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Litron Laboratories Ltd

Address

3500 WINTON PL
ROCHESTER, NY, 14623-2860
USA

UEI: LJH7LE9AUHL5

Number of Employees: N/A

HUBZone Owned: No

Woman Owned: No

Socially and Economically Disadvantaged: No

SBIR/STTR Involvement

Year of first award: 1985

Phase I Awards

Phase II Awards

55.17%

Conversion Rate

$4,932,820

Phase I Dollars

$12,126,313

Phase II Dollars

$17,059,133

Total Awarded

Awards

Up to 10 of the most recent awards are being displayed. To view all of this company's awards, visit the Award Data search page.

Development of a Comprehensive Hen's Egg Model for Genotoxicity Testing

Amount: $295,734 Topic: R

Project Summary Pharmaceuticals and various industrial chemicals undergo comprehensive toxicological assessment in order to safeguard human health. Genetic toxicology is a key component of this risk assessment. This testing evaluates chemicals for their potential to damage DNA, an integral factor in the development of cancer and other diseases. For decades, in vivo assays have guided genotoxic risk assessment due to their ability to mirror physiological responses in humans. Their endogenous metabolism provides the enzymatic activation necessary for generating genotoxic intermediates, many of which are difficult to detect with in vitro assays. Additionally, their complete organ systems provide the structure for identifying organ specific genotoxicity, especially effects in liver and blood. Leading in vivo assays include the mammalian micronucleus assay, comet assay, chromosomal aberration assays, and rodent-based mutational assays. While these have served as a pillar of genotoxic risk assessment, regulatory agencies worldwide have begun to restrict and even eliminate the use of animals in toxicology research. This significant shift in risk assessment has left the field of genetic toxicology in need of a non-animal, metabolically-active systems that effectively models genotoxic risk in humans. In vitro assays provide initial insight into genotoxic risk, but many lack endogenous metabolic activation or only focus on individual cell types/organs. We will address the pressing need for an effective in vitro genotoxicity assay through our development of a comprehensive hen’s egg model for genotoxic analysis. The hen’s egg is a unique system in that it is not considered an animal model due to deficiencies in brain activity and pain perception early in development. Yet, similar to in vivo models, the hen’s egg has endogenous metabolic activity and functioning hepatic and hemopoietic organ systems. We will leverage these features to develop an assay that simultaneously evaluates genotoxicity in the blood and liver. Our utilization of flow cytometry and high content imaging will automate micronuclei quantification in the erythrocytes and hepatocytes. Furthermore, we will incorporate the assessment of genotoxic and cytotoxic biomarkers, providing valuable insight into organ specific toxicity and genotoxic mode of action. The development, optimization and validation of our hen’s egg genotoxicity assay will meet the critical need for an accurate, metabolically-active in vitro genotoxicity assay, while fulfilling upcoming regulatory requirements.

SBIR

Phase I

2024

HHS

NIH

Modeling the Responsiveness of Sensitive Populations to Genotoxic Agents Using DNA Repair Inhibitors

Amount: $230,278 Topic: R

Project Summary It is well recognized that conventional toxicology assays exhibit a crucial deficiency. Specifically, their use of limited numbers of cell lines and rodent strains does not provide information about toxic responses that may occur in sensitive human populations. Although studying very large numbers of cell lines and laboratory rodent models could theoretically address this issue, it is not a practical answer. There are simply too many legacy chemicals and new chemical substances being developed for this to represent a routine testing scheme. Fortunately, in the area of genetic toxicology, a solution exists. Our innovative approach takes into account the fact that inter-subject differences in sensitivity to genotoxic agents is predominately due to variable DNA repair capacity. Our project will develop an efficient, high throughput, in vitro genotoxicity assay platform that provides information about chemicals’ potential to cause DNA damage in prototypical and sensitive human populations. The high efficiency of our proposed approach is in part explained by our decision to study a single p53- competent human cell line (TK6) to generate prototypical genotoxic response profiles. Sensitive population responses will be modelled by co-exposing cells to each test chemical in combination with a panel of small molecule DNA repair inhibitors. These inhibitors will be chosen to cover each of the major DNA repair pathways. In addition to our use of DNA repair inhibitors to efficiently mimic sensitive populations, other innovative aspects of our project include our use of a multiplexed DNA damage assay to cover multiple biomarkers of genotoxicity and cytotoxicity, and state-of-the-art benchmark dose software to characterize the family of dose-response relationships that will be generated for each chemical studied. Once reduced to practice, we will make the assay available as a set of kit-formatted reagents, and also through fee-for-service testing.

