Mechanisms of toxicity

Yersinia pestis

​The gram-negative pathogen Yersinia pestis is the causative agent of plague, a disease that has caused millions of deaths in three world pandemics. Plague still persists in Africa, Asia and the Americas and it is categorized as a re-emerging disease. The most prevalent form of the disease in nature is bubonic plague, which develops following transmission of the pathogen from rodent reservoirs to humans via infected fleas.

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Bacillus anthracis

​Bacillus anthracis, the ethological cause of Anthrax, is a spore- forming gram positive bacteria. Our group has mastered multiple clinical and laboratory microbiology techniques, from classical isolation and plating and selective growth in complicated media, to light microscopy, confocal and scanning (SEM) or transmission electron microscopy (TEM).

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Francisella tularensis

Francisella tularensis, the causative agent of tularemia, is a gram-negative facultative intracellular bacterium that can cause a life-threatening infection in humans. Depending on the site of infection, tularemia has several characteristic clinical variants. Of these, the respiratory route of infection is the most severe, causing a deadly disease upon exposure to a very low inhalation dose (as few as 1–10 bacteria).

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​Development of advanced laboratory techniques and tools for the isolation and propagation of various pathogenic viruses.Clinical and environmental diagnosis of viruses – isolation and identification using advanced techniques such as Transmission Electron Microscopy (TEM), genetic and immune-based diagnosis.

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Microbial toxins (botulinum)

Botulinum neutotoxins (BoNTs) are produced by the anaerobic bacterium Clostridium botulinum and are the most poisonous substances known in nature. Following entry into the circulation, BoNTs block neuro-transmission across neuromuscular junctions leading to systemic flaccid paralysis that may lead to respiratory failure and death.  

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Plant derived toxins (ricin, abrin)

Ricin and abrin are potent plant-derived lethal toxins that halt protein synthesis in cells. Pulmonary or systemic exposure to these toxins induces ARDS (acute respiratory stress syndrome) and multi-organ failure, respectively, leading inevitably to death.

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Inhalation toxicology

The inhalation laboratory includes state-of-the-art exposure systems especially designed and built for safe exposure to precise concentrations of various toxicants. 

  • Head only inhalation while animals are in a plethysmograph monitoring respiratory parameters.

  • Whole-body exposure of freely-moving rodents simulating real scenario exposure.

  • Acute and prolonged (chronic) exposure to different concentrations of toxicants.

  • Long term and repeated follow up of clinical evaluations, blood sampling, body weight and physiological measurements (whole body plethysmography, pulse oximetry, ECG, EEG, blood pressure, blood gas analysis, biochemistry of body fluids and tissues: cytokines, chemokines and PGE2) 

  • Evaluation of tissue damage: histology, histochemistry and immunohistochemistry.

  • Behavioral and cognitive evaluation.​​

  • Evaluation of therapeutic measures (e.g. aerosol or intramuscular).

Immunofluorescence labeling of neurons and glial populations in the rat brain

Immunofluorescence labeling of neurons and glial populations in the rat brain 

Neurological insult following systemic intoxication

Immediate and long-term brain damage induced by nerve agents and other toxic compounds. Evaluation of pharmacological prophylactic or post-exposure treatments aimed at elimination or minimization of brain pathology.

  • Biochemical and molecular analysis of neuronal enzyme activity, inflammatory markers in neurons and glia, cytokines and more.

  • Evaluation of tissue damage through histology, histochemistry and immune-histochemistry (see: Histology and Pathology).

  • Continuous tethered electroencephalography (EEG) and telemetry

  • Microdialysis of neurotransmitters

  • Behavioral tests

  • Receptor density (Bmax) and affinity (KD) evaluation.

Electrocardiogram and blood pressure evaluation in rodents
Electrocardiogram and blood pressure evaluation in rodents ​

Cardiovascular research

  • Invasive blood pressure and pulse monitoring in anesthetized animals.

  • Noninvasive cardiac output measurements.

  • Tethered and telemetry ECG in rats, pigs and mice. 

  • In-vivo animal models for toxicological exposure.​

Ocular​ surface insults​​

The eyes are among the main organs affected following irritant or vesicant exposure. Based on the similarities between rabbit and human corneas, ​we use our in vivo vapor exposure system in rabbits to study different aspects of ocular injury induced by vesicants, such as sulfur mustard, and other irritant compounds, with the aim of finding therapeutic measures. We use a slit lamp microscope and our semi-quantitative clinical severity score to continuously follow the dynamic course of the ocular injury and the pathological healing processes. Additional non-invasive monitoring includes pachymetry, specular microscopy, impression cytology and tear fluid collection. Histology, immunohistochemistry, biochemistry and mole​cular biology methods are applied to the ocular surface tissues at various time points post-exposure.​


Dachir S., Cohen M., Gurman H., Cohen L., Buch H. and Kadar T. Acute and long-term ocular effects of acrolein vapor on the eyes and potential therapies. Cutan. Ocul. Toxicol. 2015:34(4):286-293.​​

Kadar T., Dachir S., Horwitz V. and Amir A. Delayed development of limbal stem cell deficiency following chemical injury – pathogenesis and therapeutic strategies. US Ophthalmic Review. 2013;6:101-104.​

Ocular​ surface insults

Visual deficit

Nerve agent exposure at low concentrations, such as from residual vapor in the field, clothes, equipment or as a result of carry-through, can induce a reduction in pupil diameter (miosis) restricting the amount of light reaching the retina and causing dim vision, reduction in visual field and light reflex impairment due to desensitization of muscarinic receptors in the iris.

The outcome of theses ocular changes may affect the visual acuity and disrupt the ability to perform routine tasks. These ocular symptoms may occur unexpectedly and may persist for days and even weeks. In our lab, we focus on exploring the mechanisms involved in visual impairment following ocular exposure, and are highly motivated to develop optimized treatments which may enable rapid alleviation of visual impairment. ​

Histological section from hairless guinea-pig skin biopsies taken 24hr following exposure to sulfur mustard vapor. Typical vesic

Histological section from hairless guinea-pig skin biopsies taken 24hr following exposure to sulfur mustard vapor. Typical vesication, epithelial damage and hemorrhage in the dermis are seen. H&E staining, objective magnification x2​0.

Dermal research

Dermal research includes investigation of the mechanisms and potential treatments for skin damage induced by exposure to different toxicants and the development and evaluation of potential protective and decontaminating compounds.

  • Dermal exposure of small and large animals​ to liquid or vapor toxicants, that cause cutaneous insults and/or systemic effects.
  • Evaluation of dermal lesions by employing colorimetric and trans-epidermal water-loss measurements in addition to measurement of wound area.
  • Evaluation of wound-healing processes through detection of biochemical and inflammatory changes using histology, histochemistry and immunohistochemistry as w​ell as biochemical and molecular biology methods.
  • Development of therapeutic measures, decontamination and protective solutions (such as Dermostyx) following acute and long-term exposure to different toxicants. 
  • Draize tests for irritation. 
  • Ex vivo studies ​of enzymatic and diffusion assays using Franz cells.

​Developm​​ent of an animal model of intoxication

The department of Pharmacology develops unique animal models of intoxication, according to specific requirements suitable for various scenarios. The models enable research of intoxication mechanisms following exposure to a wide range of toxicants from liquids through gases, aerosols and powders using parenteral, inhalation o​r topical exposure method​s. ​​

A chamber for whole body exposure​
A chamber for whole body ​exposure