Mark Johnson

Mark Johnson
United States Army · Toxicology

About

131
Publications
9,551
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2,224
Citations
Citations since 2016
25 Research Items
887 Citations
2016201720182019202020212022020406080100120140
2016201720182019202020212022020406080100120140
2016201720182019202020212022020406080100120140
2016201720182019202020212022020406080100120140

Publications

Publications (131)
Article
Problem formulation is a critical initial step in planning risk assessments for chemical exposures to wildlife. It is used either explicitly or implicitly in various jurisdictions to include registration for new pesticides, evaluation of new and existing chemicals released to the environment, and characterization of impact when chemical releases ha...
Article
Per‐ and Polyfluoroalkyl Substances (PFAS) are a group of highly fluorinated synthetic chemicals that were originally developed for uses as surfactants and surface protectors. Increasingly, specific substances of this class are being found in environmental media (e.g. surface water, soils, sediments, food sources) and concerns regarding exposure to...
Article
Dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ) are constituents of insensitive munitions being developed to minimize the acute hazards associated with non-intentional detonation of warheads. Although a reference dose (RfD) has been established for NQ and occupational exposure levels have been developed for all thr...
Article
Development of toxicology-based criteria such as occupational exposure levels (OELs) are rarely straightforward. This process requires a rigorous review of the literature, searching for patterns in toxicity, biological plausibility, coherence, and dose–response relationships. Despite the direct applicability, human data are rarely used primarily be...
Article
Many state and Federal environmental and health agencies have developed risk‐based criteria for assessing the risk of adverse health effects of PFAS exposure to humans and the environment. However, the criteria that have been developed vary; drinking water criteria developed for PFOA, for example, can vary by up to 750. This is due to differences a...
Article
Understanding risks to terrestrial wildlife species from exposure to chemicals in the environment requires knowledge of how species make habitat decisions and how subsequent exposure events occur. Heterogeneity of chemical distribution and of habitat quality can influence exposure. Previous studies in birds have shown that individually–based, spati...
Article
Full-text available
To evaluate the effects of chronic exposure to 3-nitro-1,2,4-triazol-5-one (nitrotriazolone, NTO), male and female rats were given ad libitum access to NTO in drinking water at concentrations of 0, 36, 110, 360, 1100, and 3600 mg/L for one year. NTO did not affect body weight, body weight gain, or food consumption in either sex. No treatment-relate...
Chapter
Sustainable use of testing and training ranges within the U.S. Department of Defense is a critical goal in maintaining a ready force capable of meeting future security requirements. Large land areas are required for these purposes, many of which support valuable resources to local communities in terms of maintaining ecosystem services, preserving r...
Chapter
Proactive assessment of environmental, safety, and occupational health hazards is essential and required in the production and use of new weapon systems and platforms; however, few specific data requirements exist. Additionally, no specific requirements exist for research, development, testing, and evaluation (RDT&E) of new technologies. Any effect...
Article
Full-text available
Background The health and resilience of species in natural environments is increasingly challenged by complex anthropogenic stressor combinations including climate change, habitat encroachment, and chemical contamination. To better understand impacts of these stressors we examined the individual- and combined-stressor impacts of malaria infection,...
Article
Full-text available
Substances used as explosives in munitions by the military often result in environmental releases through manufacturing, testing, training, and combat activities. The toxicity of 3-nitro-1,2,4-triazol-5-one (nitrotriazolone or NTO) was evaluated following oral exposure in Japanese quail (Coturnix japonica) to determine if environmental releases res...
Article
Acute systemic toxicity data are used by a number of U.S. federal agencies, most commonly for hazard classification and labeling and/or risk assessment for acute chemical exposures. To identify opportunities for the implementation of non-animal approaches to produce these data, the regulatory needs and uses for acute systemic toxicity information m...
Article
Full-text available
New explosive formulations are being developed to be less sensitive to impact and inadvertent explosion, increasing safety for the warfighter. Since testing and training make environmental releases imminent, the toxicity of 3-nitro-1,2,4-triazol-5-one (NTO), a component of Insensitive Munitions eXplosive (IMX) formulations, was assessed in a one-ge...
