Second Edition - Guidance Document on Integrated Approaches to Testing and Assessment (IATA) for Serious Eye Damage and Eye Irritation

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doi:10.1787/84b83321-en

Cited by 3 publications

(1 citation statement)

References 66 publications

(120 reference statements)

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“…Conversely, active substances had mean pH values that were on average farther from neutral pH. These results suggest that many of these chemicals may cause damage to ocular tissues at least in part via direct acidic or basic action, which is consistent with Guidance Document 263 that suggests that substances with pH extremes (i.e., ≤2 or ≥11.5) may be assumed to be corrosive, and no additional animal testing is needed . Similar results were observed for the GHS classification system.…”

Section: Results and Discussionmentioning

confidence: 99%

Mixtures-Inclusive In Silico Models of Ocular Toxicity Based on United States and International Hazard Categories

Sedykh¹,

Choksi

Allen

et al. 2022

Chem. Res. Toxicol.

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Computational modeling grounded in reliable experimental data can help design effective non-animal approaches to predict the eye irritation and corrosion potential of chemicals. The National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) has compiled and curated a database of in vivo eye irritation studies from the scientific literature and from stakeholder-provided data. The database contains 810 annotated records of 593 unique substances, including mixtures, categorized according to UN GHS and US EPA hazard classifications. This study reports a set of in silico models to predict EPA and GHS hazard classifications for chemicals and mixtures, accounting for purity by setting thresholds of 100% and 10% concentration. We used two approaches to predict classification of mixtures: conventional and mixture-based. Conventional models evaluated substances based on the chemical structure of its major component. These models achieved balanced accuracy in the range of 68–80% and 87–96% for the 100% and 10% test concentration thresholds, respectively. Mixture-based models, which accounted for all known components in the substance by weighted feature averaging, showed similar or slightly higher accuracy of 72–79% and 89–94% for the respective thresholds. We also noted a strong trend between the pH feature metric calculated for each substance and its activity. Across all the models, the calculated pH of inactive substances was within one log10 unit of neutral pH, on average, while for active substances, pH varied from neutral by at least 2 log10 units. This pH dependency is especially important for complex mixtures. Additional evaluation on an external test set of 673 substances obtained from ECHA dossiers achieved balanced accuracies of 64–71%, which suggests that these models can be useful in screening compounds for ocular irritation potential. Negative predictive value was particularly high and indicates the potential application of these models in a bottom-up approach to identify nonirritant substances.

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Section: Results and Discussionmentioning

confidence: 99%

Mixtures-Inclusive In Silico Models of Ocular Toxicity Based on United States and International Hazard Categories

Sedykh¹,

Choksi

Allen

et al. 2022

Chem. Res. Toxicol.

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Occupational Toxicology in the Pharmaceutical Industry

Dolan

Bercu

Graham³

et al. 2023

Patty's Toxicology

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Much of the activity in the pharmaceutical industry has its origins in the fine chemicals industry of the late nineteenth century. At that time, advances in chemistry and medicine led to the manufacture of pharmacologically active small molecules to produce desirable biological effects to treat diseases and illnesses at relatively low doses. Advances in biology and chemistry in the past quarter century have led to an increase in innovation resulting in a variety of novel modalities, especially recombinant proteins, antibody‐drug conjugates, cell and gene therapies, peptides and polypeptides, oligonucleotides, and vaccines. The roles and responsibilities of occupational toxicologists in the pharmaceutical industry have expanded dramatically in the twenty‐first century, commensurate with the changing regulatory requirements and treatment modalities. The occupational toxicologists' roles have become increasingly multidisciplinary and the scope of their involvement has expanded to encompass diverse aspects of worker safety as well as patient safety, and to include involvement throughout a molecule's development, from early development through postcommercialization.

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Analysis of health concerns not addressed by REACH for low tonnage chemicals and opportunities for new approach methodology

Botham,

Cronin,

Currie

et al. 2023

Arch Toxicol

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In Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) the criterion for deciding the studies that must be performed is the annual tonnage of the chemical manufactured or imported into the EU. The annual tonnage may be considered as a surrogate for levels of human exposure but this does not take into account the physico-chemical properties and use patterns that determine exposure. Chemicals are classified using data from REACH under areas of health concern covering effects on the skin and eye; sensitisation; acute, repeated and prolonged systemic exposure; effects on genetic material; carcinogenicity; and reproduction and development. We analysed the mandated study lists under REACH for each annual tonnage band in terms of the information they provide on each of the areas of health concern. Using the European Chemicals Agency (ECHA) REACH Registration data base of over 20,000 registered substances, we found that only 19% of registered substances have datasets on all areas of health concern. Information limited to acute exposure, sensitisation and genotoxicity was found for 62%. The analysis highlighted the shortfall of information mandated for substances in the lower tonnage bands. Deploying New Approach Methodologies (NAMs) at this lower tonnage band to assess health concerns which are currently not covered by REACH, such as repeat and extended exposure and carcinogenicity, would provide additional information and would be a way for registrants and regulators to gain experience in the use of NAMs. There are currently projects in Europe aiming to develop NAM-based assessment frameworks and they could find their first use in assessing low tonnage chemicals once confidence has been gained by their evaluation with data rich chemicals.

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Second Edition - Guidance Document on Integrated Approaches to Testing and Assessment (IATA) for Serious Eye Damage and Eye Irritation

Cited by 3 publications

References 66 publications

Mixtures-Inclusive In Silico Models of Ocular Toxicity Based on United States and International Hazard Categories

Mixtures-Inclusive In Silico Models of Ocular Toxicity Based on United States and International Hazard Categories

Occupational Toxicology in the Pharmaceutical Industry

Analysis of health concerns not addressed by REACH for low tonnage chemicals and opportunities for new approach methodology

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