Toxicity of oral exposure to 2,4,6‐trinitrotoluene in the western fence lizard (<i>Sceloporus occidentalis</i>)

McFarland, Craig A.; Quinn, Michael J.; Bazar, Matthew A.; Remick, Amera K.; Talent, Larry G.; Johnson, Mark S.

doi:10.1897/07-312.1

Cited by 32 publications

(24 citation statements)

References 29 publications

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“…In the subchronic study, only 50% of the 5 mg/kg/d group survived 60 d. Similar findings were observed for lizards repetitively dosed with lower doses of trinitrotoluene (potential exposure pattern under natural conditions), demonstrating that frequency of exposure has a profound influence on toxicity [30]. In the subchronic study, only 50% of the 5 mg/kg/d group survived 60 d. Similar findings were observed for lizards repetitively dosed with lower doses of trinitrotoluene (potential exposure pattern under natural conditions), demonstrating that frequency of exposure has a profound influence on toxicity [30].…”

Section: Discussionsupporting

confidence: 76%

“…To date, this laboratory and others have determined that male lizards are more sensitive than females to the oral administration of selected munition compounds [19,30] (C.A. The parent compound (RDX) was administered orally for 14 consecutive days and adjusted as necessary for change in body weight measured on days 0, 3, 7, and 14.…”

Section: Preliminary Acute and Subacute (14-d) Experimentsmentioning

confidence: 99%

“…Spermatozoa were collected from the epididymis and vas deferens following euthanasia and immediately after dissecting tissues from the remaining urogenital tract [30]. Briefly, spermatozoa were released by mincing the tissues with scissors into 200 l of buffered Roswell Park Memorial Institute-1640 medium (Sigma Chemical).…”

Section: Analysis Of Spermatozoamentioning

confidence: 99%

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Toxic effects of oral hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine in the western fence lizard (Sceloporus occidentalis)

McFarland¹,

Quinn²,

Bazar³

et al. 2009

Enviro Toxic and Chemistry

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Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been widely used as an explosive in munition formulations, resulting in contamination of wildlife habitat on military installations. To estimate health effects for reptilian species, acute, subacute, and subchronic oral toxicity studies were conducted using the Western fence lizard (Sceloporus occidentalis). Estimated oral median lethal doses were 72 (95% confidence interval [CI], 49-106) mg/kg body weight (slope, 3.754) for males and 88 (95% CI, 65-119) mg/kg (slope, 4.525) for females. Toxicity from RDX suggested the neurological system as the critical target tissue. A 14-d subacute study followed with males dosed orally with RDX (corn oil) at 0, 10, 20, 25, 30, 45, and 60 mg/kg/d. Signs of toxicity frequently included a characteristic body posture. A significant dose-survival relationship was seen over the range of doses, with a significant decrease in survival at 20 mg/kg/d. Males in the 60-d subchronic study were dosed at 0, 1, 2.5, 5, 8, and 11 mg/kg/d, and signs of toxicity included lethargy, cachexia, and anorexia. Survival was decreased at 8 and 11 mg/kg/d. Reduced growth rate and food consumption occurred at 5 mg/kg/d. Brain tissue was assayed for RDX when seizures were observed at a residue concentration of at least 18 microg/g. No abnormalities were observed in the hematologic indices, whereas plasma proteins were reduced. Hepatic enlargement and decreased testes mass occurred at 8 and 11 mg/kg/d. Plasma testosterone concentrations, sperm counts, and motility measures were variable for all treatment levels. Based on survival, growth rate, food intake, and testes to brain weight ratios, these data suggest a lowest-observed-adverse effect level of 5 mg/kg/d and a no-observed-adverse effect level of 2.5 mg/kg/d.

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Section: Discussionsupporting

confidence: 76%

Section: Preliminary Acute and Subacute (14-d) Experimentsmentioning

confidence: 99%

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Toxic effects of oral hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine in the western fence lizard (Sceloporus occidentalis)

McFarland¹,

Quinn²,

Bazar³

et al. 2009

Enviro Toxic and Chemistry

Self Cite

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“…The methods generally followed those previously described by McFarland et al (2008) (McFarland et al, 2008). Tissue sections were trimmed, placed in cassettes, and embedded in paraffin.…”

Section: Histopathological Analysismentioning

confidence: 99%

Tissue distribution, metabolism and hepatic tissue injury in Chinese lizards (Eremias argus) after a single oral administration of lambda-cyhalothrin

