bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview of Structure-Activity Relationships as an Alternative To Testing in Animals for Carcinogenicity, Mutagenicity, Dermal and Eye Irritation, and Acute Oral Toxicity
Authors: Enslein Kurt
Published: September 2013

The use of structure-activity relationships (SAR) has proven practical for the development of equations which can be used to estimate the above-listed endpoints for a large variety of chemicals. The SAR models predict these endpoints correctly in 85 to 97% of the cases and often surpass in their predictive ability the results obtainable from the equivalent biological assays.

These SAR models are being used at several levels: drug, or more generally, chemical discovery; prioritization for testing; regulatory affairs; investigation of detoxification mechanisms; and risk estimation.

In the new compound (discovery) use, potential toxic effects of a set of related compounds are investigated before synthesis to select those chemicals with the lesser probabilities of producing toxic effects for further investigation, at considerable savings in research expenditure since fewer compounds need to be synthesized, and the avoidance of blind alleys. Prioritization for testing is used in numerous instances, such as selecting those chemicals in an environment which are most likely to have toxic effects for priority attention. SAR models are used by regulatory agencies to determine the possible toxic effects of chemicals for which data insufficient to render decisions have been submitted, and to gain insight into possible toxicity problems. SAR models are also used to investigate possible metabolites, and toxicity mechanisms due to the ability of making computer-based structural modifications and observing the effects on the modelled toxic endpoints. Risk analysis is a natural outgrowth of several of the above applications, and is particularly useful for SAR models of carcinogenicity.

SAR models as alternatives to animal bioassays should be used in the context of other information for the chemicals of concern. Just as bioassays and in vitro methods have their limitations, so do SAR models. These include the sometimes limited data base on which to base an SAR model, the temptation to extrapolate beyond the confines of the model, and the noise inherent in the bioassays on which the models are based. Within these constraints SAR models have a considerable potential in reducing the number of animals used in toxicity testing.
In Situ Assessment of Genotoxic Hazards of Environmental Pollution
Authors: Sandhu Shahbeg S. , Lower W.R.
Published: September 2013

The potential impact of the environmental pollutants on human health can be evaluated by the laboratory analysis of the environmental samples or by the measurement of the biological effects on indigenous populations and/or specific test organisms placed in the environment to be monitored. A canary in a cage, used by 19th century miners as a biological indicator for rising levels of toxic gases, is a classical example of in situ hazard identification. The induced toxic effects are often the result of synergistic and antagonistic interactions among various physical and chemical factors that are difficult to reproduce in the laboratory. Therefore, conceivably the biological effects measured on or near the impacted site have greater relevancy for hazard assessment to man than from the data derived from the environmental samples analyzed in the lab. The organisms most commonly employed for the assessment of mutagenicity under real-world conditions are: (1) flowering plants, (2) wild and captive mammals, and (3) aquatic vertebrates. Plant species such as Tradescantia paludosa, Zea mays, and Osmunda regalis have been used for monitoring ambient air quality around several major industrial cities in the U.S.A., nuclear power plants, and industrial waste sites, and also for the assessment of potential health effects of municipal sewage sludges. Domestic animals such as dogs can be used as sentinels to provide information on the effects of contaminants in the environment and have been used to a limited extent to evaluate the environmental influences on the occurrence of breast cancer and osteosarcoma. Cytogenetic analysis from feral and wild animals has been employed for assessing the health hazards and prioritizing the clean-up efforts at hazardous waste sites. Aquatic animals have been used more often than terrestrial animals or plants to identify and characterize the genotoxic effects of environmental pollution. Since 1970, a number of studies has been reported on the mutagenic and neoplastic effects on aquatic animals from coastal areas and continental rivers, lakes, and ponds. The limitations of in situ environmental assessment are lack of control over the physical environmental components, inherent variability and interactions of test organisms, lack of control of exposure doses, and difficulty of finding concurrent experimental controls. Nevertheless, flowering plants, terrestrial, and aquatic animals may serve as useful sentinels and biomarkers of environmental pollution.
In Vitro Screens From Cns, Liver and Kidney for Systemic Toxicity
Authors: Tyson Charles A. , Stacey Neill H.
Published: September 2013

The development and evaluation of in vitro systems from target organs for preliminary assessments of the potential for systemic toxic effects has been receiving increased attention. This review presents a synopsis of progress made in developing toxicity screens for three common target organs and identifies further work needed for more complete validation.
The Further Development of a Mammalian DNA Alkaline Unwinding Bioassay With Potential Application to Hazard Identification for Contaminants from Environmental Samples
Authors: Daniel F. Bernard , Chang Lina W. , Schenck Kathleen M. , Deangelo Anthony B. , Skelly Michael F.
Published: September 2013

Recently, we have detailed a DNA alkaline unwinding assay (DA UA) that can be used to rapidly measure chemically induced strand breaks in mammalian cells (Daniel et al., 1985). In this paper we present further development of this assay, including: (1) studies on the relationship between DNA adducts and DNA strand breaks; (2) evaluation of the role of cytotoxicity in DNA strand breaks; and (3) application of the DA UA to cell preparations from the liver of mice dosed with methylating agents. The level of DNA adducts produced in human CCRF-CEM cells by treatment with benzo(a)pyrene diol-epoxide (BPDE), N-acetoxy-2-acetyl amino fluorene (AAAF), and various methylating agents was linear with concentration over several orders of magnitude. Likewise, the level of strand breaks increased with the concentration over the same dose range. The strand breaks/adduct ratio ranged from 0.05 for the methyl adducts to 0.001 for the BPDE adducts. Using these values and the inherent sensitivity of the DA UA (circa 100 to 1000 breaks/ cell), (Daniel et al., 1985), the ability of the assay to detect DNA damage induced by various classes of chemical carcinogens can be calculated.

