Agrochemical Inhalation Toxicology Evaluations

Agrochemical Inhalation Toxicology Evaluations

Inhalation is the primary method of drug delivery to patients with lung or airway disease and is the primary route of accidental exposure during the manufacture, handling, or use of agrochemicals. Therefore, exposure to agrochemicals via inhalation poses some potential risk to human health. The preparation of solutions, application by dusting or spraying, post-application cleaning of equipment, and even the processing of agrochemicals are all opportunities for unintentional inhalation. Exposure risks are usually acute or subacute, but toxic effects can be acute or chronic, especially for the respiratory system. For these reasons, inhalation studies are an important component of toxicological studies in regulatory submissions for new agrochemical registrations, and are constantly being updated. At BOC Sciences, we have accumulated rich experience and expertise to successfully test the effects of inhaled compounds, delivering safety assessment of inhalation toxicology required for your agrochemical products.

Introduction of Inhalation Toxicology

Generally, inhalation toxicology studies are performed in vitro or in vivo to assess the potential toxicity of materials that are to be/or may be inhaled. In inhalation toxicology experiments, relevant cell cultures and/or animal testing systems are exposed to aerosolized/vaporized testing material on one or more occasions. Prior to the start of the exposure period, experts optimize the atmospheric environment to meet the necessary acceptance criteria to demonstrate that the target dose can be achieved and that the atmosphere is respirable.

Application of Inhalation Toxicology

• Determination of dose levels for other regulatory studies
• Human risk assessment
• Agrochemical labeling and packaging

Figure 1. Cell-based in vitro lung models for the study of inhalation toxicity. (Faber, S. C.; et al. 2018)

A comprehensive range of inhalation toxicology testing for your agrochemical

Standard suite of inhalation toxicology studies

OEOECD 403: Acute inhalation toxicity

OECD 433: Acute inhalation study (fixed concentration)

OECD 412: Inhalation toxicity study (subacute, 28-day)

OECD 413: Inhalation toxicity study (subchronic, 90-day)

Non-standard suite of inhalation toxicology studies

• Chronic toxicity and carcinogenicity studies

OECD 451: Carcinogenicity studies

OECD 452: Chronic toxicity studies

OECD 453: Combined chronic toxicity/carcinogenicity studies

• DART studies

OECD 414: Prenatal developmental toxicity study

OECD 443: Extended one-generation reproductive toxicity study (EOGRTS)

OECD 416: Two-generation reproduction toxicity

OECD 421: Reproduction/developmental toxicity screening test

OECD 422: Combined repeated dose toxicity study with the reproduction/developmental toxicity screening test

• Genotoxicity studies

OECD 474: Erythrocyte micronucleus test (in vivo mammalian)

OECD 489: Alkaline comet assay (in vivo mammalian)

Figure 2. Generation of specialized patient-specific cells for use in inhalation toxicity testing. (Faber, S. C.; et al. 2018)

Exposure atmosphere characterization

We can conduct the delivery of aerosols, vapors and gases by using a variety of nebulizers, nebulizers, dry powder generators, gas/vapor generators or pressurized metered dose inhalers (MEDI). Moreover, to support the extensive inhalation toxicology studies, we also offer micronization/airflow milling including particle size distribution (PSD) analysis and media milling.

Equipment and technology

• Exposure/administration suites
• Inhalation delivery in rodents and nonrodents
• Directed flow (flow-past) systems
• State-of-the-art technologies to generate powder, liquid, or vapor atmospheres
• Early stage inhalation toxicology evaluation with intratracheal aerosol delivery
• Oropharyngeal aspiration
• Intranasal administration using a repeat dosing pipette or nasal pump spray device
• For respiratory measurements, we provide Fleisch pneumotach and respiratory inductive plethysmography and head-out plethysmography.

Figure 3. The human exposure to microplastic through different routes. (Guo, J. J.; et al. 2020)

Features of Our Services

• We have rich experience in performing inhalation toxicity studies on a wide range of agrochemicals, including difficult-to-handle, unpredictable and hazardous materials and nanomaterials.
• BOC Sciences has a team of dedicated inhalation toxicologists, aerosol technicians and chemical analysts to provide inhalation toxicity testing and related services to effectively demonstrate the efficacy of these substances to support the global registration of your agrochemicals.
• Our studies range from acute to sub-chronic and chronic through to carcinogenic. We focus on unique inhalation toxicology endpoints analysis such as neonatal, reproductive, neurotoxicology, safety pharmacology.
• Our team is experienced in conducting radiolabeled aerosol disposition studies. And we offer a variety of physiological testings, including respiratory and cardiological assessments, bronchoalveolar lavage, and pharmacokinetic sampling.

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

• Faber, S. C.; et al. Through the Looking Glass: In Vitro Models for Inhalation Toxicology and Interindividual Variability in the Airway. Applied In Vitro Toxicology. 2018. 4(2): 115-128.
• Guo, J. J.; et al. Source, migration and toxicology of microplastics in soil. Environment international. 2020. 137: 105263.