Oral Irritation Research Articles

Neonicotinoid insecticide exposures reported to six poison centers in Texas

Neonicotinoids are a relatively newer class of insecticide. Used primarily in agriculture, neonicotinoids are also used for flea control in domestic animals. Information on human exposures to neonicotinoids is limited. Neonicotinoid exposures reported to Texas poison centers during 2000-2012 were identified and the distribution by selected factors examined. Of 1,142 total exposures, most products contained imidacloprid (77%) or dinotefuran (17%). The exposures were seasonal with half reported during May-August. The most common routes of exposure were ingestion (51%), dermal (44%), and ocular (11%). The distribution by patient age was 5 years or less (28%), 6-19 years (9%), 20 years or more (61%), and unknown (2%); and 64% of the patients were female. Of all, 97% of the exposures were unintentional and 97% occurred at the patient's own residence. The management site was on-site (92%), already at/en route to a health care facility (6%), and referred to a health care facility (2%). The medical outcomes included no effect (22%), minor effect (11%), moderate effect (1%), not followed judged nontoxic (14%), not followed minimal effects (46%), unable to follow potentially toxic (1%), and unrelated effect (4%). The most commonly reported adverse clinical effects were ocular irritation (6%), dermal irritation (5%), nausea (3%), vomiting (2%), oral irritation (2%), erythema (2%), and red eye (2%). The most frequently reported treatments were dilution/wash (85%) and food (6%). In summary, these data suggest that the majority of neonicotinoid exposures reported to the poison centers may be managed outside of health care facilities with few clinical effects expected.

Positive control for cytotoxicity evaluation of dental vinyl polysiloxane impression materials using sodium lauryl sulfate

Objectives. Vinyl polysiloxane (VPS) is elastomeric dental impression material which, despite having very few reports of adverse reactions, has shown high levels of cytotoxicity that is difficult to be interpreted without referencing to the positive control material. Therefore, in this study, positive control VPS was developed using sodium lauryl sulfate (SLS) for the reference of cytotoxicity test. Materials and methods. The positive control VPS with SLS was formed with a different proportion of SLS (0, 1, 2, 4, 8 and 16 wt%) added to the base. The cytotoxicity test was then carried out using the extractions or dilutions of the extractions from each of the test samples using murine fibroblast cells (L929). Results. The final product of positive control VPS behaved similar to commercially available VPS; being initially liquid-like and then becoming rubber-like. Ion chromatography showed that the level of SLS released from the product increased as the proportion of added SLS increased, consequently resulting in an increased level of cytotoxicity. Also, the commercially available VPS was less cytotoxic than the positive control VPS with more or equal to 2 wt% of SLS. However, even the VPS with the highest SLS (16 wt%) did not cause oral mucosa irritation during the animal study. Conclusions. The positive control VPS was successfully produced using SLS, which will be useful in terms of providing references during in vitro cytotoxicity testing.

Gentian Violet-Induced Oral Irritation

A 67 year old female was referred to the Department of oral medicine due to the lesions on the gingiva where she applied 1% aqueous gentian violet due to the gingival inflammation. She applied gentian violet d uring two days, two times a day. The pain was worsening as well as extension of the lesions. She was advised to stop applying gentian violet and was given mouthrinse consisting of hexetidinum, methylprednisolone and xylocaine to be used three times a day. After 10 days the lesions completely healed. This case highlights the fact the commonly prescribed agents might also induce oral toxic/iritational reactions in the oral cavity.

Acute methotrexate ingestions in adults: a report of serious clinical effects and treatments.

