bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Pulmonary Response of Asthmatics to 3.0 PPM Formaldehyde
Authors: Sauder Larry R. , Green Donald J. , Chatham Marie D. , Kulle Thomas J.
Published: September 2013

Previous studies have failed to demonstrate bronchoconstriction in unselected asthmatics after brief (≤ 1/2-h), controlled exposures to formaldehyde (HCHO). This study was designed to evaluate the acute pulmonary response to 3 ppm HCHO in nine nonsmoking asthmatic volunteers over a more relevant exposure duration (3 hrs). Pulmonary function, nonspecific airway reactivity and symp toms were assessed before and at intervals during the exposure. No significant changes in pulmonary function (FVC, FEV1 , FEF 25-27%, SGaw, or FRC) or airway reactivity were observed. There was a significant increase in nose/throat irritation at 30 min. (P < 0.05) and in eye irritation at 60 min (P < 0.05) and 180 min (P < 0.01). These results suggest that individuals with asthma will not expe rience significant bronchoconstriction when exposed at rest to 3 ppm HCHO; however, most will experience eye and upper respira tory tract irritation.
The Acute Toxicity and Mutagenic Potential of 3-Methyl-2-Benzothiazolinone Hydrazone
Authors: Ballantyne Bryan , Slesinski Ronald S. , Myers Roy C.
Published: September 2013

3-Methyl-2-benzothiazolinone hydrazone (MBTH), widely used in analytical laboratories, was investigated for potential handling hazards. Tested as the hydrochloride, it was found to be of moderately high acute peroral toxicity with LD50 values in rabbits of 177 mg/kg (males) and 268 mg/kg (females), and in the rat 308 mg/kg (males) and 149 mg/kg (females). The major signs of toxicity, seen at peroral doses of 125 mg/kg and above, were convulsions. Although of low acute lethal percutaneous toxicity in rats (LD50> 16 g/kg), rabbits were more sensitive with one of five males dying at an applied dose of 16 g/kg, and females having an LD50 of 12.3 g/kg; convulsions were seen in rabbits having applied cutaneous doses of 4 g/kg and above. There was no evidence for cutaneous inflammation after a 4 hour occluded contact with MBTH in rabbits, although following 24 hour occlusive contact in the acute percutaneous toxicity study there was erythema, edema, desquamation and, in a few animals, local necrosis. Ocular studies in rabbits indicated that, depending on the degree of contamination, MBTH produced mild to moderate eye irritation. In keeping with its low vapor pressure, there were no adverse effects from a 6 hour exposure of rats to an atmosphere saturated with any vapor produced from solid MBTH at ambient temperature. MBTH was positive in an Ames bacterial mutagenicity assay, particularly in the absence of metabolic activation. These studies indicate MBTH to be of moderately high acute peroral toxicity, of moderate percutaneous toxicity, a mild primary skin irritant, a mild to moderate eye irritant, and produced mutations in Salmonella. There is a need for skin and eye protection, and avoidance of swallowing, when handling MBTH.
Influence of Glibenclamide On the Efficacy of Calcium Trisodium Pentetat as an Antidote for Cadmium Toxicity
Authors: Tewari Prakash C. , Tandon Sushil K.
Published: September 2013

Cadmium causes hyperglycemia, activation of hepatic and renal gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-diphosphatase, increases hepatic and renal zinc, renal copper and decreases hepatic and renal iron levels in rats. Glibenclamide, a hypoglycemic agent, significantly reversed most of the Cd effects, enhanced fecal excretion of Cd and potentiated urinary and fecal elimination of Cd by calcium trisodium diethylenetriaminepentaacetate (CaNa3DTPA), a commonly used metal chelator. However, the restoration of Cd-induced alterations in carbohydrate metabolism was not related to elimination of Cd from the tissues.
Hematologic Effects of Benzene: a Thirty-Five Year Longitudinal Study of Rubber Workers
Authors: Kipen Howard M. , Cody Ronald P. , Crump Kenny S. , Allen Bruce C. , Goldstein Bernard D.
Published: September 2013

We studied over 17,000 peripheral blood counts, accumulated during surveillance from 1940 through 1975, from a cohort of 459 benzene-exposed workers. Linear regressions demonstrated significant decreases in white and red cell counts, as well as hemoglobin, for workers exposed during the 1940's, without persistent trends over the ensuing 25 years. Strongly positive correlations were observed between these blood count fluctuations and fluctuations in retrospective estimates of benzene exposures for this plant for the earlier periods of surveillance (mean estimated exposure 1940 to 1948, 75 ppm), but not for later years (mean estimated exposure 1948 to 1975, 15 to 20 ppm). These data suggest substantial limitations of hematologic examination of populations to detect abnormalities in populations currently exposed to benzene. The data also demonstrate a novel approach to the biological validation of exposure estimates based upon limited industrial hygiene and historical record data.
The Metabolism of Mono-(2-Ethylhexyl) Phthalate (Mehp) and Liver Peroxisome Proliferation in the Hamster
Authors: Lhuguenot J.C. , Mitchell A.M. , Elcombe C.R.
Published: September 2013

