Evaluation of inhalation TTC values with the database RepDose

Thresholds of Toxicological Concern for cosmetics-related substances: New database, thresholds, and enrichment of chemical space

“…Therefore, in addition to the fact that the POD distributions of Class II and III are not significantly different, the possibility still exists that the chemical space of Class II for cosmetics-related chemicals may be different than that of other chemicals. The difficulty of finding sufficient chemicals to populate Cramer Class II and provide a meaningful analysis has been noted by others using different databases (Batke et al, 2011;EFSA, 2012;Escher et al, 2010;Feigenbaum et al, 2015;Munro et al, 1996;Pinalli et al, 2011;Tluczkiewicz et al, 2011). The present study also found that there were insufficient chemicals in Cramer Class II for a meaningful analysis and derivation of a reliable TTC value for this Cramer Class with the database at hand.…”

“…There has also been discussion of whether it would be preferable, from a scientific perspective, to use molar quantities of chemical entities and convert NOAELs from mg/kg-bw into mmol/ kg-bw (Escher et al, 2010;Dewhurst and Renwick, 2013). This was not pursued in the present work for the COSMOS TTC dataset since the scientific community utilising the TTC approach is mostly working on a mg/kg-bw basis, and using that basis allows easier comparisons with other published TTC values.…”

“…It has also been used as a first-level screening tool to prioritize for review a large number of substances identified as needing an assessment under the Canadian Environmental Protection Act (Health Canada, 2016). Consideration has also been given to whether the TTC approach could be applied to human biomonitoring data (Becker et al, 2012) and to human exposures by non-oral routes (Carthew et al, 2009;Escher et al, 2010;Hennes, 2012;Kroes et al, 2007;Partosch et al, 2015).…”

Thresholds of Toxicological Concern – Setting a threshold for testing below which there is little concern

“…Moving away from the cancer bioassays, analyzing a reference database of more than 600 substances tested in more than 2,900 sub-chronic and chronic toxicity studies, Munro et al (1990Munro et al ( , 1996Munro et al ( , 1999 Cheeseman et al, 1999;Felter et al, 2009;Müller et al, 2006 General toxicity 0.025 -1 (depending on Cramer classes) Munro et al, 1996Munro et al, , 1999 Munro et al, 1996Munro et al, , 1999Escher et al, 2010;Bernauer et al, 2008Genotoxicity 0.025 -2 Rulis 1986, 1989Kroes et al, 2005;Müller et al, 2006 Carcinogenicity (genotoxic) 0.0025 Kroes et al, 2005;Cheeseman et al, 1999 Carcinogenicity (non-genotoxic) 0.025 -0.75 Kroes et al, 2005; (depending on Ames test and acute toxicity) Cheeseman et al, 1999 Acute toxicity (inhalation) 4 -1,000 μg/m 3 Grant et al, 2007;Escher et al, 2010 Neurotoxicity 0.3 Munro andKroes, 1998;Kroes et al, 2000 Developmental toxicity 1 a -8 -131 Munro and Kroes, 1998; (depending on Cramer class) Bernauer et al, 2008;0.5 -1 μg/m 3 (inhalation) van Ravenzwaay et al, 2011;Laufersweiler et al 2012 Reproductive toxicity 1 -100 Bernauer et al, 2008;van Ravenzwaay et al, 2011van Ravenzwaay et al, , 2012van Ravenzwaay et al, , 2017 Estrogenic endocrine disruption 0.025 Kroes et al, 2000 Immunotoxicity 0.15 -1,000 Kroes et al, 2000;Hartung and Corsini, 2013 Skin sensitization (dermal) 0.91 -900 μg/cm 2 Sa...…”

O impacto dos aditivos do tabaco na toxicidade da fumaça do cigarro: uma avaliação crítica dos estudos patrocinados pela indústria do fumo

“…This tiered testing scheme was inspired on the Threshold of Toxicological Concern (TTC) concept, a pragmatic approach developed for assessing the risk of compounds of known chemical structure for which no compound-specific toxicity data are available 48,49,50,51,52 . The TTC concept assumes that human exposure to chemicals below the corresponding TTC are very unlikely to cause any adverse effect.…”