The DA UA appears to be useful for assessing the relative potency of various environmental genotoxic effects on mammalian cells. In addition, it can be conducted on cells isolated from target organs of whole animals.
Risk Assessment Initiatives for Noncancer Endpoints: Implications for Risk Characterization of Chemical Mixtures
Authors: Derosa C.T. , Dourson M.L. , Osborne R.
Published: September 2013

Current methods employed in risk assessment for noncarcinogens are associated with the estimation of reference doses (RfDs). These strategies reflect (appropriately) a protective philosophy in both theory and practice. The approaches are limited, however, in terms of the ability to project the likelihood of specific hazard above the reference dose and to integrate the health hazards of exposure to chemical mixtures (including both cancer and noncancer endpoints).

Ongoing efforts that address guidelines for risk assessment of non carcinogens, both singly and as components of mixtures, are pres ented. Included is a description of the range of potential biological response categories and associated parallel issues of adversity and severity. For example, the progression of histopathological change, organ system dysfunction and organismal disability is examined as it may affect risk characterization of mixtures. Mechanistic princi ples are suggested as an appropriate focus to systematically evalu ate this progression. Once established, these principles may provide a reasonable framework in which to more accurately characterize risks associated with chemical mixtures.
Pulmonary Function, Airway Responsiveness, and Respiratory Symptoms in Asthmatics Following Exercise in No2
Authors: Roger L. Jack , Horstman Donald H. , Mcdonnell William , Kehrl Howard , Ives Philip J. , Seal Elston , Chapman Robert , Massaro Edward
Published: September 2013

Two experiments were conducted to determine respiratory responses of persons with asthma performing intermittent moderate exercise while exposed to low concentrations of NO2. In the first, preliminary experiment, 13 male subjects, aged 19–35, with mild asthma were exposed on separate days in a chamber (natural breathing, 20°C, 40% RH) to 0.30 ppm NO2 and to a control or “clean air” exposure (0.0 ppm NO2). Exposure included three 10–min periods of moderate treadmill exercise (VE = 44.5 liter/min), each followed by symptom measurement and pulmonary function testing. The average decrease in FEV1 following the initial 10 min exercise in 0.30 ppm was 11% which was significantly greater (p < 0.05) than that observed in clean air (7%). Differences in FVC and SRaw were not significantly different at this time. Slight cough and dry mouth and throat were apparent only after the first exercise in NO2. After the second and third exercises, decreases in FEV1 and FVC and increases in SRaw were significantly greater in 0.30 than in 0.0 ppm NO2. Individual subject responses were variable. These results suggested that some asthmatics who perform moderate exercise while exposed to 0.30 ppm NO2 may experience bronchoconstriction and reduction in spirometric performance.

Because of these preliminary findings, a more comprehensive, concentration-response experiment was conducted. Twenty-one male volunteers with mild asthma were exposed for 75 min with natural breathing to 0.0, 0.15, 0.30, and 0.60 ppm NO2. Exposure included three 10–min periods of moderate treadmill exercise (VE = 43 liter/min), each exercise followed by symptoms measurement and pulmonary function testing. In addition, airway responsiveness was measured two hr after each exposure by methacholine bronchial challenge testing. In the control exposures (0.0 ppm NO2), the exercise alone caused substantial decrements in pulmonary function. These decrements (as measured by decreases in FEV1 and FVC, and increases in SRaw) were not increased relative to the control exposure after any exercise session in any concentration of NO2. Furthermore, there was no overall group-averaged indication of a concentration-related effect of the NO2 on pulmonary function. Likewise, symptoms reported after NO2 exposure were not significantly different from those reported in clean air. Group-averaged airway responsiveness after exercise in NO2 was also not different from responsiveness after exercise in clean air. For only two subjects was there any indication of a concentration-related increase in airway responsiveness due to exposure to NO2. The findings of no effects in this larger concentration-response study do not support the findings of single-concentration studies by us and others. Possible explanations are differences in subject sampling, variability in subjects' responses, or other factors such as seasonal variation in response.
Mesotheliomas Following Exposure to Asbestos Used in Railroads: the Italian Cases
Authors: Maltoni Cesare , Pinto Carmine , Mobiglia Alberto
Published: September 2013

The available knowledge on the oncogenic risks of asbestos, the data on the uses of asbestos in railroads, with particular regard to the Italian State Railroads (Ferrovie dello Stato=FS), and the groups at risk due to the exposure to asbestos used in railroads were briefly reviewed.

The available data on the pathological effects of such exposure, and in particular on the onset of mesotheliomas among machinists and other railroad workers, were also summarized.