Objective. Limited reported data have reports effects after acute ingestion of methotrexate. Treatment recommendations do not differentiate between exposure routes. Our objective was to determine the frequency of significant toxicity effects and use of therapy after methotrexate ingestion in adults. Methods. We performed a retrospective study on adult cases reported to 6 poison centers over 6 years (2000–2005) which exceed 180,000 exposures/year. Variables collected included demographics, dosages ingested, coingestions, clinical effects, and therapies with outcomes. Results. Sixty-three patients examined over the 6-year period met inclusion criteria. No patient in the series received dialysis or died. The mean dose ingested for all patients was 24 mg (range 2.5–100 mg) and the mean dose for suicidal ingestions was 47.5 mg (12.5–100 mg). The most common clinical effects were abdominal pain, oral irritation, throat irritation, nausea, dizziness, and headache. Nine patients received folinic acid and 3 patients received sodium bicarbonate. No patient developed renal failure, bone marrow suppression, seizure, or coma. No patient died or received dialysis. Conclusion. In our series of patients from 6 poison centers over six years, 63 cases of acute adult methotrexate ingestions were reported. Methotrexate toxicity from ingestion in adults was uncommon and rarely toxic.

Preparation of the Silicone-Modified Antimicrobial Polyethylene Endotracheal Tube (PE ETT)

Polyethylene endotracheal tube (PE ETT) antimicrobial coating has been proved to be a more effective method to prevent endoluminal biofilm formation. A transparent silicone-modified antimicrobial PE ETT was obtained by coating SiO2/KH570/MTES/Ag-SiO2 solution prepared by chemical mixing Ag-SiO2 and SiO2/KH570/MTES solution by means of dip-coating method, followed by drying. All the films were characterized by various techniques including Pencil Hardness Tester, IR, SEM, UV-vis, and ICP-MS. The results indicated that the TEOS/KH570/MTES/Ag-SiO2 (15:6:1:0.6~1.0) films, which exhibit the simple solution-processable film formation on PE ETT, show homogeneous morphology, and have the high transmittance of above 87%, high hardness of 5H, strong adhesion. Furthermore, the silicone-modified antimicrobial PE ETTs show excellent antimicrobial property with the sterilization rate up to 93.5%, it demonstrates that the antimicrobial films have excellent biocompatibility and potent antimicrobial activity against protein adhesion. Pyrogen test, hemolysis test and oral mucous irritation test results are fit for biosecurity use requirement for biological materials. So, silicone-modified antimicrobial PE ETT is hoped to be used in the field of medical materials and can be used as an efficient and economical method to extend the service life of the PE ETT.

Clinical and laboratory evaluation of dogs experimentally intoxicated with toad venom

This study aimed to evaluate the clinical and laboratory aspects of dogs intoxicated with toad poison. Overall, 20 male and female, adult healthy dogs of undefined breed were used and divided into two groups: control (n = 5) and intoxicated with toad venom (n = 15). The dogs were submitted to anesthesia induction with thiopental and maintained on inhalation anesthesia with 3% isoflurane during the evaluation and data collection period. In this period, animals in the control group received saline and the animals in the intoxicated group received an aliquot of toad venom through orogastric probe. Samples for hematological, serum biochemical and blood gas analyses were collected. During the evaluation, drooling, oral mucosa irritation, defecation, urination, congestion and hyperemia of the oral mucosa were observed. Intoxication due to bufotoxin caused evident gastroenteritis and neurological alterations with variable signs. Toad venom did not cause renal injury and may be considered non-nephrotoxic in the present experimental conditions. The intoxicated animals showed a slight liver change measured by the ALT and ALP values, and blood gas analysis showed that various acid-base balance changes may occur.

Oral Tissue Irritants in Toothpaste: A Case Report

In this case, an adolescent patient presented with multiple, asymptomatic ulcerated lesions- resembling aphthous ulcerations- located in the oral cavity. The etiology of these lesions appeared to be associated with soft tissue irritants found in the patient's toothpaste. This report highlights the need to rule out known oral irritants in dentifrices for patients who present with oral ulcerations.

