Assessing chemical carcinogenicity: hazard identification, classification, and risk assessment. Insight from a Toxicology Forum state-of-the-science workshop.

The Toxicology Forum convened an international state-of-the-science workshop Assessing Chemical Carcinogenicity: Hazard Identification, Classification, and Risk Assessment in December 2020. Challenges related to assessing chemical carcinogenicity were organized under the topics of (1) problem formulation; (2) modes-of-action; (3) dose-response assessment; and (4) the use of new approach methodologies (NAMs). Key topics included the mechanisms of genotoxic and non-genotoxic carcinogenicity and how these in conjunction with consideration of exposure conditions might inform dose-response assessments and an overall risk assessment; approaches to evaluate the human relevance of modes-of-action observed in rodent studies; and the characterization of uncertainties. While the scientific limitations of the traditional rodent chronic bioassay were widely acknowledged, knowledge gaps that need to be overcome to facilitate the further development and uptake of NAMs were also identified. Since one single NAM is unlikely to replace the bioassay, activities to combine NAMs into integrated approaches for testing and assessment, or preferably into defined approaches for testing and assessment that include data interpretation procedures, were identified as urgent research needs. In addition, adverse outcome pathway networks can provide a framework for organizing the available evidence/data for assessing chemical carcinogenicity. Since a formally accepted decision tree to guide use of the best and most current science to advance carcinogenicity risk assessment is currently unavailable, a Decision Matrix for carcinogenicity assessment could be useful. The workshop organizers developed and presented a decision matrix to be considered within a carcinogenicity hazard and risk assessment that is offered in tabular form.

Treatment of painful temporomandibular joint dysfunction with the sagittal split ramus osteotomy.

PURPOSE: We describe a new indication for the sagittal split ramus osteotomy with rigid fixation to treat patients with painful dysfunction of the temporomandibular joint. PATIENTS AND METHODS: Ten patients for whom nonsurgical management failed were found to have a mandibular condyle positioned postero-superior within the glenoid fossa with reduced joint space on corrected-axis tomograms. The sagittal split ramus osteotomy was used to reposition the proximal segment and to increase joint space. Preoperative and long-term postoperative (average, 44.7 months) symptoms and tomographic findings were retrospectively compared. RESULTS: Significant pain relief occurred postoperatively in all patients. One patient had a relapse after initial improvement. No patient developed a malocclusion. The long-term radiographic condyle-fossa relationship tended to return to its preoperative position with no relapse of clinical symptoms, except in the 1 patient. CONCLUSION: The sagittal split ramus osteotomy with rigid fixation is another procedure that can be used to treat painful temporomandibular joint dysfunction by changing the position of the mandibular condyle in the glenoid fossa.