Eighty-five cases of mesothelioma (80 pleural, 4 peritoneal, and 1 pericardial), related to the exposure to asbestos used in railroads, observed in various Italian regions, were then reported. Twenty- eight of these cases (among which 27 reported in the Emilia- Romagna Region) were submitted to a detailed study at the Bologna Institute of Oncology. Fifty cases of mesothelioma occurred among FS workers, in particular machinists; 30 cases occurred among machinists of rolling-stock workshops not belonging to the FS; 3 cases occurred among travelling workers of rolling-stock not belonging to the FS; and 2 cases were found in family members (a daughter and a wife) of FS workers. This series of cases, together with similar data from the literature, proves the existence of an actually health risk due to asbestos used in railroads, and indicates its gravity.

On the basis of the available data, the following steps are consid ered necessary: the adoption of preventive measures, the perfor mance of medical oncological surveillance, the promotion of systematic epidemiological investigations, and, finally, more em phasis on basic research, aimed at generating information on the biological events taking place during the incubation period of the tumors, to be used for reducing the effect of exposure, and there fore for contrasting the onset of the disease in those who, having been exposed, although healthy, are potentially at high risk.
Benzo-a-Pyrene: Environmental Partitioning and Human Exposure
Authors: Hattemer-Frey Holly A. , Travis Curtis C.
Published: September 2013

A multimedia transport model was used to evaluate the environ mental partitioning of benzo-a-pyrene ( BaP) . Measured and pre dicted environmental concentrations were used to estimate the accumulation of BaP in the food chain and the subsequent ex tent of human exposure from inhalation and ingestion. Results show that BaP partitions mainly into soil ( 82%) and sediment ( 17%) and that the food chain is the dominant pathway of hu man exposure, accounting for about 97% of the total daily in take of BaP. Inhalation and consumption of contaminated water are only minor pathways of human exposure. The long-term av erage daily intake of BaP by the general population of the U. S. is estimated to be 2.2 micrograms (μ g) per day. Cigarette smok ing and indoor activities do not substantially increase human ex posure to BaP relative to exposures to background levels of BaP present in the environment. Since the increased lifetime risk as sociated with human exposure to background levels of BaP is 3.5 x 10-4, we conclude that ingestion of food items contami nated with BaP may pose a serious health threat to the U. S. population.
Dangerous and Cancer-Causing Properties of Products and Chemicals in the Oil Refining and Petrochemical Industry: Part I Carcinogenicity of Motor Fuels: Gasoline
Authors: Mehlman Myron A.
Published: September 2013

Studies in humans and animals have shown that gasoline contains a number of cancer- causing and toxic chemicals such as 1,3-butadiene, benzene, toluene, ethylbenzene, xylenes, isoparaffins, methyltert-butylether, and others. The International Agency for Research on Cancer (IARC) in its Monograph Supplement 7 (1987) concludes that "in the absence of adequate data on humans, it is biologically plausible and prudent to re gard agents for which there is sufficient evidence of carcinogenicity in experimental animals as if they present a carcinogenic risk to humans." Epidemiological studies in humans provide important evidence of potential increased risk of leukemia, lymphatic tissue cancers, cancers of the brain, liver, and other organs and tissues. Recently (July, 1990) the American Conference of Governmental Industrial Hygiene (ACGIH) recom mended that the TLV-TWA for benzene be reduced from 1 ppm to 0.1 ppm (ACGIH, 1990). The Collegium Ramazzini and others have also recommended that the exposure level for 1,3-Butadiene be reduced from 1,000 ppm to below 0.2 ppm. This recom mendation is based on the findings that were presented at the Symposium on Toxicol ogy, Carcinogenesis, and Human Health Aspects of 1,3-Butadiene (Environ. Health Perspec., 1990). Thus, studies on health effects resulting from very low levels of ben zene, 1,3-butadiene, and other cancer-causing chemicals—components of gasoline— necessitate that all avoidable exposure to gasoline or gasoline vapors be avoided.
Chlorine Gas Exposure and the Lung: A Review
Authors: Das Rupali , Blanc Paul D.
Published: September 2013

We conducted a review of the literature detailing the respiratory effects of chlorine, an extremely important but toxic halogen. Historically, the heaviest mass inhalational exposures to chlorine resulted from World War I gassing. Currently potential human exposure to chlorine inhalation occurs in a variety of settings in the workplace, as a result of inadvertent environmental releases, and even in the home due to household cleaning mishaps. Chlorine species are highly reactive; tissue injury results from exposure to chlorine, hydrochloric acid, hypochlorous acid, or chloramines. Acute, high level exposure to chlorine gas in occupational or environmental settings results in a variety of dose-related lung effects ranging from respiratory mucus membrane irritation to pulmonary edema. Pulmonary function testing can reveal either obstructive or restrictive deficits immediately following exposure, with resolution over time in the majority of cases. However, some of those exposed may demonstrate long-term persistent obstructive or restrictive pulmonary deficits or increased nonspecific airway reactivity after high level exposure to chlorine gas. Symptoms and signs following inhalation of mixtures of chlorine-containing cleaners in the home are similar to those after occupational exposures and environmental releases. Although generally less severe, these events may be extremely common. Controlled human exposure data suggest that some subjects may be more responsive to the effects of chlorine gas; epidemiologic data also indicate that certain subpopulations (e.g., smokers) may be at greater risk of adverse outcome after chlorine inhalation. Although these findings are intriguing, additional study is needed to belter delineate the risk factors that predispose toward the development of long-term pulmonary sequelae following chlorine gas exposure.
Liver Function in Rats Treated Individually and with a Combination of Xylene, Toluene and Methanol
Authors: Rana Suresh V.S. , Kumar Sunil
Published: September 2013