Glad to be sad, and other examples of benign masochism

AbstractWe provide systematic evidence for the range and importance of hedonic reversals as a major source of pleasure, and incorporate these findings into the theory of benign masochism. Twenty-nine different initially aversive activities are shown to produce pleasure (hedonic reversals) in substantial numbers of individuals from both college student and Mechanical Turk samples. Hedonic reversals group, by factor analysis, into sadness, oral irritation, fear, physical activity/exhaustion, pain, strong alcohol-related tastes, bitter tastes, and disgust. Liking for sad experiences (music, novels, movies, paintings) forms a coherent entity, and is related to enjoyment of crying in response to sad movies. For fear and oral irritation, individuals also enjoy the body’s defensive reactions. Enjoyment of sadness is higher in females across domains. We explain these findings in terms of benign masochism, enjoyment of negative bodily reactions and feelings in the context of feeling safe, or pleasure at “mind over body”. In accordance with benign masochism, for many people, the favored level of initially negative experiences is just below the level that cannot be tolerated.

Gustatory modulation of the responses of trigeminal subnucleus caudalis neurons to noxious stimulation of the tongue in rats

Certain tastants inhibit oral irritation by capsaicin, whereas anesthesia of the chorda tympani (CT) enhances oral capsaicin burn. We tested the hypothesis that tastants activate the CT to suppress responses of trigeminal subnucleus caudalis (Vc) neurons to noxious oral stimuli. In anesthetized rats, we recorded Vc unit responses to noxious electrical, chemical (pentanoic acid, 200μm) and thermal (55°C) stimulation of the tongue. Electrically evoked responses were significantly reduced by a tastant mix and individually applied NaCl, monosodium glutamate (MSG), and monopotassium glutamate. Sucrose, citric acid, quinine and water (control) had no effect. Pentanoic acid-evoked responses were similarly attenuated by NaCl and MSG, but not by other tastants. Responses to noxious heat were not affected by any tastant. Transection and/or anesthesia of the CT bilaterally affected neither Vc neuronal responses to electrical or pentanoic acid stimulation, nor the depressant effect of NaCl and MSG on electrically evoked responses. Calcium imaging showed that neither NaCl nor MSG directly excited any trigeminal ganglion cells or affected their responses to pentanoic acid. GABA also had no effect, arguing against peripheral effects of GABA, NaCl or MSG on lingual nocicepive nerve endings. The data also rule out a central mechanism, as the effects of NaCl and MSG were intact following CT transection. We speculate that the effect is mediated peripherally by the release from taste receptor cells (type III) of some mediator(s) other than GABA to indirectly inhibit trigeminal nociceptors. The results also indicate that the CT does not exert a tonic inhibitory effect on nociceptive Vc neurons.

Eugenol and carvacrol induce temporally desensitizing patterns of oral irritation and enhance innocuous warmth and noxious heat sensation on the tongue

Eugenol and carvacrol, from the spices clove and oregano, respectively, are agonists of TRPV3, which is implicated in transduction of warmth and possibly heat pain. We investigated the temporal dynamics of lingual irritation elicited by these agents, and their effects on innocuous warmth and heat pain, using a half-tongue method in human subjects. The irritant sensation elicited by both eugenol and carvacrol decreased across repeated applications at a 1-minute interstimulus interval (self-desensitization) which persisted for at least 10minutes. Both agents also cross-desensitized capsaicin-evoked irritation. Eugenol and carvacrol significantly increased the magnitude of perceived innocuous warmth (44°C) for >10minutes, and briefly (<5minutes) enhanced heat pain elicited by a 49°C stimulus. Similar albeit weaker effects were observed when thermal stimuli were applied after the tongue had been desensitized by repeated application of eugenol or carvacrol, indicating that the effect is not due solely to summation of chemoirritant and thermal sensations. Neither chemical affected sensations of innocuous cool or cold pain. A separate group of subjects was asked to subdivide eugenol and carvacrol irritancy into subqualities, the most frequently reported being numbing and warmth, with brief burning, stinging/pricking, and tingle, confirming an earlier study. Eugenol, but not carvacrol, reduced detection of low-threshold mechanical stimuli. Eugenol and carvacrol enhancement of innocuous warmth may involve sensitization of thermal gating of TRPV3 expressed in peripheral warm fibers. The brief heat hyperalgesia following eugenol may involve a TRPV3-mediated enhancement of thermal gating of TRPV1 expressed in lingual polymodal nociceptors.