This study has investigated the in vivo metabolism of mono-(2-ethylhexyl) phthalate (MEHP), the initial metabolite of di-(2-ethylhexyl) phthalate in mammals, and the hepatic peroxisome proliferation induced by this compound following multiple oral administration to hamsters. Hamsters received [14C]-MEHP, by gavage, at doses of 50 and 500 mg/kg body wt on each of three consecutive days. Urine was collected every 24 hours and metabolite profiles were determined using capillary gas-chromatography. Multiple high doses of MEHP (500 mg/kg) induced a change in the relative proportions of metabolites produced. As previously reported for the rat, metabolites derived from sequential ω-following by β-oxidation were increased. This increase was correlated with a parallel 3-fold increase in peroxisomal β-oxidation-a marker for peroxisome proliferation. Hamsters were less responsive than rats to peroxisome proliferation elicited by MEHP. In contrast to the rat, a large proportion of hamster ω-1 oxidation products of MEHP (metabolites 6 and 9, mono (2-ethylhexyl-5-oxohexyl) phthalate and mono (2-ethyl 5-hydroxyhexyl) phthalate, respectively) were found as their glucuronide conjugates. This metabolic species difference may relate to differences in sensitivity to MEHP as a peroxisome proliferator. The relationship between metabolite conjugation, peroxisome proliferation and production of ω-oxidation metabolites is discussed.
Carcinogenic Risk Assessment in Proper Perspective
Authors: Upton Arthur C.
Published: September 2013

The evidence that human cancers result in large measure from factors related to life style, working conditions, or other extrinsic variables-and are thus, in principle, preventable (Doll and Peto, 1981)—and the hypothesis that there is no threshold for the carcinogenic effects of many cancer-causing agents (Office of Science and Technology Policy, 1985) have spurred efforts to minimize human exposure to carcinogens. In pursuit of this goal, attempts have been made to identify airborne and other extrinsic carcinogens and to assess the extent to which they contribute to the occurrence of cancer. The status of such endeavors is summarized in the following, without any attempt at a comprehensive review, which would be beyond the scope of this report.
Repeated Laboratory Ozone Exposures of Volunteer Los Angeles Residents: an Apparent Seasonal Variation in Response
Authors: Linn William S. , Avol Edward L. , Shamoo Deborah A. , Peng Ru-Chuan , Valencia Lupe M. , Little David E. , Hackney Jack D.
Published: September 2013

This study was intended to help explain individual differences in susceptibility to irritant effects of ozone (O3), by determining whether prior ambient O3 exposures and/ or recent acute respiratory illness modified response to laboratory 03 exposures. Response was measured in terms of lung function changes and irritant symptoms. Initially, 59 adult volunteer Los Angeles area residents underwent screening exposures in spring, before the season of frequent high ambient O3 levels. Unusually responsive and nonresponsive individuals (N = 12 and 13 respectively) underwentfollowup exposures in autumn (late in the high-O3 season) and in winter (low-O3 season). All exposures were to 0.18 ppm O3 for 2 hr with intermittent heavy exercise at 31° C and 35% relative humidity. Nonresponders tended to remain nonresponsive throughout. In fall, responders had lost much of their reactivity, as if they had "adapted" to summer ambient 03 exposures. They did not regain reactivity by winter. Clinical laboratory findings suggestive of acute respiratory illness did not appear to correlate with O3 response. Eight responders and 9 nonresponders underwent another followup exposure in spring, about 1 yr after screening. By that time most responders had regained their reactivity; individual function changes were significantly correlated with changes 1 yr earlier. These results suggest that response to O3 is a persistent individual characteristic, but can be modified by repeated ambient exposures.
The Pulmonary Effects of Ozone and Nitrogen Dioxide Alone and Combined in Healthy and Asthmatic Adolescent Subjects
Authors: Koenig Jane Q. , Covert David S. , Smith Michael S. , Van Belle Gerald , Pierson William E.
Published: September 2013

Separate exposures to 0.12 ppm ozone (O3) or 0.18 ppm nitrogen dioxide (NO2) have not demonstrated consistent changes in pulmonary function in adolescent subjects. However, in polluted urban air, O3 and NO2 occur in combination. Therefore, this project was designed to investigate the pulmonary effects of combined O3 and NO2 exposures during intermittent exercise in adolescent subjects. Twelve healthy and twelve well-characterized asthmatic adolescent subjects were exposed randomly to clean air or 0.12 ppm O3 and 0.30 ppm NO2 alone or in combination during 60 minutes of intermittent moderate exercise (32.51 /min). The inhalation exposures were carried out while the subjects breathed on a rubber mouthpiece with nose clips in place. The following pulmonary functional values were measured before and after exposure: peak flow, total respiratory resistance, maximal flow at 50 and 75 percent of expired vital capacity, forced expiratory volume in one second and forced vital capacity (FVC). Statistical significance of pulmonary function changes was tested by analysis of covariance for repeated measures. After exposure to 0.12 ppm 03 a significant decrease was seen in maximal flow at 50% of FVC in asthmatic subjects. After exposure to 0.30 ppm NO2 a significant decrease was seen in FVC also in the asthmatic subjects. One possible explanation for these changes is the multiple comparison effect. No significant changes in any parameters were seen in the asthmatic subjects after the combined O3-NO2 exposure or in the healthy subjects after any of the exposures.
Chronic Toxicity Tests of Sodium Thiocyanate With Sodium Nitrite in F344 Rats
Authors: Lijinsky W. , Kovatch R.M.
Published: September 2013

