Assaying the Effect of Levodopa on the Evaluation of Risk in Healthy Humans

In humans, dopamine is implicated in reward and risk-based decision-making. However, the specific effects of dopamine augmentation on risk evaluation are unclear. Here we sought to measure the effect of 100 mg oral levodopa, which enhances synaptic release of dopamine, on choice behaviour in healthy humans. We use a paradigm without feedback or learning, which solely isolates effects on risk evaluation. We present two studies (n = 20; n = 20) employing a randomised, placebo-controlled, within-subjects design. We manipulated different dimensions of risk in a controlled economic paradigm. We test effects on risk-reward tradeoffs, assaying both aversion to variance (the spread of possible outcomes) and preference for relative losses and gains (asymmetry of outcomes - skewness), dissociating this from potential non-specific effects on choice randomness using behavioural modelling. There were no systematic effects of levodopa on risk attitudes, either for variance or skewness. However, there was a drift towards more risk-averse behaviour over time, indicating that this paradigm was sensitive to detect changes in risk-preferences. These findings suggest that levodopa administration does not change the evaluation of risk. One possible reason is that dopaminergic influences on decision making may be due to changing the response to reward feedback.     

An Assessment of the Carcinogenic Potential of Trichloroethylene in Humans

Controversy surrounds the assessments of carcinogenic potential associated with human exposure to trichloroethylene (TCE). The American Conference of Governmental Industrial Hygienists states that TCE is “not suspected to be a human carcinogen.” In contrast, the International Agency for Research on Cancer has classified TCE as a probable human carcinogen, based primarily on the results of animal toxicity studies. Chronic high-dose TCE exposures cause hepatic and pulmonary tumors in mice and renal tumors in rats. Human epidemiology studies, however, do not support a causal association between exposure to TCE at environmentally relevant levels and cancers of the lung, liver, or kidney. The apparent discrepancy between the animal data and the human data can be explained by (1) differences in TCE exposure levels between laboratory animals and humans, (2) species-specific differences in TCE metabolism, and (3) other species-specific mechanisms involved in the development of cancer in rodents. This paper critically assesses the experimental and epidemiological data relevant to the carcinogenic potential of TCE. From the analysis, we conclude that TCE exposure at concentrations likely to be encountered in most environmental media is not likely to cause liver, lung, or kidney cancers in humans.     

Investigating the Contribution of Peri-domestic Transmission to Risk of Zoonotic Malaria Infection in Humans

BackgroundIn recent years, the primate malaria Plasmodium knowlesi has emerged in human populations throughout South East Asia, with the largest hotspot being in Sabah, Malaysian Borneo. Control efforts are hindered by limited knowledge of where and when people get exposed to mosquito vectors. It is assumed that exposure occurs primarily when people are working in forest areas, but the role of other potential exposure routes (including domestic or peri-domestic transmission) has not been thoroughly investigated.Conclusions/SignificanceThis study shows there is a possibility that humans can be exposed to P. knowlesi infection around their homes. The vector is highly exophagic and few were caught indoors indicating interventions using bednets inside households may have relatively little impact.     

Mapping Risk of Nipah Virus Transmission from Bats to Humans in Thailand

Nipah virus (NiV) is a zoonotic virus that can pose a serious threat to human and livestock health. Old-world fruit bats (Pteropus spp.) are the natural reservoir hosts for NiV, and Pteropus lylei, Lyle’s flying fox, is an important host of NiV in mainland Southeast Asia. NiV can be transmitted from bats to humans directly via bat-contaminated foods (i.e., date palm sap or fruit) or indirectly via livestock or other intermediate animal hosts. Here we construct risk maps for NiV spillover and transmission by combining ecological niche models for the P. lylei bat reservoir with other spatial data related to direct or indirect NiV transmission (livestock density, foodborne sources including fruit production, and human population). We predict the current and future (2050 and 2070) distribution of P. lylei across Thailand, Cambodia, and Vietnam. Our best-fit model predicted that central and western regions of Thailand and small areas in Cambodia are currently the most suitable habitats for P. lylei. However, due to climate change, the species range is predicted to expand to include lower northern, northeastern, eastern, and upper southern Thailand and almost all of Cambodia and lower southern Vietnam. This expansion will create additional risk areas for human infection from P. lylei in Thailand. Our combined predictive risk maps showed that central Thailand, inhabited by 2.3 million people, is considered highly suitable for the zoonotic transmission of NiV from P. lylei. These current and future NiV transmission risk maps can be used to prioritize sites for active virus surveillance and developing awareness and prevention programs to reduce the risk of NiV spillover and spread in Thailand.