Comparison of citalopram and other selective serotonin reuptake inhibitor ingestions in children

Context. In adults, citalopram is more likely to cause seizures and ECG changes than other selective serotonin reuptake inhibitors (SSRIs). Data in children are lacking, yet the 2007 American Association of Poison Control Centers out-of-hospital citalopram consensus guideline mirrors the guideline for other SSRIs. Objective. To compare the clinical effects and hazard index of citalopram with other SSRIs in pediatric ingestions. Methods. An 11-year retrospective analysis of national poison center data was conducted. Acute, known-type SSRI ingestions in children younger than 6 years with known outcome were included. Clinical effects and hazard index (number of major or fatal outcomes/1000 SSRI ingestions) were compared. Citalopram dose-response was evaluated. Results. The 35 296 included cases by SSRI type were citalopram (3747), escitalopram (4815), fluoxetine (5946), fluvoxamine (273), paroxetine (7157), and sertraline (13 358). The overall hazard index was 0.340. The hazard index for citalopram (0.801) was 2.8-fold higher than for non-citalopram SSRIs (0.285). Comparing seizures (single or multiple discrete) and cardiac effects (conduction disturbances, other ECG changes or other dysrhythmia) of citalopram with the other SSRIs, pediatric citalopram ingestions were more likely to develop seizures (5 of 3747 [0.13%] vs. 10 of 31 549 [0.03%], OR = 4.2; 1.4–12.3) and cardiac toxicity (9 of 3747 [0.24%] vs. 25 of 31 549 [0.08%], OR = 3.0; 1.4–6.5). Clinical effects occurring more frequently with other SSRIs included tachycardia (p = 0.0236), oral irritation (p = 0.0412), vomiting (p = 0.0036), agitation/irritability (p = 0.0104), and hyperthermia (p = 0.0314). There was a dose response only for single or multiple discrete seizures, mydriasis and clinically significant responses (a predetermined subset of CNS and cardiopulmonary clinical effects). Meaningful triage thresholds for citalopram could not be determined due to the low frequency of significant clinical effects. Conclusion. Children develop minimal toxicity with SSRI ingestions. Seizures and ECG changes, while uncommon, occur more frequently with citalopram. Doses associated with significant outcomes suggest that the triage guideline for citalopram does not need to be modified.

Effect of hydrophilic polymer on complexing efficiency of cyclodextrins towards efavirenz-characterization and thermodynamic parameters

The present work describes the effect of PVP on the complexation efficiency of cyclodextrins towards efavirenz, a poorly soluble antiretroviral agent imparting irritating sensation to buccal cavity. The phase solubility study indicates 1:1 stoichiometry for binary and ternary systems. DSC and XRPD revealed complete inclusion only in the lyophilized systems. The ternary systems were autoclaved before being lyophilized for the best results. Proton NMR suggests that the chlorobenzene part of benzoxazinone ring of the drug is involved in inclusion and was confirmed by 2D-COESY. The thermodynamic parameters, indicative of complexation efficiency were calculated calorimetrically by determining the interaction enthalpy of efavirenz with cyclodextrins in the presence and absence of PVP. The value of stability constants increased in the order β-CD < HP-β-CD < M-β-CD and is still higher in the presence of PVP illustrating the facilitation of the inclusion. Molar enthalpy of interaction of autoclaved solid formulation determined calorimetrically indicated stronger interaction for efavirenz:M-βCD-PVP system (−12.20 kJ/mol) which showed highest solubility and dissolution rate. The in vitro measurement of permeability showed a ten fold increase in the flux for the autoclaved formulation containing efavirenz-M-β-CD-PVP. In conclusion, encapsulation by cyclodextrins increases the solubility and suppresses the oral irritation of efavirenz. PVP further increases the complexation efficiency and decreases the bulk of cyclodextrins.