Article
Bioaccumulation models quantify the relationship between sediment and water exposure concentrations and resulting tissue levels of chemicals in aquatic organisms, and represent a key link in the suite of tools used to support decision making at contaminated sediment sites. Predicted concentrations in the aquatic food web provide exposure estimates...
Article
Environmental health risk assessments often involve assessing the potential health effects of exposure to multiple chemicals at once (i.e., complex mixtures). Because the possible number of chemical combinations is very large, few controlled in vivo toxicological studies with chemical mixtures are relevant or practical. In lieu of specific mixture...
Article
Historically, ecological risk assessments have rarely included amphibian species, focusing preferentially on other aquatic (fish, invertebrates, algae) and terrestrial wildlife (birds and mammal) species. Often this lack of consideration is due to a paucity of toxicity data, significant variation in study design, uncertainty with regard to exposure...
Article
New insensitive munitions are being developed to minimize the acute hazards associated with non-intentional detonation of warheads. Two components often used in munition formulations have limited toxicity data, i.e., 3-nitro-1,2,4-triazol-5-one (NTO) and 2,4-dinitroanisole (DNAN). Oral acute, subacute, and subchronic studies have recently been comp...
Article
Full-text available
Nitrotriazolone (1,2,4-triazol-5-one; NTO), an insensitive, energetic material used in explosive formulations, induced testicular toxicity and oligospermia in repeated-dose oral toxicity tests in rats. To evaluate whether NTO produces additional reproductive and developmental effects, a modified extended one-generation reproductive toxicity test wa...
Chapter
Trinitrotoluene (2,4,6-trintrotoluene, TNT) is an extensively used explosive, which has been detected in soil and water at military sites and at munitions manufacturing and training operations. TNT contamination may be hazardous to animal health. The toxicity data of TNT on wildlife were evaluated using the benchmark dose procedure on sensitive adv...
Chapter
Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (or high melting explosive, HMX) is an N-nitrated, eight-member heterocyclic ring compound that is used in military munitions. Occupational and environmental contamination might be due to the manufacturing process; environmental discharge of waste waters; during the manufacture of explosives; and in...
Chapter
Pentaerythritol tetranitrate (PETN) is an explosive used as the primary ingredient in detonating fuses and as a component in some plastic explosives. As a nitrate ester, PETN is structurally similar to nitroglycerin in its pharmacological (vasodilatory) and explosive properties. The few toxicity studies conducted have shown PETN to be relatively be...
Chapter
Historical and current examples exist where valued wildlife species were harmed from exposure to chemicals that initially resulted from human events. Inadvertent and indirect exposures to pesticides, chemical residues, and waste streams have resulted in adverse effects that have affected populations of wildlife species. Many jurisdictions have regu...
Conference Paper
Ecological screening levels and remediation goals for wildlife are often developed using food-web models based on conservative assumptions of exposure and toxicity. The toxicity reference values (TRVs) underlying these concentration goals are typically based on no- or lowest observed adverse effect levels (NOAELs/LOAELs) from available laboratory t...
Article
Full-text available
Field-based studies are an essential component of research addressing the behavior of organic chemicals, and a unique line of evidence that can be used to assess bioaccumulation potential in chemical registration programs and aid in development of associated laboratory and modeling efforts. To aid scientific and regulatory discourse on the applicat...
Article
Full-text available
Background: A systems toxicology investigation comparing and integrating transcriptomic and proteomic results was conducted to develop holistic effects characterizations for the wildlife bird model, Northern bobwhite (Colinus virginianus) dosed with the explosives degradation product 2-amino-4,6-dinitrotoluene (2A-DNT). A subchronic 60d toxicology...
Article
Insensitive munitions (IMs) offer increased safety due to their "insensitivity" to unintended detonation relative to historically used formulations such as 2,4,6-trinitrotoluene (TNT). Dinitroanisole (DNAN) is an IM constituent, and its solubility and stability warrant investigations of potential toxicological hazard related to manufacturing discha...
