Activity Patterns Applied to Pollutant Exposure Assessment: Data from a Personal Monitoring Study in Los AngelesSchwab, Margo; Colome, Steven D.; Spengler, John D.; Ryan, P. Barry; Billick, Irwin H.
doi: 10.1177/074823379000600601pmid: N/A
There have been many recent advances in exposure assessment methods. Studies of the spatial and temporal distribution of pollutants (Ott and Eliassen 1973; Wright et al. 1975; Cortese and Spengler 1976) and the contribution of indoor sources (NAS 1980; Spengler and Sexton 1983; Yocum 1982) have led us away from models that predict exposure solely on the basis of concentrations recorded by regional fixed-site monitors to those that incorporate concentrations recorded in various indoor and outdoor environments. Most recently, emphasis has focused on the concept of total human exposure. If exposure is defined as the intersection between a person and a pollutant concentration (Ott 1982), total exposure can be conceptualized as a function of the time spent in contact with various pollutant concentrations. A basic supposition underlying this concept of total human exposure is that people's activity patterns (the locations they visit, when they visit them, and what they do there) influence their exposure to pollutants.
Chloropentafluorobenzene: Short-Term Inhalation Toxicity, Genotoxicity and Physiologically-Based Pharmacokinetic Model DevelopmentKinkead, Edwin R.; Wall, Henry G.; Hixson, Clifford J.; Tice, Raymond R.; Kutzman, Raymond S.; Vinegar, Allen
doi: 10.1177/074823379000600602pmid: N/A
Ten Fischer 344 rats and six B6C3F1 mice of each sex were exposed to air, 0.25, 0.80, or 2.50 mg chloropentafluorobenzene (CPFB)/liter of air for three weeks, excluding weekends. Exposure to 2.50 mg/liter caused a reduction in the growth rate of rats but did not affect the growth rate of mice. Following the exposure there was reduced SGOT activity in the blood serum of exposed rats and a dose related increase in liver weights. Increased liver weights were observed in mice as well; the response in the female groups was clearly dose dependent. Histologically the livers of both rats and mice presented single cell necrosis. In exposed mice hepatocytes exhibited mild hepatocytomegaly with increased granular eosinophilic cytoplasm. In evaluations for its potential to induce chromosomal damage following this exposure regimen, CPFB did not alter the rate of bone marrow cellular proliferation. Assessment of the micronucleated polychromatic erythrocytes and normochromatic erythrocyte populations during the inhalation exposures indicated a general absence of genotoxic activity.
Molecular Properties and Inhibition Kinetics of Acetylcholinesterase Obtained from Rat Brain and Cockroach GanglionSingh, Ashok K.
doi: 10.1177/074823379000600603pmid: N/A
1. The molecular composition of acetylcholinesterase (AChE) obtained from cockroach neural, and rat brain tissues was different. Vertebrate enzyme exhibited a higher degree of polymerization than insect enzyme.2. Acephate was a potent inhibitor of cockroach AChE, but a poor inhibitor of rat AChE. Unlike acephate, methamidophos was a potent inhibitor of both cockroach and rat enzymes. Acephate exhibited greater affinity for the cockroach-AChE than for the rat-AChE, and acephate phosphorylated the cockroach-AChE several times faster than the rat enzyme. The rate of phosphorylation of insect and rat AChE was similar in the presence of methamidophos. Solubilization of AChE by Triton X-100 altered the kinetics of inhibition of rat AChE by acephate. However, solubilization did not alter the kinetics of inhibition of rat AChE by methamidophos or the kinetics of inhibition of cockroach AChE by acephate or methamidophos.3. The mechanism of acephate-cockroach AChE interaction was different than the mechanism of acephate-rat AChE interaction. It is proposed that both the rat and cockroach enzyme may contain, along with the anionic and esteratic sites, an “electron deficient” (ED) binding site which may exhibit selectivity for acephate and nefopam. The ED site in rat-AChE has allosteric properties, whereas the cockroach-AChE does not. It is also proposed that the ED site in cockroach-AChE may be situated in or adjacent to the active site and, therefore, acephate may be bound to the ED site such that the phosphate moiety of acephate interacts with the enzyme's “esteratic” site. Although nefopam also bound to the ED site in cockroach AChE, it did not inhibit the enzyme. This study also indicated that the ED site in rat-AChE may be peripheral to the active site, and that the binding of acephate to this site prevented the phosphorylation by methamidophos of the rat-AChE. Unlike acephate, methamidophos specifically bound to the active site in both the rat- and cockroach-AChE.
Chemical Functionalities at the Silica Surface Determining its Reactivity when Inhaled. Formation and Reactivity of Surface RadicalsFubini, Bice; Giamello, Elio; Volante, Marco; Bolis, Vera
doi: 10.1177/074823379000600604pmid: N/A
Reactive radicals at the surface of quartz or other SiO2 poly- morphs have been studied by EPR in relation to their possible role in pathogenicity. All the examined dusts bear the character- istic radicals of silica ground in air: Si, SiO, SiO2 (peroxyradi- cal) and O2 (superoxide ion), but some also show additional spectral lines belonging to other radical forms. Comparison of standard quartz dusts (DQ-12, Min-u-sil 5) with a natural quartz and with what obtained by grinding a very pure quartz crystal indicates that to a higher purity corresponds a higher rad- ical population. Cristobalite and vitreous silica exhibit similar spectra, with larger proportion by respect to quartz, of partially reduced oxygen forms. The reactivity of the silica surface to- wards O2 and NaClO aqueous solutions are investigated by ex- amining the modification in the EPR spectra induced by these treatments. A possible mechanism for fibrogenicity is proposed whereby, within the activated macrophage, a catalytic reaction occurs between surface functionalities and macrophage oxygen metabolites. This reaction would trigger the abnormal produc- tion of fibroblast stimulating factors, ending up with silicosis.