     

A Simple Bioassay for Chemicals Active to the Photosynthetic or Respiratory Systems of Plants

After male rats of the Sprague Dawley strain, 5 weeks old, were fed a 20% casein diet with or without 0.5% nicotinamide for 13 days, 180 mg/kg body weight of alloxan was injected in- traperitoneally into the rats. The rats were kept for 18 days with the same diet. The level of blood glucose was increased 6-fold in the group on a 20% casein diet by the injection of alloxan, while there was only a 2-foid increase in the group on a nicotinamide-containing diet and the decreased body weight was also lower in the group on the nicotinamide diet than the group on the casein diet. The body weight was indirectly related to the concentration of blood glucose. A marked increase was observed in the activities of tryptophan oxygenase, aminocarboxymuconate-semialdehyde decarboxylase, and nicotinamide methyltransferase upon the injection of alloxan with both diets; on the other hand, the activities of kynureninase and NAD⁺ synthetase were decreased by the injection of alloxan. The activity of kynurenine aminotransferase increased in the group on the 20% casein diet by the injection of alloxan, while in the group on the nicotinamide-containing diet its activity was not increased by the injection. These changes in the above enzyme activities mean that the conversion ratio from tryptophan to niacin is lower in the alloxan diabetic rat than normal rat. It was found that the activities of tryptophan oxygenase, aminocarboxymuconate-semialdehyde decarboxylase, and nicotinamide methyltransferase were directly related to the concentration of blood glucose, and that the activities of kynureninase and NAD⁺ synthetase were inversely related. There was no difference in the activities of 3-hydroxyanthranilic acid oxygenase and nicotinamide mononucleotide adenylyltransferase upon the injection of alloxan with both diets.     

Incorporating Information on Bioavailability of Soil-Borne Chemicals into Human Health Risk Assessments

Definition of the term bioavailability varies in the environmental sciences. In human health risk assessment, bioavailability is defined as the fraction of the dose of chemical delivered that is absorbed into the systemic circulation. Bioavailability can be expressed as either absolute or relative bioavailability, and both are important in calculating risks from contaminants in soils. Bioavailability of chemicals is addressed in all risk assessments, although not always in a transparent manner. Because data on bioavailability are limited, approximations and assumptions regarding chemical uptake are extensively used. The risk assessment process could benefit from new information on the bioavailability of chemicals, but there are important questions about the best means to develop this information and how it should be used. To foster discussion on these issues, three articles are presented in this issue of the journal offering different perspectives on bioavailability method development, validation, and use.     

Evaluation of Available Energy of Aliphatic Chemicals by Rats

Bioassy procedure to evaluate biologically available energy of chemicals applicable to rats was established, and available energy of 36 chemicals was determined and compared with that estimated by chicks previously. Rats can utilize energy of propionic and butyric acids and n-hexyl propionate and butyrate well, while chicks cannot. Succinic acid, lauryl alcohol and dilauryl succinate at 5% dietary level were available by rats, though at 10% level lauryl alcohol was toxic. Ethyl lactate, octyl and decyl acetates and 1,2-propanediol dilaurate were available by both rats and chicks. Availability of other 6 esters including ethyl succinate and citrate was low. Availability and digestibility of aldehydes by rats were also low.     

Humans introduce viable seeds to the Arctic on footwear

Expanding visitation to Polar regions combined with climate warming increases the potential for alien species introduction and establishment. We quantified vascular plant propagule pressure associated with different groups of travelers to the high-Arctic archipelago of Svalbard, and evaluated the potential of introduced seeds to germinate under the most favorable average Svalbard soil temperature (10°C). We sampled the footwear of 259 travelers arriving by air to Svalbard during the summer of 2008, recording 1,019 seeds: a mean of 3.9 (±0.8) seeds per traveler. Assuming the seed influx is representative for the whole year, we estimate a yearly seed load of around 270,000 by this vector alone. Seeds of 53 species were identified from 17 families, with Poaceae having both highest diversity and number of seeds. Eight of the families identified are among those most invasive worldwide, while the majority of the species identified were non-native to Svalbard. The number of seeds was highest on footwear that had been used in forested and alpine areas in the 3 months prior to traveling to Svalbard, and increased with the amount of soil affixed to footwear. In total, 26% of the collected seeds germinated under simulated Svalbard conditions. Our results demonstrate high propagule transport through aviation to highly visited cold-climate regions and isolated islands is occurring. Alien species establishment is expected to increase with climate change, particularly in high latitude regions, making the need for regional management considerations a priority.     

