revealed concentrations of the sum of both metabolites [(1+2)-NOL] in smokers to be increased by 1.6–6.4 times compared with that in non-smokers at the same workplaces. Among non-smokers we found high median (1+2)-NOL levels in converter bricklayers (120.1 g/l), in coal-tar distillation workers (56.0 g/l) and in coking plant workers (29.5 g/l). (1+2)-NOL concentrations around 10 g/l were found in the production of refractories and graphite electrodes. There was a rough coherency between external and internal naphthalene exposure. In the controls, median (1+2)-NOL concentrations were 10.9 g/l in non-smokers urine and 40.3 g/l in smokers urine samples. Conclusions: Actual conditions of occupational hygiene at the workplaces investigated in this comprehensive study are better than those that current limit values of 50,000 g/m³ (TLV, TRK) seem to induce. It has become obvious that tobacco smoking is a crucial confounding factor in biological monitoring of naphthalene-exposed humans, making interpretation of occupationally increased naphthol excretions very difficult at low exposure levels.     

Blood toluene as a biological index of environmental toluene exposure in the “normal” population and in occupationally exposed workers immediately after exposure and 16 hours later

Blood toluene was measured in a group of 100 workers occupationally exposed to a mean 8-h environmental toluene concentration of 128 g/l (34 ppm), and in a group of 269 normal subjects without occupational exposure to toluene. The mean blood toluene of the workers at the end of the shift and the following morning, after 16 h, was 457 and 38 g/l, respectively. The normal subjects had a blood toluene level of 1.1 g/l. On the basis of the highly significant correlation between blood toluene and occupational exposure, it can be calculated that environmental toluene exposure of 188 and 377 g/l (50 and 100 ppm) gives end-of-shift blood toluene levels of 690 and 1390 g/l, respectively. The corresponding blood toluene levels on the following morning are 50 and 100 /l, respectively.     

Blood acetone concentration in “normal people” and in exposed workers 16 h after the end of the workshift

Summary Acetone levels were measured by gas chromatography mass spectrometry (GC-MS) in environmental and alveolar air, blood and urine of 89 non-occupationally exposed subjects and in three groups of workers exposed to acetone or isopropanol. Acetone was detected in all samples from non-exposed subjects, with mean values of 840 g/l in blood (Cb), 842 g/l in urine (Cu), 715 ng/l in alveolar air (Ca) and 154 ng/l in environmental air (Ci). The ninety-fifth percentiles were 2069 g/l in Cb, 2206 g/l in Cu and 1675 ng/l in Ca. The blood/air partition coefficient of acetone was 597. Correlations were found in Cb, Cu and Ca. In specimens sampled at the end of the workshift from subjects occupationally exposed to acetone, a correlation was found in the blood, urine, alveolar and environmental air concentrations. The blood/air partition coefficient of acetone was 146. On average, the blood acetone levels of workers were 56 times higher than the environmental exposure level, and the concentration of acetone in alveolar air was 27% more than that found in inspiratory air. The half-life for acetone in blood was 5.8 h in the interval of 16 h between the end of the workshift and the morning after. The morning after a workshift with a mean acetone exposure of 336 g/l, blood and urinary levels were 3.5 mg/l and 13 mg/l, respectively, which were still higher than those found in normal subjects. It can be concluded that endogenous production of acetone and environmental exposure to acetone or isopropanol do not affect the reliability of biological monitoring of exposed workers, even 16 h after low exposure.     

Short-term exposure of zooplankton to the synthetic pyrethroid,fenvalerate, and its effects on rates of filtration and assimilation of the alga,Chlamydomonas reinhardii

