Guidelines for Writing Toxicology Reports for GRAS Certification Files: Data Requirements and Selection of Test Standards

2025,08,29

In the drafting of the GRAS certification dotes in the United States, the toxicology section is the core of the core, directly determining the safety conclusion of the declared substance under its intended use.

Writing a toxicology report not only requires a solid scientific foundation but also a profound understanding of regulatory requirements and assessment principles. Ruiou Technology has summarized the key points to note for enterprises' reference:

The overall principles of toxicology reports

1. Comprehensiveness and relevance

The report should comprehensively cover the toxicological data related to the declared substance, including toxicity information of itself, structural analogues or metabolites. The data must be relevant to the intended use of the substance, the route of exposure and the population.

2. Scientific rigor and clear reasoning

All cited research data must be sourced from reliable, peer-reviewed scientific literature or experimental reports that comply with Good Laboratory Practice (GLP). The data should be repeatable and interpretable. Toxicological data are not simply listed but require systematic analysis and argumentation to ultimately reach a clear safety conclusion.

3. Transparency and traceability

List all data sources in detail, including literature citations, experimental report numbers, etc., to ensure the transparency and traceability of the information.

Interpretation and application of toxicological data

1. Determination of NOAEL/LOAEL

Based on the results of toxicological studies, determine the dose at which no adverse effects were observed (NOAEL) or the lowest dose at which adverse effects were observed (LOAEL) at this dose. Select the species most sensitive to toxic effects and the most sensitive endpoint indicator NOAEL as the starting point for safety assessment.

2. Application of safety factors

The safety factor is a dimensionless ratio. On the basis of the NOAEL, an appropriate safety factor is applied to derive the acceptable daily intake (ADI) or safe intake. A safety factor greater than 100 is generally considered acceptable. This 100-fold safety factor is an empirical rule that has long been formed in the field of toxicology and is also known as the "uncertainty factor". It is usually obtained by multiplying two tenfold coefficients:

10 times: Used to make up for the differences between species (physiological differences between animals and humans).

10 times: Used to compensate for individual differences (the sensitivity differences among different individuals in a population).

In addition, commonly used safety factors also include: extrapolation from sub-chronic studies to chronic exposure (if chronic studies are lacking), and when using a LOAEL instead of a NOAEL (typically 10 times). The selection of safety factors should be based on sufficient scientific grounds and explanations.

3. Comparison with dietary exposure

Compare the derived safe intake with the estimated intake (EDI) in the dietary exposure assessment. If EDI is far below the safe intake, it can be concluded that the substance is safe for its intended use.

4. Comprehensive safety conclusion

After integrating all toxicological data, metabolic information and exposure assessment results, a clear safety conclusion was drawn. The conclusion should be concise and clear, and point out any potential risks or areas that require further attention.

Should key toxicological tests conducted by enterprises themselves comply with GLP and OECD standards?

The core of GRAS in the United States lies in "recognition" rather than mandatory regulatory requirements. Therefore, although the US FDA does not have a hard and fast rule that GRAS toxicology tests must follow GLP or OECD standards, in practice they are highly recommended and almost indispensable.

GLP is a strict quality management system designed to ensure that the planning, implementation, monitoring, documentation, reporting and archiving of non-clinical safety studies (such as toxicological tests) are highly reliable, complete and trustworthy. A study that does not follow the GLP standard may be questioned for reasons such as the lack of a detailed experimental protocol leading to an unrigorous method, the failure to properly record and preserve the original data resulting in incomplete data, and the absence of an independent quality assurance department for supervision leading to untrustworthy conclusions.

The OECD's "Guidelines for Chemical Testing" is a set of internationally recognized standardized test methods for assessing the impact of chemicals on human health and the environment. The OECD guidelines represent the highest international standards for toxicology research. Their experimental designs, animal numbers, observation indicators, data analysis methods, etc. have all undergone rigorous scientific verification. Research conducted in accordance with OECD guidelines can ensure the scientific rigor and comparability of the trial results, and the data is mutually acceptable among all OECD member countries, significantly reducing the cost and time of repetitive trials.

Traditional Wife Cake Box, Traditional Wife Cake, Chinese Pastry

Author:

Mr. funeng

E-mail:

254547278@qq.com

Phone/WhatsApp:

15268656188