Journal of Toxicology and Environmental Health

Hjelm, Ewa Wigaeus; Näslund, Per H.; Wallén, Maria

doi: 10.1080/15287398809531197pmid: 3172270

To study the influence of cigarette smoking on the toxicokinetics of toluene, 10 habitual smokers who intended to stop smoking were exposed to toluene vapor (3.2 mmol/m 3 , 4 h) at three different exposure occasions: (I) while the smoking habit was still ongoing, and (II and III) 1 and 3–4 wk, respectively, after the day at which the smoking habit was discontinued. Solvent concentrations in the exhaled air and in the blood as well as hippuric acid concentrations in the urine were measured during the exposure period and for 3 h after the exposure period. The apparent clearance of toluene decreased significantly (p < 0.05) 3–4 wk after the smoking habit was discontinued. This decrease was not a consequence of the increased body weight noticed in the subjects. No statistically significant differences between the three exposure occasions in the elimination rate of hippuric acid could be demonstrated. Thus, cigarette smoking seems to enhance the elimination rate of toluene from the body, since the apparent clearance was decreased after smoking was stopped.

Mautz, William J.; Kleinman, Michael T.; Phalen, Robert F.; Crocker, T. Timothy

doi: 10.1080/15287398809531198pmid: 3172271

Respiratory tract injury resulting from inhalation of mixtures of ozone (O3) and nitrogen dioxide (NO 2 ) and of O 3 and formaldehyde (HCHO) was studied in Sprague‐Dawley rats under exposure conditions of rest and exercise. Focal inflammatory injury induced in lung parenchyma by O 3 exposure was measured morphometrically and HCHO injury to the nasal respiratory epithelium was measured by cell turnover using tritium‐labeled thymidine. Mixtures of O 3 (0.35 or 0.6ppm) with NO 2 (respectively 0.6 or 2.5 ppm) doubled the level of lung injury produced by O 3 alone in resting exposures to the higher concentrations and in exercising exposures to the lower concentrations. Formaldehyde (10 ppm) mixed with O 3 (0.6 ppm) resulted in reduced lung injury compared to O 3 alone in resting exposures, but exercise exposure to the mixture did not show an antagonistic interaction. Nasal epithelial injury from HCHO exposure was enhanced when O 3 was present in a mixture. Mixtures of O 3 and NO 2 at high and low concentrations formed respectively 0.73 and 0.02 ppm nitric acid (HNO 3 ) vapor. Chemical interactions among the oxidants, HNO 3 , and other reaction products (N 2 O 5 and nitrate radical) and lung tissue may be the basis for the O 3 ‐NO 2 synergism. Increased dose and dose rate associated with exercise exposure may explain the presence of synergistic interaction at lower concentrations than observed in resting exposure. No oxidation products were detected in O 3 ‐HCHO mixtures, and the antagonistic interaction observed in lung tissue during resting exposure may result from irritant breathing pattern interactions.

Kowal, Norman E.

doi: 10.1080/15287398809531199pmid: 3050141

Urinary cadmium and beta2‐microglobulin concentrations from approximately 1000 samples from the general adult U.S. population, collected as part of the National Health and Nutritional Examination Survey II (NHANES II), were related to nutritional and smoking history of the individuals. Urinary cadmium concentration was negatively correlated with dietary iron (significance level of 0.0065), negatively correlated with dietary calcium (significance level of <0.0001), and significantly (level of <0.001) higher in past or present smokers than in those who had never smoked. The results suggest increased cadmium absorption in the presence of low dietary intake of iron, low dietary intake of calcium, and cigarette smoking in the general population of the United States.