Synthesis and biological evaluation of PMMA/MMT nanocomposite as denture base material

Inorganic-polymer nanocomposites are of significant interest for emerging materials due to their improved properties and unique combination of properties. Poly (methylmethacrylate) (PMMA)/montmorillonite (MMT) nanocomposites were prepared by in situ suspension polymerization with dodecylamine used as MMT-modifier. X-ray diffraction (XRD) and transmission electron microscopy (TEM) were used to characterize the structures of the nanocomposites. Cytotoxicity test, hemolysis test, acute systemic toxicity test, oral mucous membrane irritation test, guinea-pig maximization test and mouse bone-marrow micronucleus test were used to evaluate the biocompatibility of PMMA/MMT nanocomposites. The results indicated that an exfoliated nanocomposite was achieved, and the resulting nanocomposites exhibited excellent biocompatibility as denture base material and had potential application in dental materials.

Unusual Pungency from Extra-Virgin Olive Oil Is Attributable to Restricted Spatial Expression of the Receptor of Oleocanthal

Oleocanthal, a major phenolic compound in extra-virgin olive oil with antiinflammatory properties, elicits an unusual oral pungency sensed almost exclusively in the throat. This contrasts with most other common oral irritants, such as cinnamaldehyde, capsaicin, and alcohol, which irritate mucus membranes throughout the oral cavity. Here, we show that this rare irritation pattern is a consequence of both the specificity of oleocanthal for a single sensory receptor and the anatomical restriction of this sensory receptor to the pharynx, within the oral cavity. We demonstrate, in vitro, that oleocanthal selectively activates the hTRPA1 channel in HEK 293 cells and that its ability to excite the trigeminal nervous system in rodents requires a functional TRPA1. Moreover, we similarly demonstrate that the over-the-counter analgesic, ibuprofen, which elicits the same restricted pharyngeal irritation as oleocanthal, also specifically excites rodent sensory neurons via TRPA1. Using human sensory psychophysical studies and immunohistochemical TRPA1 analyses of human oral and nasal tissues, we observe an overlap of the anatomical distribution of TRPA1 and the regions irritated by oleocanthal in humans. These results suggest that a TRPA1 (ANKTM1) gene product mediates the tissue sensitivity to oleocanthal within the oral cavity. Furthermore, we demonstrate that, despite the fact that oleocanthal possesses the classic electrophilic reactivity of many TRPA1 agonists, it does not use the previously identified activation mechanism via covalent cysteine modification. These findings provide an anatomical and molecular explanation for a distinct oral sensation that is elicited by oleocanthal and ibuprofen and that is commonly experienced around the world when consuming many extra-virgin olive oils.

High α-Defensin and S100A7 Expression and Missing DOC-1 Down-Regulation Characterize Irritation Fibromas of the Oral Cavity and May Counteract Malignant Transformation