In acute tests of toxicity, two cladocerans,Daphnia galeata mendotae andCeriodaphnia lacustris, and the calanoid,Diaptomus oregonensis, were more sensitive to fenvalerate thanDaphnia magna, the organism used in standard laboratory bioassays. The 48-hr EC₅₀s for each species/stage in order of increasing sensitivity were adultD. magna — 2.52 g/L;D. magna (48-hr old) — 0.83 g/L; adultD. galeata mendotae — 0.29 g/L; adultC. lacustris — 0.21 g/L;D. galeata mendotae (48-hr old) — 0.16 g/L; adultDiaptomus oregonensis — –0.12 g/L. No toxicity was observed when these organisms were exposed to a range of concentrations of the emulsifiable concentrate without fenvalerate (the EC blank).Rates of filtration of the¹⁴C-labelled alga,Chlamydomonas reinhardii byD. galeata mendotae, C. lacustris andD. oregonensis were decreased significantly at sublethal concentrations of fenvalerate after only 24-hr exposure.Ceriodaphnia lacustris showed the greatest sensitivity with rates of filtration significantly decreased at 0.01 g fenvalerate/ L. Concentrations of fenvalerate 0.05 g/L resulted in decreased rates of filtration byD. galeata mendotae. A concentration of 0.10 g fenvalerate/ L caused rates of filtration to increase inD. oregonensis. whereas 0.05 and 0.5 g/L resulted in a decrease in these rates.Rates of assimilation of algae byD. galeata mendotae, C. lacustris andD. oregonensis exposed to similar concentrations of fenvalerate were decreased at concentrations 0.05 g fenvalerate/L. Changes in rates of assimilation were not as sensitive a parameter of toxicity as changes in rates of filtration. The EC blank had no significant effects on rates of filtration or assimilation for all three species.     

Toxicity of the herbicides 2,4-D,DEF, propanil and trifluralin to the Dungeness crab,Cancer magister

Lethal and sublethal responses to the herbicides 2,4-D, DEF®, propanil, and trifluralin of various life history stages of the Dungeness crab,Cancer magister, were examined to estimate maximum acceptable toxicant concentrations (MATC) of each compound for this species. Zoeae were found, in long term tests, to be the most sensitive stage. Based on the experiments with this stage, MATCs were concluded to be >0.95, <6.9g for DEF, 26, <220g/L for trifluralin, 80, < 1,700g/L for propanil, and < 1,000g/L for the free acid form of 2,4-D.Technical Paper No. 4819, Oregon Agricultural Experiment Station     

Synthetic Musk Toxicity to Early Life Stages of Zebrafish (<Emphasis Type="Italic">Danio rerio</Emphasis>)

Synthetic musk substances have been found in a number of environmental samples. Some of these chemicals have been detected in concentrations above 1 g/L in water, which raises concern about possible effects on aquatic life. The toxicity of four synthetic musks, 4-tert-butyl-2,6-dimethyl-3,5-dinitrophenylethanone (musk ketone), 1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene (musk xylene), 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthalenyl)ethanone (AHTN, tonalide) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-[g]-2-benzopyrane (HHCB, galaxolide), were studied in zebrafish by the use of two different early life-stage methods. In the first method, specific developmental characteristics during the first 48 hours were studied. In the second method, hatching and survival times were studied on eggs and larvae. The results on heart rate in the first test gave the following LOECs: musk ketone 10 g/L, musk xylene and AHTN 33 g/L, and HHCB showed no effect up to 1000 g/L. In the study of survival time, LOEC for musk ketone was 100 g/L, for musk xylene 33 g/L, and AHTN gave no effect on survival time up to 100 g/L. The LOECs for musk ketone, musk xylene, and AHTN in this study are in the range of what has been measured in sewage effluents and recipients, and consequently these substances may have adverse impact on wild fish.     

Assessment of thyroid,testes, kidney and autonomic nervous system function in lead-exposed workers

Summary The objective of the study was to assess whether moderate occupational exposure to lead may be associated with early changes in potential target organs (thyroid, testes, kidney, autonomic nervous system). Workers exposed to lead in a lead acid battery factory (n = 98; mean blood lead 51 g/dl, range 40–75 g/dl) and 85 control workers were examined. None of the indicators of kidney function (in urine: retinol-binding protein, ₂-microglobulin, albumin,N-acetyl--d-glucosaminidase; in serum: creatinine, ₂-microglobulin), endocrine function (follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, thyroxine, triiodothyronine) and autonomic nervous system (R-R interval variations on the electrocardiogram) were correlated with lead exposure (blood lead or duration of exposure) or showed significantly different mean values between the exposed group and controls. These results and an assessment of the published data suggest that compliance with the Directive of the Council of the European Communities on lead exposure (health surveillance in workers whose lead in blood exceeds 40 g/dl and removal from exposure when blood lead exceeds 70–80 g/dl) would prevent the occurrence of significant biological changes in the majority of lead-exposed workers.