Application of the threshold of toxicological concern (TTC) concept to the safety assessment of chemically complex food matrices

The toxicological assessment of chemically complex food matrices (CCFM) usually is very time consuming, expensive and uses many animal studies. Improvements to obtain a more efficient assessment process remain limited as long as we retain traditional approaches to toxicological risk assessment. New concepts would be needed to achieve real...

Derivation of the minimal magnitude of the Critical Effect Size for continuous toxicological parameters from within-animal variation in control group data

Assuming that temporal fluctuations in physiological parameters (e.g. haematology, biochemistry) in individual healthy non-exposed animals are non-adverse, the minimal magnitude of the Critical Effect Size (CES) for a number of continuous parameters of toxicity studies was derived. A total of 36 studies (19 pharmaceutical preclinical studies in...

Risk assessment and food allergy: The probabilistic model applied to allergens

In order to assess the risk of unintended exposure to food allergens, traditional deterministic risk assessment is usually applied, leading to inconsequential conclusions as 'an allergic reaction cannot be excluded'. TNO therefore developed a quantitative risk assessment model for allergens based on probabilistic techniques resulting in a more...

Within-animal variation as a minimal critical effect size for continuous toxicological parameters applicable in the Benchmark dose approach (Extended Abstract)

Within-animal variation as an indication of the minimal magnitude of the critical effect size for continuous toxicological parameters applicable in the benchmark dose approach

In this study, the within-animal variation in routinely studied continuous toxicological parameters was estimated from temporal fluctuations in individual healthy nonexposed animals. Assuming that these fluctuations are nonadverse, this within-animal variation may be indicative of the minimal magnitude of the critical effect size (CES). The CES...

Inhaled formaldehyde: Evaluation of sensory irritation in relation to carcinogenicity

Objectives: The critical health effects of formaldehyde exposure include sensory irritation and the potential to induce tumours in the upper respiratory tract. In literature, a concentration as low as 0.24 ppm has been reported to be irritating to the respiratory tract in humans. Nasal tumour-inducing levels in experimental animals seem to be 1...

Oral-to-inhalation route extrapolation in occupational health risk assessment: A critical assessment

Due to a lack of route-specific toxicity data, the health risks resulting from occupational exposure are frequently assessed by route-to-route (RtR) extrapolation based on oral toxicity data. Insight into the conditions for and the uncertainties connected with the application of RtR extrapolation has not been clearly described in a systematic...

Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

Health risks resulting from occupational exposure to chemicals are controlled by the establishment of acceptable dermal and respiratory exposure levels. Due to a lack of route-specific toxicity data, acceptable levels are frequently established by means of route-to-route extrapolation. A pitfall in route-to-route extrapolation is the occurrence...

Data-base derived values for the interspecies extrapolation: A quantitative analysis of historical toxicity data

Critical effect sizes in toxicological risk assessment: A comprehensive and critical evaluation

A key issue in toxicological risk assessment is determining the effect level below which there is no reason for concern. In the Benchmark approach, this breaking point between adverse and non-adverse is called the critical effect size (CES). This study aimed to investigate the possibilities to determine CESs for toxicological effect parameters...