SBIR

Phase I

2023

HHS

NIH

High Throughput Screen and High Information Follow-Up Tests for Genotoxicants

Amount: $1,627,653 Topic: R

Project SummaryCurrent batteries of genetic toxicology assays exhibit several critical deficiencies. First, the throughput capacity of in vitro genotoxicity tests is low, and does not meet current needs, especially for early, high volume screening environments that need to prioritize chemicals for further testing and/or development. Second, conventional assays provide simplistic binary calls, genotoxic or non-genotoxic. In this scheme there is little or no information provided about genotoxic mode of action. This is severely limiting, as it does not generate key information necessary for prioritizing chemicals for further testing, guiding subsequent assays’ endpoints/experimental designs, or conducting risk assessments. Finally, most current assays do not place requisite emphasis on dose response relationships, and therefore do not contextualize the results in terms of potency. These deficiencies prevent genotoxicity data from optimally contributing to modern risk assessments, where all of these capabilities and high information content are essential. We will solve these issues by developing, optimizing, and validating a two-tiered testing strategy based on multiplexed DNA damage responsive biomarkers and high-speed flow cytometric analysis. The first-tier focuses on throughput and is used to prioritize likely genotoxicants for more comprehensive analysis in second tier testing. Specifically, it involves a collection of several multiplexed biomarkers that will be used to identify likely genotoxic agents and provide a preliminary assessment of genotoxic mode of action. The gH2AX biomarker detects DNA double strand breaks, phospho-histone H3 identifies mitotic cells, nuclear p53 content reports on p53 activation in response to DNA damage, the frequency of 8n+ cells measure polyploidization, and the ratio of nuclei to microsphere counts provides information about treatment-related cytotoxicity. The second tier focuses on information content and considers many more concentrations as well as additional biomarkers, including micronucleus formation. Collectively, the tier two results provide definitive predictions about test chemicals’ genotoxic potential, mode of action, and potency. Over the course of this project we will study more than 3,000 diverse chemicals in order to understand the performance characteristics and generalizability of the two-tiered testing strategy. An interlaboratory trial will be conducted with prototype assay kits to assess the transferability of the methods, with the ultimate goal of providing the Nation with commercially available kits and testing services.

SBIR

Phase II

2022

HHS

NIH

High Throughput Screen and High Information Follow-Up Tests for Genotoxicants

Amount: $204,743 Topic: NIEHS

SBIR

Phase I

2021

HHS

NIH

Development of rat liver 3D organoid methods to address genotoxicity screening

Amount: $176,622 Topic: R

Project Summary Studying cells in simple 2D culture systems has many advantages with of ease of use, ability to screen many conditions in a short amount of time, targeted addition or deletion of genes, proteins or other components and focused study of specific pathways representing only a few. However, that simplicity can also lead to loss of key functions and an overall lack of relevancy to whole organisms, especially humans. In an effort to bridge this gap between cells in a dish and a human being, in vitro models are being developed that mimic the function of whole organs, so-called organotypic cultures. These models represent an opportunity to study highly complex, multicellular systems that will respond more like actual organs as opposed to cells grown in a simple monolayer. Our studies will develop a model of rat liver cells grown in a 3-dimensional format and pair that with an efficient, high-content analytical platform that will provide information on DNA function and cell health. The value of these types of models is significant for both basic science and more targeted research efforts such as human safety studies. Assessment of the safety of compounds like drug candidates, industrial chemicals and consumer products relies on preclinical test models to report useful information of human safety. The ability of cell-based models to do this is often challenged when the in vitro and in vivo systems lack sufficient relevancy to the human condition. The proposed 3D organ models may overcome existing limitations and result in lower costs while providing better information. The combination of data-rich assays that enable fast and efficient assessment of in vitro animal-derived organ models represents an opportunity to improve safety testing and create tools that will benefit numerous other research initiatives that rely on in vitro systems.Project Narrative Recent advances in cell culture have lead to the development of highly complex miniaturized tissue systems that replicate the function of human organs. The use of more relevant animal-derived organ models and the development of tools to better assess their responses could greatly improve chemical/drug safety studies, as well as aid in discoveries made in the basic sciences. This project seeks to create novel assays that can be used to provide quantitative information on activity and toxicological responses of complex 3D liver models to improve the relevancy and efficacy of these important in vitro organ systems.

