CHLOROFORM: EXPOSURE ESTIMATION, HAZARD CHARACTERIZATION, AND EXPOSURE-RESPONSE ANALYSIS
Notice bibliographique
Résumé
Chloroform has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to chloroform principally through inhalation of indoor air, particularly during showering, and through ingestion of tap water. Data on concentrations of chloroform in various media were sufficient to serve as the basis for development of deterministic and probabilistic estimates of exposure for the general population in Canada. On the basis of data acquired principally in studies in experimental animals, chloroform causes hepatic and renal tumors in mice and renal tumors in rats. The weight of evidence indicates that chloroform is likely carcinogenic only at concentrations that induce the obligatory precursor lesions of cytotoxicity and proliferative regenerative response. Since this cytotoxicity is primarily related to rates of formation of reactive, oxidative metabolites, dose response has been characterized in the context of rates of formation of reactive metabolites in the target tissue. Results presented here are from a "hybrid" physiologically based pharmacokinetic (PBPK) animal model that was revised to permit its extension to humans. The relevant measure of exposure response, namely, the mean rate of metabolism in humans associated with a 5% increase in tumor risk (TC05), was estimated on the basis of this PBPK model and compared with tissue dose measures resulting from 24-h multimedia exposure scenarios for Canadians based on midpoint and 95th percentiles for concentrations in outdoor air, indoor air, air in the shower compartment, air in the bathroom after showering, tap water, and food. Nonneoplastic effects observed most consistently at lowest concentrations or doses following repeated exposures of rats and mice to chloroform are cytotoxicity and regenerative proliferation. As for cancer, target organs are the liver and kidney. In addition, chloroform has induced nasal lesions in rats and mice exposed by both inhalation and ingestion at lowest concentrations or doses. The mean rate of metabolism associated with a 5% increase in fatty cysts estimated on the basis of the PBPK model was compared with tissue dose measures resulting from the scenarios already described, and lowest concentrations reported to induce cellular proliferation in the nasal cavities of rats and mice were compared directly with midpoint and 95th percentile estimates of concentrations of chloroform in indoor air in Canada. The degree of confidence in the underlying database and uncertainties in estimates of exposure and in characterization of hazard and dose response are delineated.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».