Comparative toxic potency ranking of chlorophenols: Pepelko, William E ;Gaylor, David W ;Mukerjee, Debdas
doi: 10.1191/0748233705th204oapmid: N/A
Chlorophenols are prevalent in all media of the environment. The most common environmental source of pentachlorophenol (PCP) and other chlorinated phenols are via the lumber industry as a wood preservative and as a pesticide in plant production. The US Environmental Protection Agency’s (EPA) contaminant candidate list (CCL) includes a majority of these compounds as unregulated contaminants. Except for pentachlorophenol, there is a lack of human or animal data base which can be used for human health risk assessment. The specific aim of this study is to develop a rationale to use in vivo nonmammalian, in vitro mammalian and nonmammalian, micro-organism toxicity data base, structural activity, mechanistic and toxicokinetic data bases for developing a relative toxic potency ranking scheme of chlorophenols. Although the toxic potency of chlorophenols was found to increase with the number of chlorines, the potency decreases if the chlorines are attached in the ortho position of the molecules. Based on the LOAELs and mammalian in vitro data, the relative potency of chlorophenols determined to be best estimated by the ratios of log Kow to the 0.55 power. The relationship of the toxic potency derived from such an approach is largely presumptive.
Use of QEESI© questionnaire for a screening study in Japan: Hojo, Sachiko ;Yoshino, Hiroshi ;Kumano, Hiroaki ;Kakuta, Kazuhiko ;Miyata, Mikio ;Sakabe, Kou ;Matsui, Takako ;Ikeda, Koichi ;Nozaki, Atsuo ;Ishikawa, Satoshi
doi: 10.1191/0748233705th219oapmid: N/A
QEESI© (Miller and Prihoda, 1999a: Toxicology and Industrial Health, 15, 370) was applied to 498 subjects, recruited from the general population of Miyagi prefecture, Japan, who had not been diagnosed previously as having multiple chemical sensitivity (MCS) or sick building syndrome. Seventeen (3.8%) of 440 subjects who returned valid completed questionnaires were classified as having symptoms ‘very suggestive’ of MCS using the four-classification system of Miller and Prihoda (1999a). We conducted detailed telephone interviews with these 17 individuals. All were visiting local hospitals on an outpatient basis with diagnoses other than MCS and had either current or previous presumed chemical exposure. Therefore, we recommended they undergo a medical check by MCS medical experts and indoor air quality assessment. Seven subjects participated in both the medical check and indoor air quality monitoring, six subjects participated in indoor air quality monitoring only and four subjects participated in neither. The seven subjects who participated in both the medical check and monitoring were diagnosed as having MCS by the above expert physicians. In nine houses of 13 subjects who participated in indoor environmental quality (IEQ) survey, acetaldehyde (9/9), formaldehyde (8/9), total volatile compounds (TVOCs) (6/9) and paradichlorobenzene (3/9) levels were above the respective guideline values for indoor air concentrations, outlined by the Ministry of Health, Labor and Welfare of Japan and were presumed to act as factors contributing to the subjects’ hypersensitivity and onset or development of symptoms. These results suggested that there might still be a population of patients not properly diagnosed as having MCS by clinicians in Japan. Therefore, we verified the efficacy of QEESI (Japanese version) for screening of MCS patients. The results of indoor air quality analysis suggested the manifestation and deterioration of MCS in Japan might be precipitated by indoor air pollutants, such as formaldehyde, acetaldehyde, volatile compounds (VOCs) and paradichlorobenzene.
Circulating levels of interleukin-18 in asbestos-exposed workers: Gangemi, Sebastiano ;Rapisarda, Venerando ;Minciullo, Paola Lucia ;Di Pasquale, Giuseppe ;Lombardo, Giuseppe ;Valentino, Matteo ;Fenga, Concettina
doi: 10.1191/0748233705th221oapmid: N/A
Occupational exposure to asbestos has been associated with the development of pulmonary diseases through a persistent inflammatory response initiated by reactive oxygen species and the subsequent release of proinflammatory mediators such as interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-a. Recently, IL-18, a pleiotropic proinflammatory cytokine and potent inducer of gene expression and synthesis of INF-g, TNF-a and IL-1 in immunocompetent cells, has been described. IL-18 serum concentrations were measured in 20 asbestos-exposed workers and in a group of 20 healthy donors. The workers underwent physical examination, pulmonary function tests and high-resolution computed tomography (HRCT). IL-18 levels were assayed in peripheral blood using the immunoenzymatic method with a commercial kit. The pulmonary function tests revealed a restrictive ventilatory deficit in nine (45%) cases and an obstructive ventilatory deficit in five (25%). The remaining six (30%) workers exhibited normal spirometric values. HRCT findings were: bilateral pleural plaques in 8 (40%) workers and bilateral parenchymal fibrosis in 12 (60%), with mean scores of 2.559 / 1.89. The exposed workers displayed significantly higher IL-18 concentrations than controls and those with parenchymal fibrosis displayed significantly higher values than workers with pleural plaques (P=0.001). In subjects with parenchymal fibrosis, HRCT scores significantly correlated with serum levels of IL-18 (P=0.001). Although the mechanisms leading to IL-18 release in asbestosis are unknown, the present preliminary results underscore the potential role of this cytokine in the pathogenesis of pulmonary toxicity.
Cytotoxicity of organotin compounds in different cultured cell lines: Hoth, Annett ;Johannisson, Reiner ;Ali, Sarwar Syed ;Schulze, Johannes ;Siegers, Claus-Peter
doi: 10.1191/0748233705th220oapmid: N/A
Organotin as monobutyltin (MBT), dibutyltin (DBT) and tributyltin (TBT) compounds are used as fungicides and anti-fouling compounds; small amounts are added to the new European Euro bills. Little is known about the toxicological profile of these compounds uptake and metabolism. We, therefore, studied the cytotoxicity of these agents in different cell lines, i.e., liver HepG2, renal LLCMK2 and ocular CEC cells. As a measure of cell growth and death, the neutral red assay and the release of LDH into the medium were used. IC50 values for growth inhibition by TBT were calculated as 160 nM in LLC-MK2, 150 nM in HepG2 and 180 nM in CEC cells; for DBT the corresponding values were higher, i.e., 500 nM DBT for LLC-MK2 cells, 300 nM for HepG2 cells and 220 nM for CE cells. ED50 values for LDH release indicating disturbances of the outer cell membrane was > 250 nM for TBT and > 350 nM for DBT in all cells. MBT was not toxic in concentrations up to 500 nM. Electron microscopic studies of cells treated with 300 nM tributyltin indicated severe mitochondrial damage with much less effect seen in other cell structures. We conclude that no differences exist between different cell lines that may serve as examples of tissues relevant for organotin exposure (eye), metabolism (liver) and specific metalloid damage (kidney). Growth inhibition was affected at organotin concentrations between 150 and 500 nM. This concentration is approximately 70-200 fold higher than values estimated in environmental samples.