The purposes of this study were to analyze the gene expression pattern of antimicrobial peptides, tumor suppressors, growth factors, matrix metalloproteases, and inflammatory cytokines and chemokines in oral irritation fibromas and to identify genes with protective effects against malignant transformation in benign proliferating tumors of the oral mucosa. Biopsies of irritation fibromas (n = 15) and healthy gingiva (n = 15) were obtained during routine surgical procedures. RNA was extracted according to standard protocols, and transcription levels of CCL20, DEFA 1/3, DEFA 4, S100A7, DOC-1, interleukin (IL) 1β, IL-6, IL-8, IL-10, tumor necrosis factor α, Cox-2, matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-8, MMP-9, transforming growth factor β1, transforming growth factor α, and keratinocyte growth factor were analyzed by real-time polymerase chain reaction. In addition, immunostaining was performed to visualize the transcription products of the genes of interest in fibroma tissue as well as in healthy gingiva. The gene expression of S100A7 was 11.3-fold and that of DEFA 1/3 was 14-fold higher in irritation fibromas than in healthy gingiva, whereas the expression of MMP-3 and of inflammation markers IL-1β, IL-6, IL-8, tumor necrosis factor α, and Cox-2 was reduced. Profound down-regulation of DOC-1 gene expression, characteristic for proliferating malignant tumors of the oral cavity, was in irritation fibromas not verifiable. Changes in the expression pattern of S100A7, DEFA 1/3, and MMP-3 seem to be involved in the development of irritation fibromas, whereas chronic inflammation might be of less importance. Overexpression of S100A7, but missing down-regulation of the tumor-suppressor gene DOC-1, might exert protective effects and counteract malignant transformation of benign, proliferating lesions of the oral cavity.

A New Type of Colored Alumina/Glass Composite Biological Safety Assessment - Oral Mucous Membrane Irritation and Skin Sensitivity Tests

Objective: to describe and demonstrate an oral mucosa irritation and a skin sensitivity test for evaluation of the biological safety of a colored alumina/glass composite (AGC). Methods: colored alumina/glass composite and control materials were sutured to mucine bilateral cheek pouch mucosa, in a position for gross observation and for histological and cytological examination; skin irritation activity of the composite was tested by intradermal injection of a guinea pig test solution, by inducing, enhancing, and stimulating the allergic response observed after local tissue exposure. Results: colored AGC in mouse cheek pouch mucosa stimulated the same reaction as the control, with no significant inflammatory reaction or infiltration of inflammatory cells. Guinea pigs showed no obvious erythema or edema from the irritation test, such that the assessment of colored AGC skin allergy response in mice was 0%. Conclusion: colored AGC was benign towards mouse oral mucosa and elicited no allergic skin inflammation response, indicating that in these aspects this material had good biological safety.

Self- and Cross-desensitization of Oral Irritation by Menthol and Cinnamaldehyde (CA) via Peripheral Interactions at Trigeminal Sensory Neurons

Menthol and cinnamaldehyde (CA) are plant-derived spices commonly used in oral hygiene products, chewing gum, and many other applications. However, little is known regarding their sensory interactions in the oral cavity. We used a human psychophysics approach to investigate the temporal dynamics of oral irritation elicited by sequential application of menthol and/or CA, and ratiometric calcium imaging methods to investigate activation of rat trigeminal ganglion (TG) cells by these agents. Irritancy decreased significantly with sequential oral application of menthol and CA (self-desensitization). Menthol cross-desensitized irritation elicited by CA, and vice versa, over a time course of at least 60 min. Seventeen and 19% of TG cells were activated by menthol and CA, respectively, with ∼50% responding to both. TG cells exhibited significant self-desensitization to menthol applied at a 5, but not 10, min interval. They also exhibited significant self-desensitization to CA at 400 but not 200 μM. Menthol cross-desensitized TG cell responses to CA. CA at a concentration of 400 but not 200 μM also cross-desensitized menthol-evoked responses. The results support the argument that the perceived reductions in oral irritancy and cross-interactions between menthol and CA and menthol observed (at least at short interstimulus intervals) can be largely accounted for by the properties of trigeminal sensory neurons innervating the tongue.