Article
Full-text available
Half of the 18 human integrins α subunits have an inserted αI domain yet none have been observed in species that have diverged prior to the appearance of the urochordates (ascidians). The urochordate integrin αI domains are not human orthologues but paralogues, but orthologues of human αI domains extend throughout later-diverging vertebrates and ar...
Article
Full-text available
Proteins with EF-hand calcium-binding motifs are essential for many cellular processes, but are also associated with cancer, autism, cardiac arrhythmias, and Alzheimer's, skeletal muscle and neuronal diseases. Functionally, all EF-hand proteins are divided into two groups: (1) calcium sensors, which function to translate the signal to various respo...
Article
Full-text available
The explosive 3-nitro-1,2,4-triazol-5-one (NTO) is an insensitive formulation developed to replace high energetics that are susceptible to accidental detonation from heat, shock, and impact. Although studies have shown NTO to be nontoxic at acute exposures, recent subacute and subchronic tests have demonstrated effects on testes and subsequent sper...
Article
Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, d...
Article
Full-text available
The development of media-specific ecological values for risk assessment includes the derivation of acceptable levels of exposure for terrestrial wildlife (e.g., birds, mammals, reptiles, and amphibians). Though the derivation and subsequent application of these values can be used for screening purposes, there is a need to identify toxicological eff...
Article
Full-text available
Citrullinated collagen II (CII) is a well-known autoantigen in rheumatoid arthritis (RA). However, the direct effects of CII citrullination on cell behavior have not been described. To study whether citrullination of CII could affect cellular functions, we measured the adhesion of 3 different cell types (human Saos2 osteosarcoma cells, human synovi...
Article
Full-text available
Background: Traditional animal toxicity tests can be time and resource intensive, thereby limiting the number of chemicals that can be comprehensively tested for potential hazards to humans and/or to the environment. Objective: We compared several types of data to demonstrate how alternative models can be used to inform both human and ecological...
Article
4-Amino-2-nitrotoluene (4A2NT; CAS 119-32-4) is a degradation product of 2,4-dinitrotoluene. The toxicity data on 4A2NT are limited. Therefore, we collected toxicity data from rats to assess environmental and human health effects from exposures. The approximate lethal dose for both sexes was 5000 mg/kg. A 14-day toxicity study in rats was conducted...
Article
Full-text available
The purpose of this study was to assess the toxicological effects of two munition compounds, 4-amino-2,6-dinitrotoluene (4A-DNT) and 1,3,5-trinitro-1,3,5-triazine (RDX), on three different bird species: two common toxicological model species-the Northern Bobwhite (Colinus virginianus) and the Japanese Quail (Coturnix japonica), and a representative...
Conference Paper
An integral component of the development of media-specific ecological values for risk assessment involves the derivation of safe levels of exposure for wildlife. Though the derivation and subsequent application of these values can be used for screening purposes, there is a need to identify the threshold for effects when making remedial decisions....
Article
Evaluation of multiple-stressor effects stemming from habitat degradation, climate change, and exposure to chemical contaminants is crucial for addressing challenges to ecological and environmental health. To assess the effects of multiple stressors in an understudied taxon, the western fence lizard (Sceloporus occidentalis) was used to characteriz...
Article
Sustainable use of military training ranges requires the development of compounds that have a minimal impact to the environment when used in a weapon system. Guanidinium 3,4-dinitropyrazolate (GDNP) is a novel explosive compound of interest for application in some weapon systems. Little is known of its toxicologic properties. To ensure the health o...
Article
Factors used in environmental remedial decision making concerning ecological risk are not well understood or necessarily consistent. Recent Records of Decision (RODs) for Army CERCLA sites were reviewed to select case studies where remedial management occurred in response to ecological risks. Thirty-four Army RODs were evaluated representing decisi...
Article
The consideration of multiple or cumulative sources of exposure to a chemical is important for adequately protecting human health. This assessment demonstrates one way to consider multiple or cumulative sources through the development of a relative source contribution (RSC) factor for the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), usi...
Article
RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) is an explosive used in military applications. It has been detected in ground water surrounding US military installations and at manufacturing facilities. RDX has been shown to produce hepatotoxicity, testicular, and neurological effects in animals, the latter also in humans. The current chronic oral re...