Sodium thiocyanate, a common environmental chemical, was found to increase the incidence of liver tumors in a group of rats treated with 0.08% in drinking water. To test the possibility that thiocyanate was catalyzing the formation of carcinogenic nitrosamines from amines and nitrite in the food, a group of 20 male and 20 female rats was given a higher dose of sodium thiocyanate (0.32%) together with sodium nitrite (0.2%) in drinking water. Similar groups of rats were given 0.32% sodium thiocyanate or 0.2% sodium nitrite in drinking water or were untreated. All treatments lasted most of the lifetime of the rats, at least 2 years. There was no difference between the groups, treated or untreated, in survival, or in the incidence of any tumor that could be related to the treatment. The results indicate that sodium thiocyanate is without carcinogenic activity in rats, alone or combined with sodium nitrite.
Contact Hypersensitivity Response To Glutaraldehyde in Guinea Pigs and Mice
Authors: Stern Malvin L. , Holsapple Michael P. , McCay J. Ann , Munson Albert E.
Published: September 2013

Glutaraldehyde has a wide spectrum of uses which can result in dermal contact with the agent. The low number of reports of hypersensitive reactions to glutaraldehyde indicates a low incidence of sensitization. This paper describes the contact hypersensitivity response to glutaraldehyde in the guinea pig and the mouse. Female albino Hartley strain guinea pigs and female B6C3F1 mice were sensitized with 0.3, 1.0 and 3.0% glutaraldehyde and challenged with 10% glutaraldehyde. Doses of glutaraldehyde were selected from assays for primary irritancy. Guinea pigs received 100 μl by direct dermal application, for 14 consecutive days, and mice received 20 μl by direct dermal application, for 5 or 14 consecutive days, to sites prepared by shaving and dermabrading. Rest periods were 7 or 14 days for guinea pigs and 4 or 7 days for mice. Measurement of the contact hypersensitivity response in guinea pigs was both visual evaluation (scoring) at 24 and 48 hours following challenge and radioisotopic assay at 48 hours, and in mice by radioisotopic assay 48 hours after challenge. Both guinea pigs and mice demonstrated dose-dependent contact hypersensitivity responses to glutaraldehyde. The radioisotopic assay appeared to be more sensitive than visual evaluation in detecting contact allergic hypersensitivity to glutaraldehyde.
The Acute Toxicity of Tris(Dimethylamino) Silane
Authors: Ballantyne Bryan , Dodd Darol E. , Myers Roy C. , Nachreiner Donald J. , Pritts Irvin M.
Published: September 2013

The acute handling hazards of tris(dimethylamino)silane [TDMAS] were investigated. The acute male rat peroral LD50 (with 95% confidence limits) was 0.71 (0.51-0.97) ml/kg, and the acute male rabbit percutaneous LD 50 was 0.57 (0.35-0.92) ml/ kg. The liquid was severely irritating to the rabbit eye and skin, and the vapor severely irritating to the rat eye. The dynamically generated saturated vapor Lt50 in female rats was 12 (9.7-15) min. The effect of varying the atmospheric concentration of vapor from TDMAS on acute inhalation toxicity was investigated by passing ordinary moist air countercurrent to liquid TDMAS metered into a slightly heated glass tube. Based on nominal concentrations, the 4 hr-LC50 for vapor from TDMAS was 734 (603-893) ppm in female rats by this procedure. Stoichiometrically, this accords with toxicity due to liberation of dimethylamine (DMA)from TDMAS. In a subsequent study designed to assess the influence of relative humidity on vapor toxicity, nitrogen was passed over heated liquid TDMAS and the resultant atmosphere was introduced into the air intake duct of the inhalation exposure chamber. Gas chromatographically measured TDMAS concentrations (± SD) were 395 ± 111, 127 ± 25, 62 ± 8 and 23 ± 21 ppm; the corresponding DMA vapor concentrations were 112 ± 171, 31 ± 43, 10 ± 6 and 26 ± 44 ppm. The 4-hr LC50 (males and females) was 38 (34-43) ppm TDMAS vapor. Thus, TDMAS is of moderate acute peroral and percutaneous toxicity, a severe primary skin and eye irritant, an aspiration hazard, and of high intrinsic acute inhalation toxicity, but in moist air conditions lethal toxicity may be reduced and in such circumstances DMA may be a significant factor in toxicity.
Quantification of Toxic Response and the Development of the Median Effective Dose (Ed 50)—a Historical Perspective
Authors: Piegorsch Walter W.
Published: September 2013

The development of the widely-used median effective (or lethal) dose as a summary measure in quantifying toxic response to chemical stimuli is reviewed. Attention is directed at those mathematical properties noted by the originator of the median effective dose, the English physiologist John William Trevan, that make the measure a useful summary statistic for toxicological studies. Consideration is also given to the development of precursor measures to the median effective dose, such as minimal effective dose.
Application of Pharmacokinetic Principles to Exposure to Chemical Mixtures
Authors: O'Flaherty Ellen J.
Published: September 2013

Kinetic interactions among chemicals present in a mixture can influence the relationship between administered and delivered or effective dose; these interactions are distinct from dynamic interac tions such as, for example, competition between two chemicals for receptor binding sites. The relationship between administered and effective dose depends on a number of biochemical, physiological, and physical factors such as age, sex, level of physical activity, route of administration, dose pattern, and bioavailability. In addi tion, interactions among chemicals may limit or increase the effec tive dose relative to the administered dose for any of the chemicals of a mixture. If the mechanism of the interaction is known, the direction and general magnitude of its effects may be predictable. A variety of potential interactions is briefly reviewed, and selected illustrations of these interactions are given. Two types of interac tions likely to be pervasive in mixtures of chemically related bioac tive materials are considered in greater detail. These interactions are induction of metabolizing enzymes such as the mixed-function oxidases, and competition of structurally similar chemicals for active sites on metabolizing enzymes. Simulations are presented to illustrate the consequences of these interactions, and examples of their occurrence are given.
Effect of a Metal Mixture in Diet On the Toxicokinetics and Toxicity of Cadmium, Mercury and Manganese in Rats
Authors: Kostial Krista , Blanu Maja , Maljkovi Teodora , Kello Dinko , Rabar Ivan , Stara Jerry F.
Published: September 2013

The purpose of this work was to determine whether a metal mix ture added to diet influences the toxicokinetics and toxicity of some elements.