The individual and combined influences of three industrial solvents (namely xylene, toluene, and methanol) on certain parameters of liver function in laboratory rats have been studied. Although individual treatments with all three solvents elevated activities of serum enzymes (i.e., GOT, GTP, and alkaline phosphatase), and did manifest hyperbilirubinemia, nevertheless metabolic interaction occurring after their combined treatment suggested a weak antagonistic mechanism. This assumption has been supported by the fact that the detoxification ability of the liver, as indicated by the formation of hippuric acid, improved after the combined treatment.
Occupational Skin Hazards from Synthetic Plastics
Authors: Tosti Antonella , Guerra Liliana , Vincenzi Colombina , Peluso Anna Maria
Published: September 2013

Epoxy and acrylic resins have numerous industrial applications but are also widely used in the household environment. These compounds are presently one of the most important sources of occupational contact dermatitis.

Contact sensitization to epoxy resins is usually caused by the resin itself but hardeners or other additives, such as reactive diluents, plasticizers, fillers and pigments, can occasionally be responsible. Since completely cured epoxy resins are not sensitizers, epoxy resin sensitization is always due to the presence, in the final polymer, of uncured allergenic low molecular weight oligomers.

Acrylates are now considered the fourth most common cause of contact sensitization due to resins. Unpolymerized monomers of acrylic compounds are known to be responsible for the contact allergy. Accelerators, inhibitors and catalysts, which are usually added to the acrylates to promote the polymerization process, can also sensitize.

Both allergic and irritant contact dermatitis may be caused by exposure to epoxy or acrylic resins and their additives. Contact urticaria, allergic or irritant airborne contact dermatitis caused by volatile compounds, onychia and paronychia can also occur.

From January of 1984 to May of 1992 we detected 39 cases of occupational allergic contact dermatitis to epoxy resin system substances and 11 cases of occupational contact sensitization to acrylic compounds.

In our experience, the electronics industry as well as paint and glue related activities were the most important sources of epoxy sensitization. Dental materials and anaerobic sealants were found to be the most frequent acrylate sensitizers.
Possible Role of Free Radical Intermediates in Hepatotoxicity of Hydrazine Derivatives
Authors: Albano Emanuele , Goria-Gatti Lucia , Clot Paolo , Jannone Anna , Tomasi Aldo
Published: September 2013

Hydrazine derivatives constitute a wide group of compounds and have found application in industry, agriculture, and (as therapeutical agents) medicine. In spite of their widely spread use, several hydrazine derivatives arc known to exert hepatotoxic effects and are carcinogenic.

Free radical species are produced during the hepatic biotransformation ofalkylhydrazines by both rat and humans liver microsomes. Cytochrome P-450 dependent monoxygenase system is responsible for the production of these reactive species and specific cytochrome P-450 isoenzymes appear to catalyze the formation of free radical intermediates.

Free radicals generated during the metabolism of alkylhydrazines are capable of inducing oxidative stress in isolated hepatocytes and might contribute to the development of cell injury.
Norplant: Systemic Immunological Complications — Case Report
Authors: Campbell Andrew , Brautbar Nachman
Published: September 2013

The Norplant* system is composed of a set of six Silastic* (silicone polydimethysiloxane) capsules measuring 34 mm by 2.4 mm, each containing 36 mg of levonorgestrel and sealed at either end with a medical grade silicone elastomer adhesive. Levonorgestrel is a synthetic progestin, widely used in combination oral contraceptives and in single-agent "mini-pills. " In a procedure completed in less than 15 minutes by an experienced physician, the six capsules are surgically implanted subdermally, most commonly on the inside of the left upper arm. The levonorgestrel diffuses through the Silastic material into the blood stream and is carried to the target organs. Ovulation is suppressed in the majority of the cycles during the first years of use, and cervical mucus is thickened, inhibiting sperm penetration. During use, the effective delivery of levonorgestrel is about 30 mcglday from day 500 to day 2300. Recently, we have seen patients with complications from Norplant, and we describe here a patient who presented with systemic complications resulting from both the endocrinological aspects of Norplant and the immunological aspects of the Silastic implants.

To our knowledge this is the first case report in the western medical literature describing systemic immunological complications as a result of a failed Norplant device.
Methods of Assessing Dermal Absorption With Emphasis On Uptake From Contaminated Vegetation
Authors: Durkin P.R. , Rubin L. , Withey J. , Meylan W.
Published: September 2013

Dermal absorption may be an important route of exposure in several exposure scenarios for workers and the general public. Because criteria (e.g., RfDs or MRLs) for chemical exposures are usually expressed in units of mg/kg/day, risk assessments often attempt to convert dermal exposure data to units of mg/kg/day absorbed dose. For some types of dermal exposure involving direct and continuous contact with liquids, Fick's first law may be used. In other cases, such as those involving spills onto the skin surface or dermal exposure to contaminated vegetation, the applicability of Fick's first law is limited.