Chang

Wang

et al. 2016

Environmental Pollution

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a b s t r a c tLambda-cyhalothrin (LCT) is a widely used pyrethroid with neurotoxicity. However, little is known about the toxicokinetics of LCT in reptiles. In this study, the absorption, distribution, metabolism and excretion of LCT in Chinese lizards (Eremias Argus) were determined following a single dose (10 mg kg À1 ) treatment. In the liver, brain, gonads and skin, LCT levels peaked within several hours and then decreased rapidly. However, the concentration of LCT gradually increased in the fat tissue. More than 90% of the LCT dose was excreted in the faeces. One LCT metabolite, 3-phenoxybenzoic acid (PBA), was detected in lizard plasma and tissues. PBA preferentially accumulates in the brain and plasma. The half-life of PBA in the brain was 3.2 days, which was 35.4-fold greater than that of LCT. In the plasma, the concentration of PBA was significantly higher than that of LCT. The bioaccumulation of LCT in tissues was enantioselective, and the enantiomeric fractions (EF) ranged from 0.72 to 0.26. The preferential accumulation of enantiomers changed according to exposure time, but the reasons behind this phenomenon were not clear. For pathological analysis, vacuolation of the cytoplasm and large areas of necrosis were observed in the liver sections after 168 h of dosing. The liver tissues exhibited both decreases in the hepatosomatic index and histopathological lesions during the exposure period. In this study, the effect concentration of LCT in lizards was 200-fold lower than its LD 50 value used in risk assessments for birds. These results may provide additional information for the risk assessment of LCT for reptiles and indicate that birds may not be an ideal surrogate for reptile toxicity evaluation.

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“…The widespread use of RDX and HMX after World War II has resulted in their presence in at least 16 of the 1397 hazardous waste sites on the National Priorities List [24], and they are found as pollutants in soil [25,26] and the air [27] around or near munitions manufacturing sites. In mammals, the clinical outcome of oral administration of RDX is the rapid onset of seizures (skeletal muscle convulsions) and increased salivation in humans [28], rats [29][30][31], mice [32], pigs [33], northern bobwhite quail [34], and western fence lizards [35]. Recently, evidence that RDX binds to the γ-aminobutyric acid type A receptor (GABA A R) instead of the NMDAR was presented [36].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of natural and nitramine binding energies to 3-D models of the S1S2 domains in the N-methyl-D-aspartate receptor

Ford-Green

Isayev

Gorb³

et al. 2011

J Mol Model

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Overactivation of the N-methyl-D-aspartate receptor (NMDAR) in postsynaptic neurons leads to glutamate-related excitotoxicity in the central nervous system of mammals. We have built 3-D models of each domain for the universal screening of potential toxicants and their binding mechanisms. Our docking results show that the calculated pK (i) values of glycine and L: -glutamate significantly increase (>1) when the NR1 and NR2A S1S2 domains are closing, respectively. Inversely, D: -cycloserine (DCS) and 5,7-dichlorokynurenic acid (5,7-DCKA) do not show such a dependence on domain closure. Replica exchange molecular dynamics (REMD) confirmed 5 different conformational states of the S1S2 domain along the 308.2 K temperature trajectory. Analysis of residue fluctuations during this temperature trajectory showed that residues in loop 1, loop 2, the amino terminal domain (ATD), and the area linked to ion channel α-helices are involved in this movement. This further implicates the notion that efficacious ligands act through S1S2 lobe movement which can culminate in the opening or closing of the ion channel. We further tested this by docking hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) to the S1S2 domain. Our results predict that these nitramines are not efficacious and thus do not produce excitoxicity when they bind to the S1S2 domain of the NMDAR.

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Toxicity of oral exposure to 2,4,6‐trinitrotoluene in the western fence lizard (Sceloporus occidentalis)

Cited by 32 publications

References 29 publications

Toxic effects of oral hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine in the western fence lizard (Sceloporus occidentalis)

Toxic effects of oral hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine in the western fence lizard (Sceloporus occidentalis)

Tissue distribution, metabolism and hepatic tissue injury in Chinese lizards (Eremias argus) after a single oral administration of lambda-cyhalothrin

Evaluation of natural and nitramine binding energies to 3-D models of the S1S2 domains in the N-methyl-D-aspartate receptor

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