SBIR

Phase I

2020

HHS

NIH

Next Generation Testing Strategies for Assessment of Genotoxicity

Amount: $956,962 Topic: 113

Project SummaryIt is well recognized that current batteries of genetic toxicology assays exhibit two critical deficiencies. First, the throughput capacity of in vitro mammalian cell genotoxicity tests is low, and does not meet current needs. Second, conventional assays provide simplistic binary calls, genotoxic or non-genotoxic. In this scheme there is little or no consideration for potency, and virtually no information is provided about molecular targets and mechanisms. These deficiencies in hazard characterization prevent genotoxicity data from optimally contributing to modern risk assessments, where this information is essential. We will address these major problems with current in vitro mammalian cell genetic toxicity assays by developing methods and associated commercial assay kits that dramatically enhance throughput capacity, and delineate genotoxicantsandapos; primary molecular targets, while simultaneously providing information about potency. Once biomarkers and a family of multiplexed assays have been developed for these purposes, an interlaboratory trial will be performed with prototype assay kits to assess the transferability of the methods.Project NarrativeDNA damage that cannot be faithfully repaired results in gene mutation and/or chromosomal aberrations, and these effects are known to contribute to cancer and other severe diseases. Thus, there is an important need for sensitive assays to evaluate chemicals for genotoxic and other deleterious effects. The work proposed herein will address issues that have plagued genotoxicity assessments for the last several decades: low throughput, lack of potency metrics, and little to no information about molecular targets. We will address these major problems with current genetic toxicity assays by developing new methods and associated commercial assay kits.

SBIR

Phase II

2019

HHS

NIH

Validation of Cross-Species Biomarkers of DNA Damage

Amount: $1,246,448 Topic: 113

Project Summary This project will validate two high throughput human blood based DNA damage assays and develop them into commercial kitsThe assays monitor types of damage associated with important human diseasesWhereas the PIG A assay reports on gene mutationthe micronucleated reticulocyteMN RETassay is responsive to chromosomal breaks and or lossesThe biomarkers are applicable to both humans and laboratory animals and will fulfill two important needsextension of findings in laboratory animal models to direct studies in humansand performance of well controlled mechanistic laboratory studies to understand observations first made in humansThe assays utilize immunomagnetic separation prior to flow cytometry to dramatically enrich the relevant cell populations and thereby enhance assay precision and sensitivityBy providing simple to use kits with thoroughly documented reproducibility and inter laboratory transferabilityand validating the biomarkers for specific usesresearchers will have available tools with unprecedented efficiencies for comprehensively studying those factors that contribute to inter individual differences in human DNA damageApplications include the study of drug treatmentshost and or life style factors that contribute to inter individual differences in DNA damage and repairexaggerated sensitivities to antineoplastic therapiesand population based epidemiology studies of environmental exposuresincluding occupational exposuresThe project benefits from a strong multidisciplinary team of internationally recognized scientists with a proven track record of successfully converting research advances into reliable commercial assay kits Project Narrative This project will validate two high throughput human blood based DNA damage assays and develop them into commercial kitsThe assays represent significant advances in the ability to directly monitor important types of DNA damage in humansand their cross species nature is ideal for supporting mechanistic laboratory studies when necessaryValidation work will include but is not limited to assessments of assay reproducibility within and among laboratoriesvalidation of target cellsand identification of physiological and lifestyle factors that affect assay resultsThe proposed work also includes the evaluation of several important use cases for these kitsfor example studying DNA damage resulting from chemotherapiesand also systemic inflammation