Diagnóstico Precoce, Tratamento Conservador e Remissão Completa de Osteorradionecrose de Mandíbula - Relato de Caso

IntroductionOsteoradionecrosis (ORN) is characterized as one of radiotherapy's late adverse effects which causes great suffering and compromises patient's quality of life. The classical treatments for ORN are the hyperbaric therapy and surgery (mandibulectomy), quite expensive procedures with controversial indication. Conversely, the effectiveness of conservative treatments, such as topical chlorhexidine mouthwashes, is not well established in the literature. ObjectiveTo report the clinical case and the results in the conservative treatment and control protocols of the ORN in mandible established in a public health service. Case reporta black 45-year-old female patient was treated for squamous cell carcinoma in the past 3 years. She underwent partial glossectomy and adjuvant radiotherapy (7500Cg) on primary tumor area and neck. Patient was referred with a painful condition exhibiting multiple areas of bone exposure of about 2.5cm in its longest axis. Three-times a day mouthwashes with aqueous chlorhexidine gluconate solution 0.12% was prescribed for an indefinite period associated with rigorous oral hygiene and elimination possible oral irritants. Clinical follow was performed weekly until early response and monthly after this period. Two weeks after initial treatment there was complete remission of prodromal symptoms, and after six months sequestrectomy treatment was indicated under antibiotic prophylaxis. Total mucosa covered the bone defect 4 weeks after surgery. Discussion and ConclusionThe treatment was effective. The institution of conservative therapy avoided the necessity of hyperbaric therapy or surgical resection block (mandibulectomy). The results offered less morbidity to the patient and rationalization of the public health resources.

Safety and toxicological evaluation of a novel chromium(III) dinicocysteinate complex

Chromium(III) is an essential trace element required for normal protein, fat and carbohydrate metabolism. It also helps in energy production and increasing lean body mass. Chromium(III) dinicocysteinate (CDNC) is a unique form of bioavailable chromium(III). This study was focused on determining the broad spectrum safety of CDNC. Acute oral, acute dermal, primary dermal and eye irritation studies, Ames’ bacterial reverse mutation assay, mammalian erythrocyte micronucleus test, and a 90-day dose-dependent oral toxicity study were conducted. Acute oral and dermal LD50 of CDNC was found to be greater than 2000 mg/kg in Sprague-Dawley rats. A primary skin irritation study in New Zealand Albino rabbits demonstrated CDNC as slightly irritating. An eye irritation study exhibited that CDNC is moderately irritating. Ames’ bacterial reverse mutation assay and mammalian erythrocyte micronucleus test demonstrated CDNC as non-mutagenic. A dose-dependent 90-day oral toxicity study demonstrated no significant toxicity of CDNC. Body weight, food and water consumption, selected organ weights (expressed as percentages of body or brain weights), ocular health, hematology, blood chemistry, and histopathology showed no abnormal changes. Clinical and histopathological evaluation of CDNC identified a dose level of 5.7 mg/kg/day as the no observed adverse effect level (NOAEL). Overall, these results demonstrate the broad spectrum safety of CDNC.

Acute, Multiple-Dose Dermal and Genetic Toxicity of Nu-3: A Novel Antimicrobial Agent

Nu-3 [butyl-phosphate-5′-thymidine-3′-phosphate-butyl] is a modified nucleotide that has been shown to have antimicrobial activity against a range of bacteria including Pseudomonas aeruginosa. However, data on the toxicological profile of Nu-3 are still lacking. In the present study, the toxicity of Nu-3 was evaluated by the following studies: acute oral toxicity, dermal and mucous membrane irritation, multiple-dose toxicity and genotoxicity in vivo and vitro. The acute oral toxicity test in mice showed that Nu-3 had an LD50 of 2001mg/kg body weight. The irritation tests on rats revealed that Nu-3 was not irritant, with an irritation scoring of 0. The multiple-dose toxicity study in rats showed that Nu-3 did not cause significant changes in histology, selected serum chemistry, and hematological parameters compared to the controls. Rats administrated with multiple-doses of Nu-3 showed no visible toxic symptoms. Both in vitro and in vivo, Nu-3 exhibited no notable genetic toxicity. Overall, the data suggest that Nu-3 is hypotoxic or nontoxic antimicrobial compound that warrants being further developed for treating Pseudomonas aeruginosa infection.