The metal mixture (MM) used in these experiments was ash (slag) from a coal gasification plant. The effect of this mixture (5 percent in diet) on the toxicokinetic and on the acute or subchronic toxicity of Cd, Hg, Mn was determined in rats of different ages. Rats were exposed for five weeks in toxicokinetic and six weeks in acute tox icity experiments. Sucklings were exposed through their mothers, which received the MM in diet over the pregnancy and lactation period. In toxicokinetic studies, half of the animals additionally received Cd, Hg or Mn (100, 50 or 2000 ppm, respectively) in drinking water. In subchronic experiments, six-week-old albino rats of both sexes were given MM in the diet and Cd, Hg or Mn in drinking water for 16 weeks.

In toxicokinetic studies, 115mCd,203 Hg or 54Mn were administered orally or intraperitoneally to mothers and pups. Exposure to MM had no effect on the absorption, retention and organ distribution of these elements determined six days after radioisotope administra tion. In acute toxicity studies, exposure to MM in diet had no effect on LD50 values obtained eight days after oral administration of Cd, Hg or Mn to rats of different ages. In subchronic experi ments, the effect of individual metals (Cd, Hg or Mn) was similar in animals with and without simultaneous exposure to the metal mixture (only a slight potentiation of a few health-effect parameters of cadmium was noticed in some animals).

It is concluded that oral exposure to MM in the diet had almost no effect on the toxicokinetics and toxicity of Cd, Hg and Mn. This could be explained by the low level or low bioavailability of ele ments from MM, by the metal-metal interaction within the mixture or by the choice of health effect indicators determined. These results are presented as one of the potential approaches for study ing the health effect of a metal mixture as occurring in the environment.
Formaldehyde: An Experimental Multipotential Carcinogen
Authors: Soffritti Morando , Maltoni Cesare , Maffei Francesca , Biagi Roberta
Published: September 2013

Male and female Sprague-Dawley rats of different ages at the start of the experiments (12 day embryos, and 7 and 25 weeks old) were administered formaldehyde in drinking water at different doses (2,500 or 1,500, 1,000, 500, 100, 50, 10, 0 ppm).

An increased incidence of leukemias and of gastro-intestinal tu mors was observed in formaldehyde treated rats. Gastro-intestinal tumors are exceptionally rare in the rats of the colony used.

These results, together with the ones obtained by other Authors on rats exposed by inhalation to formaldehyde, indicate that this compound is an experimental multipotential carcinogen.

The experimental results presented in this report give scientific support to the epidemiological observation of a higher incidence of leukemias and of gastro-intestinal cancers among the people occu pationally exposed.
Health Effects of Gasoline Refueling Vapors and Measured Exposures At Service Stations
Authors: Page Norbert P. , Mehlman Myron
Published: September 2013

Liquid gasoline is a complex mixture of at least 150 hydrocarbons with about 60-70% alkanes (paraffins), 25-30% aromatics, and 6- 9% alkenes. In order to evaluate the potential for health effects from inhaling gasoline vapors, it is essential to understand the major differences in the composition of vapors versus liquid gaso line. The small chain, low carbon-numbered components are more volatile and thus in higher percentages in the vapor phase than the larger and heavier molecules.

It is noteworthy that the concentrations of aromatics (the more toxic of the gasoline components), are depleted to about 2% in the vapor phase, with the light paraffins (the less toxic) enriched to about 90%. Actual measurements of vapor exposure at service sta tions confirm that the vapor composition is primarily to low weight alkanes although benzene is also emitted and represents the chemi cal of greatest concern.

A perceived health concern from inhaling gasoline vapors is the potential for carcinogenicity based on the induction of kidney tumors in male rats and liver tumors in female mice exposed to wholly-vaporized gasoline. However, the results of the animal stud ies are of questionable relevance for human risk assessment due to the unique mechanism operative only in the male rat and since the exposure was to wholly-vaporized gasoline rather than the gasoline vapor mixture to which humans are exposed.