The Carcinogenic Activity of Commercial Grade Toluene Diisocyanate in Rats and Mice in Relation to the Metabolism of the 2,4- and 2,6-Tdi IsomersDieter, M.P.; Boorman, G.A.; Jameson, C.W.; Matthews, H.B.; Huff, J.E.
doi: 10.1177/074823379000600605pmid: N/A
Groups of 50 F344/N rats of each sex and 50 B6C3F1 mice of each sex were gavaged with corn oil or a mixture of toluene di- isocyanate (TDI) in corn oil for 5 days per week for 105 or 106 weeks. Female rats and mice were given doses of 60 or 120 mg/ kg body weight, while male rats received 30 or 60 mg/kg, and male mice received 120 or 240 mg/kg. The TDI reacted with the moisture in the corn oil vehicle resulting in doses that were 10% to 23% below the target dose concentrations.The chemical product used was commercial grade TDI, which was an 80%-20% mixture of the 2,4- and 2,6-isomers. Chemical disposition and metabolism studies were conducted with each of the radiolabelled TDI isomers in male rats. Absorption of both of the TDI isomers occurred, with the highest concentrations found in the stomach, cecum, large intestine, and bladder. Ex- cretion occurred via the feces and urine. The major metabolic products from the metabolism of 2,4-TDI were shown to be identical with those from the metabolism of the carcinogen, 2,4- diaminotoluene, whereas the metabolism of the 2,6-TDI isomer yielded one major product, identified as 2,6- bis(acetylamino)toluene.Greater than 10% depression in body weight gain occurred in all dosed groups of rats throughout most of the study. The major non-neoplastic lesions that were observed in both sexes of the TDI-exposed rats were dose-related increases in acute broncho- pneumonia, characterized as chemical pneumonitis, with inci- dences as high as 50%. In mice mean body weight gain was depressed in dosed male and in high dose females. The principle non-neoplastic lesion in mice that was attributed to chemical treatment was cytomegaly of the kidney tubular epithelium in males.Survival in all groups of dosed rats was significantly lower than in controls. A dose-dependent pattern of mortality did not com- mence until 70 weeks of exposure, demonstrating that toluene di- isocyanate elicited a cumulative toxic response. There was also significantly lower survival in high dose male, but not female mice, by comparison to controls.Despite the reduction of power and sensitivity in the rat studies caused by early mortality, statistically significant increases in tu- mor incidences were observed in many different target organs. TDI was carcinogenic in F344/N rats, causing subcutaneous fi- bromas and fibrosarcomas in males and females, pancreatic aci- nar cell adenomas in males, and pancreatic islet cell adenomas, neoplastic nodules of the liver, and mammary gland tumors in females. TDI was not carcinogenic in male mice, but caused he- mangiomas or hemangiosarcomas and hepatocellular adenomas in female B6C3F1 mice.The pattern of multiple tumor induction caused by administra- tion of the commercial grade TDI was very similar to that found in previous studies of the carcinogen, 2,4-diaminotoluene. The specific target sites of carcinogenicity in the 2,4-diaminotoluene study were all seen in the 2,4-(80%) and 2,6-(20%) TDI study as well. Metabolic studies of these compounds showed that com- mon metabolites were produced from the 2,4-TDI isomer and from 2,4-diaminotoluene, indicating that the 2,4-isomer in the commercial grade TDI was probably responsible for the carcino- genic activity.
Asbestos-Related Radiographic Abnormalities in Public School CustodiansOliver, L. Christine; Sprince, Nancy L.; Greene, Reginald
doi: 10.1177/074823379000600607pmid: N/A
A cross-sectional prevalence study of 120 public school custodians was carried out to investigate the prevalence of asbestos-related disease and to determine the proportion with disease attributable to asbestos exposures in school buildings. Medical and occupational histories, flow-volume loops, and posterior-anterior, lateral, and anterior oblique (AO) chest radiographs were obtained. Single breath DLCO was measured and chest auscultation performed. The present report describes radiographic abnormalities and associations with exposure. Mean age of subjects was 57 years and mean duration of work as a custodian, 27 years. Fifty-seven (47.5%) had no known or likely exposure to asbestos outside of their work as a school custodian (NOE). Pleural plaques (PP) occurred in 40 (33%) of the total group and 12 (21%) of the group with NOE. Multivariate analysis revealed significant associations (p < 0.05) between PP and duration of asbestos exposure. The proportion with PP increased with increasing years of latency. AO radiographs increased PP detection by a factor of 1.9. Our results reveal PP prevalence in excess of background in the study population and indicate that PP are attributable to asbestos exposure in schools in a subset with NOE. Prudent management of asbestos in buildings is indicated for the prevention of related disease.