This analysis focuses on a method for estimating absorbed dose from dermal contact with contaminated vegetation or other surfaces. The method involves two steps: estimating the transfer rate from contaminated vegetation to the skin surface, and estimating the extent of absorption from the skin surface into the body.

A generic equation can be derived for estimating the transfer rate (TR) from dislodgeable foliar residues (DFR):

logTR = 1. 09 logDFR + 0. 05.

Given the surface area of the exposed skin and the duration of contact, this equation can be used to estimate the amount of a chemical deposited on the surface of the skin. This equation is based on data from eight different studies using 16 different pesticides. Excluding one outlier (Vinclozolin), the squared correlation coefficient for this equation is 0.78, and the model is significant at p < 0. 00001.

Data from a series of studies by Feldmann and Maibach (1969, 1970, 1974) are used to estimate dermal absorption. These studies were selected as the most relevant for risk assessment because most of the experimental subjects are human and because the nature of the dermal exposures was closely related to many exposure scenarios used in risk assessments. For all 47 compounds included in this series of studies, there were no significant correlations between commonly available physical or chemical properties and dermal absorption. For those compounds with a Ko/w > 1.85, however, the average daily absorption rate (AR) over a five-day postexposure period can be estimated from the molecular weight:

logAR = -0.04MW + 1.5.

The squared correlation coefficient for this equation is 0.68, and the model is significant at p < 0.00001.

The usefulness of this approach is evaluated using a study by Harris and Solomon (1992) in which the absorption of 2,4-D from contaminated turf was measured in a group of volunteers. The estimated absorbed dose using the equations above is very close to the measured values.
Hydrogen Sulfide and Reduced-Sulfur Gases Adversely Affect Neurophysiological Functions
Authors: Kilburn Kaye H. , Warshaw Raphael H.
Published: September 2013

Hydrogen sulfide (H2S) above 50 parts per million (ppm) causes unconsciousness and death. Lower doses of H2S and related gases have been regarded as innocuous, but the effects of prolonged exposure have not been studied. This study was designed to determine whether people exposed to sulfide gases as a result of working at or living downwind from the processing of "sour" crude oil demonstrate persistent neurobehavioral dysfunction. Thirteen former workers and 22 neighbors of a refinery complained of headaches, nausea, vomiting, depression, personality changes, nosebleeds, and breathing difficulties. Their neurobehavioral functions and a profile of mood states (POMS) were compared to 32 controls, matched for age and educational level. The exposed subjects' mean values were statistically significantly abnormal compared to controls for two-choice reaction time, balance (as speed of sway), color discrimination, digit symbol, trail-making A and B, and immediate recall of a story. Their POMS scores were much higher than those of controls. Visual recall was significantly impaired in neighbors, but not in exworkers.

It was concluded that neurophysiological abnormalities were associated with exposure to reduced sulfur gases, including H2S from crude oil desulfurization.
General Toxicity and Reproductive Screen of Liquid Propellant Xm46 Administered in the Drinking Water of Sprague-Dawley Rats
Authors: Kinkead E.R. , Wolfe R.E. , Salins S.A. , Flemming C.D. , Leahy H.F. , Caldwell D.J. , Miller C.R. , Marit G.B.
Published: September 2013

Liquid propellant XM46 is being considered as a replacement for solid propellants, both as part of a regenerative injection gun system and as a working fluid in an electrothermal gun system. The XM46 formulation contains hydroxylammonium nitrate, triethanolammonium nitrate, and water. Male and female Sprague-Dawley rats received XM46 in drinking water containing 2.0, 1.0, 0.2, or 0.0 g XM46/liter throughout a 90-day study. Mating occurred following 14 days of treatment. One-half the male rats per group were necropsied after 28 days of treatment; the remaining males and all dams were necropsied following 90 days of treatment. No mortality occurred in any of the parental animals during the study. The study did not demonstrate any adverse effects on reproduction or litter parameters. Hemolytic anemia and methemoglobinemia were common in both sexes of rats. Splenomegaly was found in both sexes; in male rats as early as 28 days. Exposures via drinking water containing XM46 for 90 days did not result in any decrease in reproductive performance in male or female rats, but it did result in clinical signs of hemolytic anemia at doses as low as 17 mg/kg/day.
Respiratory Peripheral Sensory Irritation and Hypersensitivity Studies With Glutaraldehyde Vapor
Authors: Werley Michael S. , Burleigh-Flayer Heather D. , Ballantyne Bryan
Published: September 2013