Article
Ascorbic acid (AA) enhances innate immunity, alters gene expression and functions as a co-factor in specific enzyme reactions. Birds are unique in that they can synthesise ascorbic acid whereas humans and rodents lack this ability. Diagnostic tests that currently exist to measure ascorbic acid levels in birds are time-consuming and expensive. In th...
Article
Ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN) are relatively insensitive explosive compounds that are being explored as safe alternatives to other more sensitive compounds. When used in combination with other high explosives they are an improvement and may provide additional safety during storage and use. The genetic tox...
Article
Full-text available
Sustainable use of training ranges requires the development of compounds that have a minimal impact on the environment when used in a weapon system. Triaminoguanidinium-1-methyl-5-nitriminotetrazolate (TAG-MNT) is a novel, explosive, military compound of interest for application in some weapon systems. Little is known of its toxicologic properties....
Article
Spatially explicit wildlife exposure models have been developed to integrate chemical concentrations dispersed in space and time, heterogeneous habitats of varying qualities, and foraging behaviors of wildlife to give more realistic wildlife exposure estimates for ecological risk assessments. These models not only improve the realism of wildlife ex...
Article
Full-text available
Small arms-range (SAR) soils can be contaminated with metals from spent copper (Cu)-jacketed bullets. Avian species are particularly at risk because they are exposed to lead (Pb) through ingestion of grit, soil intake from preening, or ingestion of contaminated food near ranges. Examination of the effects of Pb on birds at ranges have mainly focuse...
Article
3-Nitro-1,2,4-triazol-5-one (NTO) is an energetic explosive proposed for use in weapon systems, to reduce the sensitivity of warheads. In order to develop toxicity data for safety assessment, we investigated the genotoxicity of NTO, using a battery of genotoxicity tests, which included the Ames test, Chinese Hamster Ovary (CHO) cell chromosome aber...
Poster
Full-text available
Limitations on currently used models in ecological risk assessment have spawned demand for spatially explicit exposure models that hold promise of improving risk estimates. However, few example applications and a lack of compiled information about what is available may have affected use. These models offer a scientifically sound and technically inn...
Article
The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD(50) values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic exp...
Article
Recognition of the occupational hazards from exposure to the propellants hydrazine and monomethylhydrazine (MMH) has led to research into less toxic alternatives. Two hypergolic compounds, dimethylamino-2-ethylazide (DMAZ) and N,N,N',N'-tetramethylethanediamine (TMEDA), have been identified as possible replacements for MMH. We have obtained genotox...
Article
Full-text available
The limited availability of genomic tools and data for nonmodel species impedes computational and systems biology approaches in nonmodel organisms. Here we describe the development, functional annotation, and utilization of genomic tools for the avian wildlife species Northern bobwhite (Colinus virginianus) to determine the molecular impacts of exp...
Article
2-Amino-4,6-dinitrotoluene (2A-DNT) is a metabolite of the explosive 2,4,6-trinitrotoluene (TNT) which is present in the soil at numerous U.S. Army installations as the result of TNT manufacture or training activities. Although many avian species are known to inhabit areas where 2A-DNT has been found in the environment, no published studies of the...
Article
Interaction of blood platelets with vascular collagen is an initiating event in haemostasis and thrombus formation. Based on molecular modelling of human integrin alpha2I domain and cell-based screening assays we have developed sulfonamide derivatives, a mechanistically novel class of molecules. These molecules show antiplatelet efficacy by selecti...
Article
The use of lead in military and civilian small arms projectiles is widely acknowledged to have resulted in high soil lead concentrations at many small arms ranges. These ranges are often adjacent to wildlife habitat or have become habitat when no longer used. To assess the potential toxicity of lead to terrestrial amphibians in contaminated areas,...
Article
Full-text available
The explosive, octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine or high-melting explosive (HMX), has been found in soils in areas used for testing and training by the military. Many of these areas contain habitat for valued wildlife species. In an effort to better understand the environmental consequences from exposure, a reptilian (western fence l...