Recent research supports the hypothesis that branched-chain alkanes bind to a globulin specific to make rats, alpha 2-u-globulin. The protein complex can not be degraded in the usual manner so that protein accumulation occurs in renal cells, leading to cytotox icity, death, proliferation, and with prolonged exposure, kidney cancer. The results of epidemiology studies fail to link an increase in cancer to exposure to gasoline vapors.
The Determination of the Repeated Oral Toxicity of Halocarbon Oil, Series 27-S
Authors: Kinkead Edwin R. , Culpepper Brenda T. , Henry Sandra S. , Szotak Phyllis S. , Flemming Carlyle D. , Kutzman Raymond S. , Bruner Richard H. , Wyman John F. , Mattie David R.
Published: September 2013

Halocarbon 27-S (HC 27-S), a polymer of chlorotrifluoroethylene (CTFE), is used as a lubricating oil for pumps in hyperbaric chambers. Although monomeric CTFE has been shown to produce renal lesions in rats, the toxicity of CTFE polymers have not been investigated. To assess the toxicity of repeated exposure to HC 27–S, three groups (N = 6/group) of male and female Fischer-344 rats were dosed with 2.5 g HC 27-S/kg for 7 or 21 consecutive days. Groups were sacrificed at 7, 21, and 35 days (14 days after the 21-day dosing). Corresponding control groups (N = 6) were dosed with deionized water. Decreased water consumption and urine output were apparent in all test groups. Statistically significant increases in fluoride excretion were noted in 24-hr urine samples assessed periodically during the study. Neurotoxic signs were observed in female rats but not in male rats. Significant increases in liver and kidney weights were seen in all rats, regardless of number of dosing days. The increased fluoride burden in treated animals appeared sufficient to alter bone calcium/phosphate ratios in male rats but not female rats. Gross liver enlargement and hepatocellular cytomegaly indicated that the liver was probably the primary target organ following repeated administration of HC 27-S. (Supported by US Navy through Air Force Contract

# F33615-085-C-0532.)
Process Chemicals in the Oil and Gas Industry: Potential Occupational Hazards
Authors: Cottle Merva K.W. , Guidotti Tee L.
Published: September 2013

Numerous chemicals are used in various processes of the oil and gas industry: drilling, cementing, completion, stimulation, and production. The number and the complexity of composition of process chemicals has increased greatly over the last three decades. The occupational hazards of exposure to these agents has received little attention. We reviewed the various processes in the industry, the type of chemicals used in each process, and some of their characteristics. We placed emphasis on those for which significant toxicity has been established or is suspected, and those for which there is incomplete information on their chemistry and health hazards. This report is intended to form a basis for a more complete survey of the process chemicals, and to draw attention to the possibilities for toxic exposure resulting from use of these agents in the oil and gas industry. The ultimate objective is to promote the safe use of these agents in the industry.
Short Term Toxicity of Nitrous Oxide on the Immune, Hemopoietic, and Endocrine Systems in CD-1 Mice
Authors: Healy Charles E. , Drown David B. , Sharma Raghubir P.
Published: September 2013

Occupational exposures to subanesthetic levels of N2O have been documented to result in suppressed proliferative cell activities. Male CD-1 mice were exposed to 0, 50, 500, and 5000 ppm of N2O for 6 hr/day, 5 days/week for 2 or 13 weeks. Tritiated-thymidine ([3H]-TdR) uptake was measured in CD-1 splenic lymphocytes cultured with and without mitogens and in a mixed lymphocyte culture (MLC). Antibody-mediated immunocompetency was determined for sheep red blood cell (SRBC)-sensitized animals by plaque forming cell (PFC) assay and serum anti-SRBC antibody (Ab) titer. Deoxyuridine suppression tests (dUrdST) were performed on bone marrow cells. There was significantly decreased splenic lymphocyte uptake of [3H]-TdR by cells cultured with mitogenic substances and in MLC following 2–week exposures to 5000 ppm. After 13–week exposures the animals' splenic lymphocytes showed increased [3H]-TdR uptake following high N2O dosing in both the mitogen-induced blastogenesis and MLC assays. Compared to control animals, the 5000 ppm exposure group had significantly depressed PFC activity and circulating anti-SRBC Ab levels following the 13-week N2O exposures, and all 13-week exposure groups demonstrated decreased liver weights and leukopenia. Bone marrow activity at these dosing levels was depressed in a dose-dependent fashion following 13-week gas exposures.
Multi-Route Exposure Assessment and Biological Monitoring of Urban Pesticide Applicators during Structural Control Treatments with Chlorpyrifos
Authors: Fenske Richard A. , Elkner Kenneth P.
Published: September 2013

A preliminary study of dermal and respiratory exposure to chlorpyrifos (DursbanR TC) during structural treatments was conducted with eight workers from a commercial pest control company. The compound was applied by sub-slab and soil injection to four houses, with each application involving two workers. Crawl space applications were included in three of the jobs. Field sampling extended over the entire workday, and included personal air samples and dermal exposure evaluation with patches and handwashes. A fluorescent tracer was added to the formulation for qualitative determination of skin deposition patterns. Pre-exposure and complete 72 hour urine samples were also collected. Total dermal exposure averaged 5.94 mg/hr. The major contributors were the upper legs (38%) and the forearms (34%). Accidents occurred during two of the four applications observed, and the two workers involved in the accidents were the most highly exposed individuals. The mean estimated absorbed daily dose was 9.5 ug/kg/day, with approximately 73% contributed by the dermal route. Thus, under these work conditions the Threshold Limit Value is not an appropriate guide for worker safety. The principal urinary metabolite of chlorpyrifos, 3,5,6-trichloro-2-pyridinol, was found in measurable quantities in all urine samples. Urinary metabolite levels collected 24–48 hr post-exposure were highly correlated (R2 = 0.86) with total absorbed dose estimates. The high variability among individual excretion patterns suggests against the use of urine spot sampling, but longer collections may prove useful in the development of a Biological Exposure Index for chlorpyrifos.
Subchronic Inhalation of Triethylamine Vapor in Fischer-344 Rats: Organ System Toxicity
Authors: Lynch D.W. , Moorman W.J. , Lewis T.R. , Stober P. , Hamlin R.D. , Schueler R.L.
Published: September 2013