Overexposure to glutaraldehyde (GA) vapor (CAS No. 111-30-8) is known to cause peripheral sensory irritant effects in humans. Respiratory sensory irritation was investigated in male ND4 Swiss Webster mice to quantify the effect, and also as a preliminary to a study of the respiratory sensitizing potential of GA. For the irritation study, groups of four mice were exposed to seven different GA vapor concentrations in the range of 1.6 to 36.7 ppm, while respiratory rate (RR) was measured by plethysmography. Concentration-related decreases in RR were measured, with a maximum decrease at 3 to 20 min, which was sustained, indicating an absence of desensitization. The 50% decrease in RR (RD50) was calculated to be 13.9 ppm, which accords with the known sensory irritancy of GA and other aliphatic aldehydes. In a separate study, the respiratory sensitizing potential of GA vapor was studied in male Hartley guinea pigs, who were exposed for one hour per day for five consecutive days to an inducing GA vapor concentration of 13.9 ppm. Subsequent challenge exposures to 4.4 ppm at 14, 21, and 35 days after the final induction exposure did not produce any evidence of respiratory sensitization. The above findings confirm that GA vapor is a moderately potent peripheral sensory irritant, and does not produce respiratory sensitization in the guinea pig at the concentrations tested.
Dose- (and Time-) Dependent Blockade of Pregnancy in Sprague-Dawley Rats Administered Ammonium Dinitramide in Drinking Water
Authors: Kinkead Edwin R. , Wolfe Robin E. , Feldmann Marcia L.
Published: September 2013

Ammonium dinitramide (ADN) is a class 1.1 explosive oxidizer that can be used in solid rocket propellant mixtures and explosives. A 90-day general toxicity/ reproductive screen performed on this compound at doses of 162, 103, 29, and 0.0 mg ADNlkglday resulted in a treatment-related adverse effect on litter production. Incidences of animals producing litters (1/11, 3/12, 12/12, and 11/12, respectively) and mean numbers of pups per litter (7, 7, 16, and 15, respectively) both were statistically significantly less than controls. In a follow- up study, mated dams treated with ADN at the same doses and examined at gestation days (GDs) 10 and 20 showed an effect in fetus loss similar to that seen in the reproductive screen. A pre- versus postimplantation dosing regimen indicated that implantation is vulnerable to ADN effects during the preimplantation period (GDs 1-3). No implantation sites were found in the rats treated with 2000 mg ADN/L drinking water (target dose of 160 mg ADNlkglday) during GDs 1-3. Numbers of implantation sites found in the rats treated during GDs 4-8 were similar to those found in the control group. The pituitary was not identified specifically in this study as the site of primary action, but serum progesterone was reduced by 27%, which may have resulted in reduced fertility.
The New York Angler Cohort Study: Exposure Characterization and Reproductive and Developmental Health
Authors: Vena John E. , Buck Germaine M. , Kostyniak Paul , Mendola Pauline , Fitzgerald Edward , Sever Lowell , Freudenheim JO , Greizerstein Hebe , Zielezny Maria , McReynolds James , Olson James
Published: September 2013

The New York State Angler Study will evaluate the association between past and current consumption of contaminated fish from Lake Ontario and both short- and long-term health effects in a population-based cohort. It will measure fish consumption and reproductive and developmental health among 10,518 male anglers and 6,651 of their wives or partners, as well as among 913 female anglers. To characterize exposure among subgroups of the cohort, further analytical methods were developed and implemented to measure specific polychlorinated biphenyls (PCB) congeners, methylmercury, and other substances in biological samples. Exposure assessment has been completed for a stratified random sample of 321 anglers. In addition, analyses for 79 congeners of PCBs are complete for 177 anglers. A special study of duck andturtle consumers currently is underway. Telephone interviews have been completed with 2,454 of the 2,999 women who planned a pregnancy between 1991 and 1994. The entire cohort of male anglers, partners of male anglers, and female anglers has been submitted for matching with the New York State live birth and fetal death registries to obtain lifetime reproductive histories. A medical record abstraction study will assess perinatal and developmental outcomes among the 3,442 births that occurred between 1986 and 1991. Finally, a study of breast milk from currently lactating women is underway, and 215 breast milk samples have been collected from the planned pregnancy subcohort. Progress on each of the study components is discussed herein.
Dose-Response in Perinatal Exposure To Polychlorinated Biphenyls (PCBs): the Michigan and North Carolina Cohort Studies
Authors: Jacobson Joseph L. , Jacobson Sandra W.
Published: September 2013

Two prospective, longitudinal studies—one in North Carolina and one in Michigan—have examined effects of prenatal polychlorinated biphenyl (PCB) exposure on behavioral and cognitive development in infants and children. The Michigan cohort was selected to overrepresent the offspring of women who had eaten relatively large quantities of Lake Michigan fish; the North Carolina cohort was drawn from the general population. Both studies collected umbilical cord serum and maternal serum and milk samples. In both studies, the children were assessed at birth, during infancy, and during the preschool period, and multivariate statistical analysis was used to control for confounding. When exposure was assessed in terms of maternal body burden, effects were seen only in the most heavily exposed children: the top 3-5% of the general population North Carolina sample and the top 11% of the fisheater sample in Michigan.
Red Blood Cell Glycerol Lysis and Hematologic Effects in Occupational Benzene Exposure
Authors: Bogadi-Are Ana , Turk Rajka , Karacic Visnja , Zavalic Marija , Trutin-Ostovic Karmen
Published: September 2013

Forty-nine female workers in the shoemaking industry, exposed to a solvent mixture containing benzene and twenty-seven non-exposed controls, were investigated. Concentrations of benzene and toluene in the working atmosphere, as well as benzene and toluene in blood and phenols in pre- and post-shift urine as parameters of biological monitoring, were determined. In order to assess hematotoxic risk, a complete blood cell count with differential, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, reticulocytes, serum iron, alkaline phosphatase in neutrophils and red blood cell glycerol lysis time were determined in all subjects.