Risk Assessment on the Carcinogenic Potential of Hybridoma Cell DNA: Implications for Residual Contaminating Cellular DNA in Biological Products

The aim of this study was to evaluate the possible carcinogenic potential of residual DNA derived from immortalized and possibly tumorigenic cell lines due to activated oncogenic sequences (oncogenes). These cell lines have been used for the production of biologicals, i.e. monoclonal antibodies, lymphokines and vaccines. The authors used hybridoma DNA as a first model. For this reason experiments in two species were performed, namely in 3–4 week-old female Balb/c mice and newborn Riv:TOX rats. Doses of 250 μg DNA, derived from Balb/c hybridoma cells, were injected subcutaneously (s.c.) in 200 mice. These mice also received a s.c. injection of the solvent only (TE buffer) at another site of the back skin (negative control for local tumour development). An additional group of 50 mice was treated intraperitoneally (i.p.) with the solvent only to serve as a negative control group for possible systemic tumorigenic effects. Doses of 5 μg plasmid pPy1 DNA, containing the entire Polyoma virus genome, served as positive control and were injected s.c. and i.p. in 20 and 50 mice, respectively. Doses of 50 μg hybridoma DNA of 5 μg pPy1 DNA were injected s.c. in rats too, using nine animals per group. During the experiment, animals were observed weekly, especially for the occurrence of subcutaneous tumours at the injection sites. The mouse study was terminated after more than 2 years, the rat study after 1 year. Gross necropsy was performed on all animals and histopathological examination of grossly suspected neoplastic lesions was performed.In the mouse experiment, tumour development at the s.c. injection site of the DNA was observed in one out of 20 animals in the pPy1-treated positive control group (neurofibrosarcoma) and one out of 200 animals in the hybridoma DNA-treated group (haemangioma-like lesion). Tumour development at or near the s.c. injection site of the solvent only was observed in two out of 200 animals.In the rat study none out of nine hybridoma DNA-treated rats developed tumours at the injection site, while three out of nine rats of the positive control group, injected with the pPy1 DNA, showed local tumour development (benign and malignant soft tissue tumours).It is considered that, at the high dose and numbers of animals tested, parenteral administration of hybridoma DNA does not induce local tumour development. Furthermore, no indications were found for systemic carcinogenic potential of the hybridoma DNA used.Based on a worst case approach of our data, the oncogenic risk of 100 pg residual DNA was estimated to be 2×10⁻⁹, a value intermediate of the estimations of the WHO (1987) and the Dutch Health Council (1988) 5×10⁻¹¹and 2×10⁻⁷, respectively. Therefore, it is unlikely that the risk of 100 pg of DNA derived from other immortalized cell lines will exceed the level of generally accepted cancer risk of 10⁻⁶.     

Assessment of Carcinogenic Risk and Non-Carcinogenic Health Hazard from Exposure to Toxicants in Water from the Southwestern Coastal River System in Ghana

This study evaluated cancer risk and non-cancer human health hazard from exposure to the toxicants such as As, Cu, Pb, Zn, Mn, and CN in water from a southwestern river system in Ghana that drains through gold mining areas, using 108 water samples collected with random sampling techniques and analyzed in accordance with standard methods of chemical analysis outlined by the U.S. Environmental Protection Agency (USEPA). The concentrations of Cu and Zn were within World Health Organization and USEPA guideline values; Mn, free cyanide, As, and Pb values in most cases either exceeded USEPA and WHO values or both. The concentrations of the toxicants were used as input parameters in the cancer and non-cancer study that was conducted in line with USEPA risk assessment guidelines. The results of As cancer health risk revealed higher risk cases in two locations (Potroase and Dominase); non-cancer health risk for As was higher in 10 of the 14 locations, with other metals being of health concern at few locations in the study area. In conclusion, the findings of this study hold several policy implications as residents of mining communities still depend on these water bodies as their source of drinking water.