Male and female F-344 rats were exposed at 0, 25, or 247 ppm triethylamine (TEA) vapor, 6 hr per day, 5 days per week for up to 28 weeks in order to characterize the subchronic organ system toxicity. Rats were weighed biweekly and scheduled sacrifices were performed following about 30, 60, and 120 days of exposure. No statistically significant treatment-related effects on organ weights, hematology, clinical chemistry, or electrocardiographic indices were observed. Body weight gain was not affected by TEA treatment. No physiologic or pathologic evidence of cardiotoxicity was seen in rats exposed to either TEA concentration for up to 28 weeks. No gross or histopathologic lesions attributable to TEA exposure were noted in any of the organs examined, including the nasal passages. This latter finding is in marked contrast to previously reported findings from this laboratory in which squamous metaplasia, suppurative rhinitis, and lymphoid hyperplasia were found in the respiratory epithelium of F-344 rats exposed to the structurally related chemical, diethylamine, under the same conditions as this study (Lynch et al., 1986).
The Reproductive and Developmental Toxicity of High Flash Aromatic Naphtha
Authors: Mckee Richard H. , Wong Zachary A. , Schmitt Susan , Beatty Patrick , Swanson Mark , Schreiner Ceinwen A. , Schardein James L.
Published: September 2013

Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent—High Flash Aromatic Naphtha. A program was initiated to assess the toxicological properties of High Flash Aromatic Naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted to assess the potential for developmental toxicity in the mouse and for reproductive toxicity in the rat.

In the developmental toxicity study in CD-I mice, exposure of dams by inhalation to near lethal levels (1500 ppm) resulted infetal mortality, reduced weight, delayed ossification, and an increased incidence of cleft palate. At 500 ppm, a level at which maternal weight gain was slightly reduced, fetal weight gain was also reduced, but there was no other evidence of developmental effects. The lowest exposure level (100 ppm) did not cause any maternal or developmental toxicity.

There was no consistent evidence of reproductive toxicity in rats, even at exposure levels which resulted in significantly reduced parental weight gain. In addition, when parental exposure was stopped on GD (gestation day) 20, birth weights as well as posh natal survival were generally similar to control values, even in the 1500 ppm exposure group. Postnatal weight gain was also similar to controls early in weaning, but, if maternal exposure was reinitiated, weight gain was reduced in the high exposure group. However, when exposure was continued until delivery, pups in the high exposure group exhibited reduced litter size, birth weight and poor survival. Thus it was likely that the reduction in fetal weight, seen in the developmental toxicity study in mice, was transient and had no postnatal consequences if maternal exposure was terminated at any time prior to delivery.
Trends in Mesothelioma Incidence in Norway 1960-1988
Authors: Mowé Gunnar , Andersen Aage , Osvoll Peter
Published: September 2013

The age and sex related trends in incidence of malignant mesothelioma and trends in notification of mesothelioma to the Labour Inspection between 1960-88 are investigated. For men, the age-adjusted incidence rate increased from 0.4 per 100,000 in the period 1960-69 to 1.4 per 100,000 in the period 1980-88. The number of mesotheliomas notified to the Labour Inspection increased from only 4 in the period 1960-69 to 165 in the period 1980-88. The incidence rate among women was unchanged, about 0.1 per 100,000.
Roentgenographic Manifestations and Pulmonary Function Effects of Asbestos-Induced Pleural Thickening
Authors: Rosenstock Linda
Published: September 2013

Pleural thickening is the most common roentgenographic manifesta tion of past asbestos exposure. In addition to pleural thickening serving as a specific market of exposure, discrete (plaques) and dif fuse pleural fibrosis are important abnormalities because they have been found to be associated with increased risk for other asbestos- related sequelae and to themselves have an adverse effect on pul monary function. We review here the results of an evaluation of a cohort of asbestos-exposed workers, plumbers and pipefitters, who were consecutively enrolled in a large cross-sectional prevalence study. Among the 681 male participants, pleural abnormalities were associated with decreased values of forced vital capacity, an effect independent of ILO profusion grade. The risk for pleural disease was unexplained by smoking status. Diffuse pleural thickening was more common and was associated with greater decrements in func tion than was discrete thickening.
Interspecies Scaling of Anesthetic Potency
Authors: Travis Curtis C. , Bowers John C.
Published: September 2013

Anesthetic potency data for 11 volatile anesthetics were corre lated against body weight in multiple mammalian species, in cluding man. The results indicate that the alveolar concentration necessary to produce anesthesia is approximately constant across species. Because alveolar ventilation rates scale with the 0.75 power of body weight, this implies that administered dose mea sured in mg/kg0.75/day produces the same anesthetic effect in all species. This analysis provides further support for the use of a mg/kg0.75/day interspecies scaling metric for acute toxic effects.
Mortality of 11,500 Nickel Workers—Extended Follow Up and Relationship to Environmental Conditions
Authors: Shannon Harry S. , Walsh Christine , Jadon NI , Julian Jim A. , Weglo John K. , Thornhill Philip G. , Cecutti Albert G.
Published: September 2013