Benzene concentrations in the workplace atmosphere at the shoemaking factory ranged from 1.9 to 14.8 ppm (median=5.9). Significant difference in benzene in blood (p = 0.005) and phenol in post-shift urine (p = 0.003) between exposed workers and controls confirmed exposure to benzene. Hemoglobin level (p = 0.02) and mean corpuscular hemoglobin concentration (p = 0.0002) in the shoe workers were lower, and band neutrophils (p = 0.005) and mean corpuscular volume (p = 0.03) higher, than in controls. Red blood cell glycerol lysis time was significantly higher (p = 0.000001) in shoe workers (X ± SD = 41.6 ± 8.9) than in controls (X ± SD = 31.1 ± 6.5) and showed a significant correlation with exposure biomarkers.

The results confirm that benzene exposure below 15 ppm may produce qualitative abnormalities, particularly macroerythrocytosis and increased red cell glycerol resistance, in the absence of an overt quantitative decrease in circulating blood cells. Increased resistance to the hemolytic action of glycerol is a potentially useful biological monitoring procedure in medical surveillance of benzene exposed workers. The results of this study suggest that potential threshold concentration for hematologic effects of benzene is lower than 15 ppm.
Reproductive and Thyroid Hormone Levels in Rats Following 90-Day Dietary Exposure To Pcb 28 (2,4,4'-Trichlorobiphenyl) or Pcb 77 (3,3',4,4'-Tetrachlorobiphenyl)
Authors: Desaulniers Daniel , Poon Raymond , Phan Wendy , Leingartner Karen , Foster Warren G. , Chu IH
Published: September 2013

Subchronic exposure to the PCB congener 77 (PCB 77) and 28 (PCB 28) was previously shown to induce histological changes in the thyroid and in the brain biogenic amines levels, suggesting possible effects on thyroid and reproductive hormone levels. Thus, the effects of a 90-day dietary exposure to PCB 28 or 77 on luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations were studied in male rats, as well as the levels of thyroid-stimulating hormone, thyroxine (T4) and uridine diphosphate-glucuronyl transferase (UDP-GT) activity in both genders. Weanling Sprague Dawley rats were randomly distributed into groups of 10 rats and were fed, for the next 13 weeks, purina lab chow containing 50, 500, 5000, or 50 000 ppb of PCB 28 or 10, 100, 1000, or 10 000 ppb of PCB 77. The serum concentrations of T4 were decreased in rats of both sexes receiving 1000 ppb or more of PCB 77, and was associated with an increased activity of UDP-GT which reached significance only in the females. There was a tendency for the highest dose of PCB 28 also to decrease serum T4 concentrations in the female rats. None of the PCB treatments significantly altered gonadotropin, TSH, or testosterone concentrations. These results suggest that thyroid functions may be more susceptible or adapt less readily than the pituitary gland and the testes to endocrine disruption caused by PCB congeners.
Environmental Neurotoxic Effects: the Search for New Protocols in Functional Teratology
Authors: Colborn Theo , Smolen Michael J. , Rolland Rosalind
Published: September 2013

Large quantities of a number of man-made chemicals with the potential to disrupt the developing endocrine and nervous systems in wildlife and humans have been released into the environment. These chemicals are particularly damaging during the embryonic, fetal, and early postnatal periods because they resemble or interfere with the hormones, neurotransmitters, growth factors, and other signaling substances that normally control development. The effects are in many cases irreversible and often are expressed as changes in function rather than as obvious birth defects or clinical diseases. Functional changes pose challenges in documenting the extent of the lesion, especially in the case of neuroendocrinological damage. In the past decade, researchers have added new dimensions to their research strategies in order to compensate for these difficulties. The new approaches reveal more about the extent of the distribution of and exposure to chemicals that interfere with the endocrine and nervous systems and strengthen the links between exposure and damage in developing wildlife and humans. Based on this new knowledge, opportunities abound for extensive multi-disciplinary research involving developmental neurotoxicity.
Neurobehavioral Alteration in Rodents Following Developmental Exposure To Aluminum
Authors: Alleva Enrico , Rankin Judith , Santucci Daniela
Published: September 2013

Aluminum (Al) is one of the most abundant metals in the earth's crust, and humans can be exposed to it from several sources. It is present in food, water, pharmaceutical compounds, and in the environment, e.g., as a result of acid rain leaching it from the soil. Exposure to Al has recently been implicated in a number of human pathologies, but it has not yet been definitely proved that it plays a major causal role in any of them. In this paper we review the effects of developmental exposure of laboratory animals to Al salts as a model for human pathological conditions. The data presented show behavioral and neurochemical changes in the offspring of AL-exposed mouse dams during gestation, which include alterations in the pattern of ultrasonic vocalizations and a marked reduction in central nervous system (CNS) choline acetyltransferase activity. Prenatal Al also affects CNS cholinergic functions under Nerve Growth Factor (NGF) control, as shown by increased central NGF levels and impaired performances in a maze learning task in young-adult mice. The need for more detailed studies to evaluate the risks for humans associated with developmental exposure to Al, as well as the importance of using more than one strain of laboratory animal in the experimental design, is emphasized.
The National Exposure Registry: Analyses of Health Outcomes From the Benzene Subregistry
Authors: Burg Jeanne R. , Gist Ginger L.
Published: September 2013

