Agrochemical Non-genotoxic Carcinogenicity Evaluations

Agrochemical Non-genotoxic Carcinogenicity Evaluations

Epidemiological studies support the idea that most human cancers are associated with chemicals present in the human environment. Chemicals are thought to cause cancer through genotoxic or non-genotoxic mechanisms. Carcinogens are a large group of substances, organic and inorganic, directly involved in carcinogenesis. Depending on their mode of action, they can be classified as genotoxic (GTX) or non-genotoxic (NGTX). Non-genotoxic carcinogens have multiple mechanisms of cancer induction, including receptor-mediated endocrine regulation, non-receptor mediated endocrine regulation, regenerative proliferation, oxidative stress, xenobiotic receptor activation, and peroxisome proliferation. Due to the diversity of mechanisms of action, the tissue specificity and lack of genotoxicity, the identification of non-genotoxic compounds for agricultural use has become a challenging task.

Figure 1. Structures of common agrochemicals and pharmaceuticals that interact with esterases. (Frank.; et al. 2011)

Agrochemical Carcinogenicity Testing

Agrochemical non-genotoxic carcinogenicity studies involve the exposure of rodents to your agrochemical product for up to two years. We collect extensive in-life, survival and histopathology data, and perform comprehensive statistical data analysis to evaluate tumor parameters and understand the human relevance of rodent toxicological findings.

• Our skilled scientists have recognized expertise in studying rodent toxicology and its relevance to humans. We can assess the actual hazards to humans by investigating the pathways that define cellular sensitivity to chemicals.
• We are committed to solving problems related to compound safety through our collaborative approach and cutting-edge expertise. Our expert teams will work with our clients to design state-of-the-art investigational studies to understand mechanisms of action (MOA), interpret the results and make reliable recommendations to guide you to success.

Transgenic Models

BOC Sciences evaluates the carcinogenic potential from data collected in a two-year rat bioassay and a short-term mouse study using the following transgenic models.

• Tg.rasH2 mouse for non-genotoxic compounds
• Tg.AC mouse for dermal drugs

Figure 2. Effects produced by a genotoxic agent. (David, L.; et al. 2018)

Human Relevance Toxicology Capabilities

• Evaluate the existing data sets
• Confirm the hypothesized mechanism of action
• Confirm the specificity of the nuclear receptors involved using a unique transgenic model
• Model the MOA in primary hepatocytes
• Perform human-relevant studies in primary human hepatocytes
• Analyze and interpret the data
• Provide technical support for data defense

BOC Sciences Advantages

• Highly specialized technical and analytical services for the worldwide registration and regulatory compliance of agrochemicals
• Robust analytical testing programs that span from research and product development through the production process to final product
• Relies on broad industrial experience, ensuring that all of our work meets the high standards expected by our clients
• Our regulatory experts, toxicology consultants, scientists and inspectors will ensure that you receive maximum levels of guidance, testing and inspection you need.

References

• Frank.; et al. Adverse health effects of environmental chemical agents through non-genotoxic mechanisms. Journal of Epidemiology & Community Health. 2011.
• David, L.; et al. Evidence of Some Natural Products with Antigenotoxic Effects. Part 2: Plants, Vegetables, and Natural Resin. Nutrients. 2018. 10(12). 1954.