An extended follow-up from 1977-84 was achieved in a cohort of 11,567 nickel workers engaged in mining, milling and smelt ing originally studied from 1950-76. Exposure data were incor porated into the analysis. One nasal cancer occurred. The lung cancer Standardized Mortality Ratio beyond 15 years from first exposure was significantly high overall (128) and in miners (153). However, detailed analyses by era of first mining and du ration of mining, as well as cumulative exposure to different nickel species, did not appear consistent with an occupational etiology since significant trends were not observed. At the levels of exposure incurred, large increases in lung and nasal cancer, observed in nickel refineries elsewhere, did not occur.
Effects of a 13-Week Chloropentafluorobenzene Inhalation Exposure of Fischer 344 Rats and B6C3F1 Mice
Authors: Kinkead Edwin R. , Bunger Susan K. , Kimmel Edgar C. , Flemming Carlyle D. , Wall Henry G. , Grabau John H.
Published: September 2013

Chloropentafluorobenzene (CPFB) has been identified as a can didate simulant for nonpersistent chemical warfare agents. Acute toxicity studies have shown that CPFB has limited adverse ef fects on laboratory animals. A 21-day inhalation study of rats and mice to 2.5, 0.8, and 0.25 mg CPFB/liter resulted in re duced weight gain in male and female rats exposed at the high concentration only and identified the liver as a potential target organ. This multiconcentration inhalation study was designed to detect a no-observable-effect level associated with repeated expo sure to CPFB. Male and female rats and mice were exposed to 250, 50, or 10 mg CPFB/m3 (0.25, 0.05, or 0.01 mg CPFB/li ter) for 13 weeks. No treatment-related effects on body weight, clinical chemistries, mortality, absolute or relative organ weight or histopathology were noted.
Personal Exposure To 25 Volatile Organic Compounds Epa's 1987 Team Study in Los Angeles, California
Authors: Wallace Lance A.
Published: September 2013

The US EPA and the California Air Resources Board studied the exposures of 51 residents of Los Angeles, CA to 25 volatile organic chemicals in air and drinking water in February and July of 1987. Participants carried a personal air monitor consisting of a Tenax cartridge and a small sampling pump for two consecutive 12-hour periods. Concurrently, outdoor air samples were collected in the back yards and indoor air samples were collected in the kitchen and living room. Breath samples were collected at the beginning, middle, and end of the 24-hour monitoring period using a van- mounted spirometer employing Tedlar bags followed by collection on Tenax cartridges. All analyses were by GC/MS. Air exchange measurements were made at all homes using the perfluorotracer method.

For most chemicals, personal air concentrations were greater than indoor air levels, which were in turn greater than outdoor air concentrations. Breath concentrations were more stable than air exposures and were significantly correlated with previous exposure. Using the air exchange measurements, whole-house source strengths were estimated to range between approximately zero for carbon tetrachloride to 10,000 μg/h for para-dichlorobenzene. Ambient concentrations in February were two-three times those in July, perhaps due to strong inversions.
Assessment of Occupational Health Risk From Multiple Exposure: Review of Industrial Solvent Interaction and Implication for Biological Monitoring of Exposure
Authors: Tardif Robert , Goyal Raj , Brodeur Jules
Published: September 2013

This review is a critical survey and evaluation of recent literature on solvent interactions for the assessment of health risk. It addresses the implications of multiple solvent exposures 1) by examining the influence of solvent-solvent and ethanol-solvent interactions on the biological indices of chemical exposure, and 2) by indicating how the eventual modifying effects can be considered in the biological monitoring of mixed exposure. Reviewed studies reveal the effects of toxicokinetic interactions on the biological parameters, and the gaps in our knowledge. The measurement of potentially toxic molecular species is suggested for the biological monitoring of multiple chemical exposure. This approach appears to be important for drawing better quantitative conclusions on the internal exposure to biologically active chemical species. Finally, research needs arising from the critical analysis of the literature are briefly described.
Rapid Hypertensinogenic Effect of Lead: Studies in the Spontaneously Hypertensive Rat
Authors: Nakhoul Farid , Kayne Laurie H. , Brautbar Nachman , Hu Ming-Shu , Mcdonough Alicia , Eggena Peter , Golub Michael S. , Berger Morris , Chang Chwen-Tzuei , Jamgotchian Nora , Lee David B.N.
Published: September 2013

Chronic lead exposure may cause hypertension in normotensive rats. This hypertensinogenic effect has been attributed to perturbations in the renin-angiotensin axis, the contractile resporase of the vascular smooth muscle, or the intracellular Ca2+ homeostasis as a consequence of the inhibition of Na+-K+-ATPase activity. In this study we examined the short-term effect of lead exposure on blood pressure, plasma renin activity, vascular contractility, and renal Na+-K+-ATPase activity and abundance in the spontaneously hypertensive rat. Our data indicate that modest lead exposure caused blood pressure elevation within two weeks in this rat strain that is genetically susceptible to the development of hypertension. This rapid blood pressure-elevating effect did not appear to depend on the mechanisms described in hypertension associated with more chronic lead exposure listed above. This acute model provides an additional approach to the study of lead-induced hypertension.
A Physiologically Based Description of Ethylene Oxide Dosimetry in the Rat
Authors: Krishnan Kannan , Gargas Michael L. , Fennell Timothy R. , Andersen Melvin E.
Published: September 2013