The purpose of the National Exposure Registry is to assess the long-term health consequences to a general population from long-term, low-level exposures to specific substances in the environment. This study investigates the health outcomes of 1, 143 persons (1,127 living, 16 deceased) living in south central Texas who had documented environmental exposure to benzene (up to 66ppb) in tap water. As with all subregistries, face-to-face interviews were used to collect self-reported information for 25 general health status questions. Using computer-assisted telephone interviewing, the same health questions were asked I year (Followup 1, F1) and 2 years later (Followup 2, F2). The health outcome rates for Baseline and Followup I and 2 data collections for the Benzene Subregistry were compared with national norms, that is, the National Health Interview Survey (NHIS) rates. For at least one of the three reporting periods, specific age and sex groups of the Benzene Subregistry population reported more adverse health outcomes when compared with the NHIS population, including anemia and other blood disorders, ulcers, gall bladder trouble, and stomach or intestinal problems, stroke, urinary tract disorders, skin rashes, diabetes, kidney disease, and respiratory allergies. Statistically significant deficitsfor the Benzene Subregistry population overall were found for asthma, emphysema, or chronic bronchitis; arthritis, rheumatism, or other joint disorders; hearing impairment; and speech impairment. No statistically significant differences between the two populations were seen for the outcomes hypertension; liver disease; mental retardation; or cancer. These results do not identify a causal relationship between benzene exposure and adverse health effects; however, they do reinforce the need for continued followup of registrants.
Discrete Graphical Models in Social Mobility Research - A Comparative Analysis of American, Czechoslovakian and Hungarian Mobility before the Collapse of State Socialism
Authors: Németh Renáta , Rudas Tamás
Published: September 2013

Variants of path models have been widely used for the analysis of the social status attainment process. The methods presented here differ from earlier approaches in several ways. Social status is considered a categorical variable and path models are developed starting from graphical models, using the marginal log-linear approach. Overall model fit may be tested by standard techniques. Under these models, the status attainment process is completely characterized by a set of parameters that measure the strengths of the relevant effects. This is in sharp contrast with estimating and interpreting ad hoc parameters, without paying attention to overall model fit and to other effects influencing the process. The method is applied to the social status attainment process in the USA, Hungary and Czechoslovakia at the end of the last century, and shows that policies in the latter socialist countries to prevent status inheritance had little success.
Ecole thématique CNRS « Etudier les réseaux sociaux », Porquerolles,10-14 septembre 2012
Authors: Grossetti Michel , Lemercier Claire , Bidart Claire , Bertrand Michel
Published: September 2013

CNRS Thematic School “Studying Social Networks”, Porquerolles, 10-14 September 2012: Following the success of the first CNRS Summer School on social networks in Cargèse, Corsica, 15-20 September 2008 (see the preceding article by Alain Degenne), the organizers and the CNRS decided that a second thematic school should be organized on the Mediterranean island of Porquerolles, this time with more of a concentration on social sciences other than sociology, and specifically on history. This is a report on this rather successful second thematic school on social networks.
Alain Desrosières
Authors: van Meter Karl M.
Published: September 2013

Alain Desrosières: This colleague, friend and internationally known specialist on the history and development of statistics, especially in the social sciences, died on 15 February 2013 before we could publish his article which follows in English. This is a short description of his life and work.
The History of Statistics as a Genre
Authors: Desrosières Alain
Published: September 2013

To what extent does the history of statistics belong to the literary genre of “social constructions”? Does this genre include the development of national statistics? This brief historical summary of selected steps in the social uses of history and, more recently, of the history of science, can be helpful for examining the different ways in which the history of statistics has been written and used. It includes five sections: The First Period of National Statistical Histories (1800-1920); The Difficulties of Statistical Internationalism; The History of the Mathematization of Statistics; The New Wave of National-Statistics History (since 1975); The Bielefeld Group and the “Probabilistic Revolution”.
Forms and Modes of Apprehending Interdisciplinarity
Authors: Collinet Cécile , Terral Philippe , Trabal Patrick , Delalandre Matthieu
Published: September 2013

This article considers the interdisciplinary character of sports sciences, which holds a double challenge. On one hand, demonstrating how the analysis of a corpus of scientific texts contributes – without exhausting the magnitude of the scientific work – to a better knowledge of a field of interdisciplinary research: sports sciences. On the other hand, on a methodological level, tools and computer strategies have been developed in order to analyze textual data. This article reveals how interdisciplinarity explicitly appears in scientific papers, not only as a discussion topic, but also as an organizational watchword in sports sciences. Besides, the analysis of this corpus helps to finely characterize active forms of interdisciplinary work organized around hybrid disciplines or specific research subjects.