SBIR

Phase II

2018

HHS

NIH

Validation of Cross-Species Biomarkers of DNA Damage

Amount: $172,660 Topic: NIEHS

SBIR

Phase I

2018

HHS

NIH

Next Generation Testing Strategies for Assessment of Genotoxicity

Amount: $178,854 Topic: 113

Project SummaryIt is well recognized that current batteries of genetic toxicology assays exhibit two critical deficienciesFirstthe throughput capacity of in vitro mammalian cell genotoxicity tests is lowand does not meet current needsSecondconventional assays provide simplistic binary callsgenotoxic or non genotoxicIn this scheme there is little or no consideration for potencyand virtually no information is provided about molecular targets and mechanismsThese deficiencies in hazard characterization prevent genotoxicity data from optimally contributing to modern risk assessmentswhere this information is essentialWe will address these major problems with current in vitro mammalian cell genetic toxicity assays by developing methods and associated commercial assay kits that dramatically enhance throughput capacityand delineate genotoxicantsandaposprimary molecular targetswhile simultaneously providing information about potencyOnce biomarkers and a family of multiplexed assays have been developed for these purposesan interlaboratory trial will be performed with prototype assay kits to assess the transferability of the methods Project NarrativeDNA damage that cannot be faithfully repaired results in gene mutation and or chromosomal aberrationsand these effects are known to contribute to cancer and other severe diseasesThusthere is an important need for sensitive assays to evaluate chemicals for genotoxic and other deleterious effectsThe work proposed herein will address issues that have plagued genotoxicity assessments for the last several decadeslow throughputlack of potency metricsand little to no information about molecular targetsWe will address these major problems with current genetic toxicity assays by developing new methods and associated commercial assay kits

SBIR

Phase I

2018

HHS

NIH

Automation of a Liver Genotoxicity Assay

Amount: $960,113 Topic: NIEHS

DESCRIPTIONprovided by applicantAssessment of chemicalspotential to cause chromosomal damage is an established and important part of preclinical genotoxicity safety testing for many consumer productsindustrial chemicalsand all pharmaceutical agentsCurrently the mammalian erythrocyte micronucleus test is the most commonly employed assay for in vivo assessment of chromosomal damagebut this assay reports specifically on genotoxicity that occurs in the bone marrowIn order to obtain a more comprehensive understanding of potential genotoxicitytesting guidance s recommend evaluation of a second tissueThe liverthe site of metabolism and in many cases activation of genotoxicantsis usually regarded as the preferred second tissueEven sothere is a lack of efficient and effective tools for studying liver genotoxicityThe Comet assay and transgenic rodent mutation models can be employed to study the liverbut these assays suffer from methodological and cost issues that limit their utilityAnother important consideration is that these assays are not highly amenable to integration with on going toxicology studiesmeaning additional animals are required for the liver genotoxicity assessmentOne alternative approach is to examine liver hepatocytes for the formation of micronucleian established indicator of chromosomal damageHowever existing methods for examining liver micronuclei are still emerging and currently based on a multi step sample processing scheme followed by manual scoring by microscopyThis approach is subjective and laborintensiveand results in too few cells being scored for reliable enumeration of micronucleated hepatocytesa situation that diminishes the ability of the test to detect weakly genotoxic agentsWe will overcome these deficiencies by combining simplerapid tissue processing and staining with high speed flow cytometric analysis to greatly improve the execution of liver micronucleus scoringFurthermorewe will multiplex several cytotoxicity measurements into the liver micronucleus assaythereby providing information that we predict will be important for interpreting the genotoxicity resultsThe methodology will be reduced to practice in the form of commercially available kitsand will contribute to the reduction and refinement of animal testingas it will make it feasible to integrate a liver genotoxicity assay ito ongoing toxicology studiesOverallthis project will meet a critical need in the practice of genetic toxicology by improving chemical safety assessments in several meaningful ways

SBIR

Phase II

2017

HHS

NIH