Olaniran, Nurudeen S.; Karol, Meryl H.

doi: 10.1080/15287398809531200pmid: 3172272

A guinea pig animal model of byssinosis has been described that demonstrates both acute and chronic effects of cotton dust inhalation (Ellakkani et al., 1984, 1987). During the latter study in which guinea pigs were exposed to 21 mglm 3 cotton dust 5 d/wk, 6 h/d for 52 wk, blood samples were taken from animals (20 exposed, 20 sham‐exposed) prior to exposure and monthly during the exposure period. Sera were evaluated for quantities of the major protein fractions, and for IgG antibodies to cotton dust components. At the completion of the study, blood was evaluated for total and differential leukocytes. At 6 mo of exposure, each of the five protein fractions was significantly different from the corresponding fraction in the control animals. Antibodies reactive with an aqueous cotton dust extract (ACDE) were prominent by 2 mo of exposure and the titer was increased with continued exposure. The extract was composed of 2.6% protein, 12.8% reducing sugar, and 4.1% nucleic acid, with the remainder being largely simply sugars and inorganic material. A fraction of the antibodies showed reactivity with gram‐negative bacteria and specifically with Entero‐bacter agglomerans, the most prevalent gram‐negative microorganism in the dust. Minimal antibody response was detected using lipopolysaccharide from this microorganism or gram‐positive bacteria. These results indicate that exposure of guinea pigs to cotton dust resulted in hematologic changes and in specific antibody formation. The presence of antibodies in each of the animals suggests their possible use as an indicator of cotton dust exposure.

Rao, M. S.; Subbarao, V.; Scarpelli, D. G.

doi: 10.1080/15287398809531201pmid: 3050142

Transdifferentiation is a process in which one differentiated cell type is converted to another. A unique example of transdifferentiation is the development of hepatocytes from pancreatic cells in adult hamsters and rats. In this communication we report the induction of pancreatic hepatocytes in hamsters that were given 2,3,7,8‐tetrachlorodi‐benzo‐p‐dioxin (TCDD). Two or 6 intraperitoneal (ip) injections of TCDD at a dose of 100 μg/kg body weight at 4‐wk intervals induced pancreatic hepatocytes in 75% and 89% of the animals respectively. In animals given only two doses of TCDD each pancreas contained one to two hepatic foci, whereas when six injections were administered multiple hepatic foci were observed. By hematoxylin and eosin stain and by periodic acid Schiff stain, the pancreatic hepatocytes were morphologically identical to those in normal liver. Although the exact mechanism by which TCDD induces the transformation is not clear, it is conceivable that TCDD acting through receptor‐mediated mechanisms is activating the repressed liver‐specific genes in the pancreas.

Kodavanti, Prasada Rao S.; Mehrotra, Bam D.; Chetty, Sreeramulu C.; Desaiah, Durisala

doi: 10.1080/15287398809531202pmid: 2845111

Previous reports from our laboratory and others clearly indicated that organochlorine insecticides such as chlordecone and DDT are potent inhibitors of ATPases involved in active ion transport. The present studies were initiated to study the effect of plic‐tran, chlordecone, toxaphene, aldrin, dieldrin, endrin, isodrin, and telodrin on enzymes involved in cyclic AMP metabolism. Rat brain synaptosomes were prepared by Ficoll‐sucrose gradient centrifugation method. Adenylate cyclase activity, which is involved in anabolism of cAMP, was determined using the radioactive method by measuring [ 32 P]cAMP formed during hydrolysis of [ 32 P]ATP. Phosphodiesterase activity, which is involved in the catabolism of cAMP, was estimated by measuring [ 3 H]adenosine formed using [3H]cAMP as a substrate. Synaptosomal adenylate cyclase activity was inhibited significantly by plictran with an IC50 of 25 μM, and a maximum inhibition of 30% was observed with 50 μM chlordecone. Toxaphene, aldrin, dieldrin, endrin, isodrin, and telodrin did not affect the adenylate cyclase activity. Similarly, none of the insecticides studied inhibit the activity levels of synaptosomal phosphodiesterase. The significant inhibition of adenylate cyclase observed with plictran might be due to the tin component, since several heavy metals affect cAMP metabolism. The lack of inhibition of adenylate cyclase and phosphodiesterase with other compounds tested clearly supports our postulation that these organochlorine insecticides exert their neurotoxic action by the selective inhibition of ATPases in synaptosomes.

