Replication and enhanced analysis of the FDA-iRISK comparative risk assessment model: A computational case study in R software

Kshitij Shrestha, Rojeena Shrestha

Department of Food Technology and Quality Control, Babarmahal, Kathmandu, Nepal

Highlights

• FDA-iRISK model successfully replicated in R, validating its computational engine.

• R-based estimates closely aligned with original Salmonella DALY results.

• Contamination reduction and improved cooling lowered risk by 93% and 99.9%.

• Uncertainty analysis revealed 7-fold variation in Listeria risk estimates.

• Open-source R framework offers flexible, reproducible food safety assessment.

 Abstract

This study successfully replicated the FDA-iRISK comparative food safety risk assessment model described by Chen et al. (2013) within the R software environment, validating its core computational engine for case studies on Salmonella in peanut butter and Listeria monocytogenes in soft cheese and cantaloupe. Our R-based model, which leverages Monte Carlo simulation, produced results strongly aligned with the original publication; for instance, it estimated 63.05 annual Disability-Adjusted Life Years (DALYs) for Salmonella, compared to the published 63.5 in the original manuscript. The model quantified the profound effectiveness of interventions, demonstrating a 93% risk reduction from a 2-log decrease in initial contamination and a 99.9% reduction from improved refrigeration control. Furthermore, we extended the model's utility through enhanced visualizations and a dedicated uncertainty analysis. This analysis revealed a 7-fold variation in risk estimates for Listeria, providing deeper insights into risk variability, intervention impacts, and the critical influence of parameter uncertainty. The outcome of this work is a transparent and flexible platform for robust food safety decision-making.

The Article was published in the following Journal

Food Control

Volume 192, February 2027, 112513

https://doi.org/10.1016/j.foodcont.2026.112513

 

Full Article is available in the link below:

https://authors.elsevier.com/a/1nZkY_LmCu-AVk

Proposed Regulatory Framework for Aloe Vera Beverages and Food Supplements

-Kshitij Shrestha, SFRO, DFTQC

Abstract

The safety of Aloe vera (L.) Burm. f. preparations in food and beverages remains scientifically contentious due to hydroxyanthracene derivatives (HADs), including aloin A, aloin B, aloe-emodin, emodin, and chrysophanol. The European Food Safety Authority (EFSA) concluded in 2018 that HADs should be considered genotoxic and carcinogenic unless specific data to the contrary exist, and was unable to establish a tolerable daily intake (Younes et al., 2018). In November 2024, the General Court of the European Union annulled Commission Regulation (EU) 2021/468, which had prohibited Aloe species preparations containing HADs (General Court of the European Union, 2024). Critically, however, the European Commission appealed this judgment in January 2025, and the case remains pending before the Court of Justice (European Commission, 2025). This manuscript provides a comprehensive technical analysis of the chemistry, toxicology, exposure assessment, and risk characterization for both Aloe vera juice products and food supplements. Physiologically based kinetic (PBK) modeling-facilitated quantitative in vitro to in vivo extrapolation (QIVIVE) has yielded predicted BMDL₁₀ values for aloe-emodin, enabling Margin of Exposure (MOE)-based risk characterization (Ren et al., 2024). Cancer risk estimates for non-decolorized whole-leaf extracts range from 7.4×10⁻⁴ (1 mg/kg-day) to 4.7×10⁻² (63.8 mg/kg-day) (Boudreau et al., 2013; National Toxicology Program, 2013). Purified preparations with HAD content below 10 ppm show no genotoxicity in validated test systems, with a NOAEL exceeding 1,845 mg/kg bw/day (Shao et al., 2013). A 2024 LC-MS/MS study of commercial Aloe vera beverages found considerable variability in aloin concentrations, yet the tested products did not show mutagenicity in the reported Ames experiments (Di Minno et al., 2024). We propose a risk-based regulatory framework incorporating product-specific HAD quantification, refined exposure assessment, and a tiered permissible limit system based on consumption patterns, while acknowledging that the European regulatory landscape remains in flux pending the outcome of the pending appeal.

Keywords: Aloe vera, hydroxyanthracene derivatives, genotoxicity, benchmark dose, margin of exposure, physiologically based kinetic modeling, risk assessment, food regulation

1. Introduction

Aloe vera (Aloe barbadensis Miller), a member of the Asphodelaceae family, has been utilized for centuries in traditional medicine systems and has gained considerable popularity in contemporary food supplements and beverages (Jangra et al., 2022). The global market for Aloe products in foods and cosmetics is currently valued at approximately US$ 1.6 billion, which is estimated to double by 2026 (Baldi et al., 2021). The plant is marketed for purported digestive health, immunomodulatory, and antioxidant benefits. However, the safety of oral consumption has been a persistent regulatory concern due to the presence of naturally occurring hydroxyanthracene derivatives (HADs), particularly aloin (a mixture of aloin A and B), aloe-emodin, emodin, and chrysophanol (Younes et al., 2018).