A physiologically based pharmacokinetic (PB-PK) model providing a quantitative description of ethylene oxide (ETO) dosimetry in the rat was developed by integrating information on physiology, tissue solubility of ETO, and rate constants for ETO metabolism and binding. The PB-PK model consisted of nine compartments; liver, lung, testis, brain, fat, venous blood, arterial blood, richly perfused and poorly perfused tissues. The tissue: air partition coefficients of ETO, determined by vial equilibration, were similar among the various tissues (range 44–83). The rate constants for glutathione (GSH) conjugation, hydrolysis, and hemoglobin (Hb)- and DNA- binding were estimated from published data and by conducting in vivo inhalation exposure studies. The model adequately predicted the concentrations of Hb and DNA adducts, hepatic and extrahepatic GSH, and urinary N-acetyl-S-(2-hydroxyethyl)-cysteine following inhalation exposures of 1.2 to 1,200 ppm and intravenous administration of 1 to 100 mg/kg of ETO in male Fischer-344 and Sprague-Dawley rats. There was no evidence of nonlinearity in the overall elimination of ETO in the dose range examined. However, nonlinearities in the components of this first order elimination process (namely GSH conjugation, hydrolysis, exhalation) were found to occur at high exposure concentrations. Characterization of the individual metabolic pathways that affect the tissue dosimetry of ETO is important for interspecies extrapolation and risk assessment for this chemical.
Effect of Lithium Salts on the Microstructure of the Thymus and on Vitamin C Content in Some Lymphatic Organs, the Liver and Suprarenal Glands in F1 Mouse Crosses (CBA X C57BL)
Authors: Ficek Wanda , Lesniewska Jadwiga , Mrowca Dorota
Published: September 2013

The administration of lithium chloride (LiCl) to mice by intraperitoneal injection caused involution in the thymus, both in the cortex and medulla. Lithium also considerably decreased vitamin C (ascorbic acid) content in all of the organs that were studied: thymus, lymph nodes, spleen, suprarenal glands, and liver.
Lys- and Leu-Aminopeptidase Activity after Acute Toluene Exposure in the Rat Brain
Authors: De Gandarias Juan M. , Echevarria Enrique , Irazusta Jon , Casis Ernesto , Casis Luis
Published: September 2013

Changes in Lys- and Leu-aminopeplidase activities in several brain regions of the rat, after acute toluene administration, are described in this research. Aminopeptidase activity has been suggested as a candidate regulator of the degradation of several neuroactive peptides. Lys-aminopeptidase activity was significantly decreased in the thalamus, amygdala, and medulla oblongata. Leu-aminopeptidase activity was significantly decreased in the thalamus and cerebellum. It is suggested that these aminopeptidase activities could play a part in the mechanism of toluene neurotoxicity.
Heavy Metals and the Mammalian Thymus: In Vivo and In Vitro Investigations
Authors: Ficek Wanda
Published: September 2013

This experiment was performed to investigate changes in the thymus of Wistar-strain male rats administered cadmium chloride (CdCl2), mercuric chloride (HgCl2), and lead chloride (PbCl2) salts. The study involved measurement of: 1) deoxyribonucleic acid (DNA) content; 2) ascorbic acid (vitamin C) content; 3) incorporation of 3h-thymidine during in-vitro investigation; and 4) histological and morphological changes.

It was shown in investigations on DNA content that administration of heavy metal salts caused an average 76% decrease in DNA content compared to the control. Moreover, in the thymus of experimental animals, an average 69% decrease in vitamin C content was recorded. In in vitro cultures, heavy metal salts decreased the incorporation of 3H-thymidine in thymic cells.
A Review of the Carcinogenicity of Chemicals Most Frequently Found at National Priorities List Sites
Authors: Faroon Obaid M. , Williams Malcolm , O'Connor Ralph
Published: September 2013

Several studies have shown that numerous National Priorities List (NPL) sites have been contaminated with arsenic (747), cadmium (791), chloroform (596), or nickel (664). The National Toxicology Program (NTP, 1991) has classified these substances as known human carcinogens (arsenic and certain arsenic compounds) or as substances that may reasonably be anticipated to be carcinogens (cadmium and certain cadmium compounds, chloroform, and nickel and certain nickel compounds). The general population is probably exposed to low levels of these hazardous substances through drinking water, eating food, or inhaling contaminated air. People working or living near industries and facilities that manufacture and use chloroform, nickel, arsenic, or cadmium may be exposed to higher than background levels of these hazardous substances. Multiple pathways of exposure may exist for populations near hazardous waste sites. For example, high levels of chloroform (1,890 ppb) were found in well water near a waste site; high levels of cadmium exposure may exist for individuals living near cadmium-contaminated waste sites.
Liquid/Air Partition Coefficients of the Trimethylbenzenes
Authors: Järnberg Jill , Johanson Gunnar
Published: September 2013

Liquidlair partition coefficients (λ) of the three isomers of trimethylbenzene (1,2,3-, 1,2,4-, and 1,3,5-TMB) were determined in vitro using automated head space gas chromatography. The liquids used were water (physiological saline), fresh human blood, and olive oil. The λwater/air were 1.23 (95% confidence interval 1.11-1.35 ) for 1,3,5-TMB, 1.61 (1.47-1.75) for 1,2,4-TMB, and 2.73 (2.54-2.92) for 1,2,3-TMB. Corresponding λ blood/air were 43.0 (40.8-45.2), 59.1 (56.9-61.3), and 66.5 (63.7-69.3). As expected, the TMBs have a high affinity for olive oil, the λoil/air being 9,880 (9,620-10,140), 10, 200 (9,900-10,400), and 10,900 (10,500-11,300), respectively. It is notable that all partition coefficients increase in the order 1,3,5-TMB < 1,2,4-TMB < 1,2,3-TMB.