Leach, Glenn J.; Russell, R. David; Houpt, John T.

doi: 10.1080/15287398809531203pmid: 3172273

Initial toxicological safety evaluations of the insect repellent N,N‐diethyl‐m‐tolua‐mide (DEET) indicated a potential hypotensive effect. The current study was initiated in order to pursue this aspect of DEET toxicity and to elucidate potential mechanisms for this response. Sublethal intraperitoneal injections of DEET in anesthetized rats were found to decrease mean blood pressure and heart rate in a dose‐related fashion. Doses ranged from 56 to 225 mg/kg. Dogs treated with 225 mg/kg of DEET exhibited a similar hypotension and bradycardia. Cardiac output was also significantly reduced but stroke volume and total peripheral resistance were not altered. Lead II ECG changes included small increases in P‐R and Q‐T intervals. In a series of pharmacological studies in rats, DEET was found to decrease the hypotension and bradycardia associated with acetylcholine injection; epinephrine, norepinephrine, and histamine responses were not altered. Atropine pretreatment reduced but did not eliminate the hypotensive effects of DEET.

Burger, Joanna; Gochfeld, Michael

doi: 10.1080/15287398809531204pmid: 3172274

One‐day‐old herring gulls (Larus argentatus) were injected intraperitoneally with lead nitrate solution (0.1 or 0.2 mg Pb/g) or sterile saline to examine differences in growth rates. Despite the low levels of lead exposure, by d 8 there were significant differences in growth rates as a function of treatment. There were also, by d 8, significant differences in bill length, tarsus length, and wing bone length. Except for bill length, these differences persisted for the duration of the study. Developmental curves varied, with lead‐treated birds reaching the same asymptote as control birds for bill length, but having a lower asymptote for tarsus length. For curves where asymptotes were reached, lead‐treated birds required more days to reach it than control birds. The initial amount of food eaten each day was positively correlated with weight gain for control birds, but negatively correlated for lead‐treated birds.

Shi, Xianglin; Dalai, N. S.; Vallyathan, V.

doi: 10.1080/15287398809531205pmid: 2845112

Electron spin resonance (ESR) spectrum of the hydroxyl (• OH) radical spin adduct with the spin trap 5,5‐dimethyl‐1‐pyrroline‐N‐oxide has been obtained in suspensions of freshly ground quartz particles. The concentration of the spin adduct (and hence of the • OH radicals) increases with the amount of grinding. The dust's potential for the generation of the • OH radicals is maximum when fresh (i.e., immediately after grinding) and decreases to 50% in about a day on storage in air. Studies involving metal chelates indicate that the • OH radical formation involves mainly the silica surface and H 2 O rather than the Fenton reaction. The results suggest that hydroxyl radical reaction(s) could be important in the lipid peroxidation and fibrogenicity by quartz dust, particularly in acute silicosis.

Richters, Amis; Damji, Karim S.

doi: 10.1080/15287398809531206pmid: 3050143

The effects of ambient levels of NO2 on murine splenic T‐lymphocyte subpopulations and natural killer cells were investigated. AKR/cum and C57BL/6) mice were exposed, in inhalation chambers, to 0.25 ppm NO2 for 7 wk and 0.35 ppm NO3 for 12 wk, respectively. Monoclonal antibody technology was used in conjunction with fluorescence‐activated cell sorter (FACS) analysis to detect quantitative changes in total T‐lymphocytes (Thy‐1.2‐positive), mature T‐lymphocytes (Lyt‐1‐positive), T‐helperlin‐ducer lymphocytes (L3T4‐positive), T‐cytotoxic/suppressor lymphocytes (Lyt‐2‐positive), and natural killer cells (asialo GM1‐positive). Percentages of all T‐lymphocyte subpopulations tested and natural killer cells were lower in spleens of mice exposed to NO2 compared to filtered‐air controls. This is the first report providing evidence linking alterations in T‐lymphocyte subpopulations and natural killer cells to NO2 exposure at ambient levels. Changes in T‐lymphocyte subpopulations detected by FACS and correlated to impaired immune function may provide an extremely sensitive means of demonstrating NO2‐induced changes in the immune system.