Regulatory & scientific support

A regulatory toxicologist evaluates scientific data to determine whether a substance or product can be used safely under defined exposure conditions and regulatory requirements. Regulatory toxicologists assess hazards, evaluate human exposure, establish health-based limits, prepare scientific documentation, and support regulatory decision-making throughout product development and approval processes.

Agirad provides independent regulatory toxicology and human health risk assessment services for pharmaceutical, veterinary pharmaceutical, medical device, chemical, food, feed, and cosmetics industries.

Toxicological assessments include:

• Toxicological risk assessments (TRA) and human health risk assessments
• Pharmaceutical impurity assessments, including genotoxic impurities and nitrosamines
• Extractables and leachables toxicological evaluations for medical devices
• Health-Based Exposure Limit (HBEL) and Permitted Daily Exposure (PDE) derivation
• Occupational Exposure Limit (OEL) and Occupational Exposure Band (OEB) assessments
• DNEL and DMEL derivation for chemical safety assessments
• REACH human health assessments and toxicology support
• Scientific evaluations, weight-of-evidence assessments, and regulatory documentation support

Each assessment is tailored to the product type, intended use, exposure scenario, available scientific evidence, and applicable regulatory requirements.

A toxicological risk assessment (TRA) is a scientific process used to determine whether exposure to a chemical substance could pose a risk to human health under specific conditions of use. It combines information on the toxicological properties of a substance and the expected level of exposure to determine whether potential risks are acceptable.

The assessment is based on four core components:

• Hazard identification: identification of the potential adverse effects associated with a substance.
• Hazard characterization: evaluation of the dose-response relationships, including the identification of critical effects and a point of departure, and application of appropriate uncertainty factors to derive health-based guidance values.
• Exposure assessment: estimation of the magnitude, frequency, duration and route of human exposure.

• Risk characterization: ontegration of hazard and exposure information to determine the overall level of risk and support scientifically justified safety conclusions.

The outcome of a TRA is a scientifically justified conclusion on whether the identified risk is acceptable under defined conditions of use. If uncertainties remain or risks are not adequately controlled, additional data generation, risk management measures, or use restrictions may be required to achieve regulatory acceptability.

A toxicological risk assessment is required whenever the safety of a chemical substance, material, or product must be demonstrated for human exposure.

TRAs are routinely prepared to support:

• Regulatory submissions
• Product safety evaluations
• Market authorization applications
• Regulatory compliance
• Product development
• Material selection
• Manufacturing changes
• Investigation of potential safety concerns

They are widely used across industries including:

• Medical devices
• Pharmaceuticals
• Chemicals (including REACH registrations)
• Cosmetics and personal care products
• Food and feed
• Food-contact materials
• Consumer products

A toxicological risk assessment may also be necessary when introducing a new substance, modifying a formulation, changing manufacturing processes, or when existing safety data are insufficient to demonstrate safe use.

A toxicological risk assessment is relevant for any organization that develops, manufactures, imports, or markets products that may result in human exposure to chemical substances.

Typical users include:

• Medical device manufacturers
• Pharmaceutical companies
• Chemical manufacturers
• Cosmetic and personal care companies
• Food and feed producers
• Packaging manufacturers
• Consumer product manufacturers
• Regulatory affairs professionals
• Product safety and toxicology teams

The scope of the assessment depends on several factors, including the substance involved, the intended use, expected exposure, target population, and applicable regulatory requirements.

A well-prepared toxicological risk assessment helps organizations demonstrate product safety, support regulatory submissions, and reduce compliance risks.

A toxicological risk assessment (TRA) relies on high-quality scientific data to evaluate whether human exposure to a substance is safe under its intended conditions of use. The amount and type of information required depend on the substance, exposure scenario, regulatory framework, and available evidence.

A comprehensive toxicological risk assessment typically includes:

• Toxicological data, including in vivo, in vitro, and in silico information
• Dose–response data and identification of relevant points of departure (e.g., NOAEL, LOAEL, or Benchmark Dose (BMD))
• Physicochemical properties that may influence absorption, distribution, metabolism, and elimination (ADME)
• Exposure assessment, including the route, frequency, duration, and estimated level of human exposure
• Existing regulatory evaluations and authoritative scientific opinions
• Peer-reviewed scientific literature
• Human data, including epidemiological studies or clinical evidence where available.

The strength of a toxicological risk assessment depends on the quality, relevance, and completeness of the available evidence. When data are limited, scientifically accepted approaches such as read-across, weight-of-evidence evaluations, and computational toxicology can often be used to support a robust safety assessment.

Regulatory submissions require clear, scientifically justified toxicological information that meets the expectations of regulatory authorities. Agirad supports organisations by preparing, reviewing, and strengthening toxicology documentation throughout the regulatory process.

Support includes:

• Preparation and review of toxicology sections for regulatory dossiers
• Non-clinical expert reports and scientific summaries
• Evaluation and justification of impurities, exposure limits, and safety assessments
• Weight-of-evidence evaluations and scientific argumentation
• Review of regulatory authority questions and identification of underlying toxicological concerns
• Preparation of scientifically justified responses and supporting documentation

By combining regulatory toxicology expertise with an understanding of applicable guidelines and scientific principles, Agirad helps organisations communicate complex safety information clearly, address regulatory questions effectively, and support informed regulatory decision-making.

Read-across and (Q)SAR approaches are scientific methods used to support toxicological assessments when experimental data are limited or when additional evidence is needed to evaluate safety.

Read-across uses toxicological information from similar substances to predict potential effects of a target substance, based on similarities in chemical structure, properties, or biological activity.

(Q)SAR (Quantitative Structure–Activity Relationship) models use relationships between chemical structure and biological activity to predict specific toxicological properties.

These approaches can support:

• Hazard assessment and characterisation
• Identification of data gaps
• Weight-of-evidence evaluations
• Regulatory submissions
• Reduction of unnecessary animal testing

When scientifically justified, read-across and (Q)SAR approaches provide valuable evidence for regulatory toxicology assessments. Their reliability depends on appropriate data selection, model applicability, and transparent evaluation of uncertainties.

A regulatory toxicology consultant should have a strong scientific background in toxicology, experience performing human health risk assessments, and knowledge of relevant regulatory frameworks.

Key qualifications include:

• Academic training in toxicology or a related scientific discipline
• Experience evaluating toxicological data and preparing risk assessments
• Knowledge of international guidelines and regulatory requirements
• Experience supporting regulatory submissions and scientific justifications

Professional recognition, such as Eurotox Registered Toxicologist (ERT) or Diplomate of the American Board of Toxicology (DABT), provides additional evidence of toxicology expertise and professional competence.

A qualified regulatory toxicologist combines scientific knowledge with regulatory experience to develop transparent, scientifically justified assessments that support product safety and regulatory decision-making.

Not all toxicological questions can be addressed through standard assessment pathways. Agirad provides independent scientific support for complex safety questions that require expert judgement, interpretation of available evidence, and development of scientifically justified regulatory strategies.

Support includes:

• Development of tailored toxicological and regulatory strategies
• Evaluation and interpretation of complex scientific data
• Weight-of-evidence assessments
• Literature reviews and state-of-the-art evaluations
• Assessment of data gaps and scientific uncertainties
• Application of approaches such as read-across, (Q)SAR, NAMs, and IATA where appropriate
• Preparation of expert reports, scientific justifications, and regulatory arguments
• Support during regulatory review and interactions with authorities

By integrating toxicological expertise, regulatory knowledge, and evidence-based approaches, Agirad helps organisations address challenging safety questions, reduce uncertainty, and develop clear, scientifically defensible conclusions.