Establishing short-term occupational exposure limits (STELs) for sensory irritants using predictive and in silico respiratory rate depression (RD50) models.
Inhal Toxicol
; 36(1): 13-25, 2024 Jan.
Article
en En
| MEDLINE
| ID: mdl-38252504
ABSTRACT
Sensory irritation is a health endpoint that serves as the critical effect basis for many occupational exposure limits (OELs). Schaper 1993 described a significant relationship with high correlation between the measured exposure concentration producing a 50% respiratory rate decrease (RD50) in a standard rodent assay and the American Conference of Governmental Industrial Hygienists (ACGIH®) Threshold Limit Values (TLVs®) as time-weighted averages (TWAs) for airborne chemical irritants. The results demonstrated the potential use of the RD50 values for deriving full-shift TWA OELs protective of irritant responses. However, there remains a need to develop a similar predictive model for deriving workplace short-term exposure limits (STELs) for sensory irritants. The aim of our study was to establish a model capable of correlating the relationship between RD50 values and published STELs to prospectively derive short-term exposure OELs for sensory irritants. A National Toxicology Program (NTP) database that included chemicals with both an RD50 and established STELs was used to fit several linear regression models. A strong correlation between RD50s and STELs was identified, with a predictive equation of ln (STEL) (ppm) = 0.86 * ln (RD50) (ppm) - 2.42 and an R2 value of 0.75. This model supports the use of RD50s to derive STELs for chemicals without existing exposure recommendations. Further, for data-poor sensory irritants, predicted RD50 values from in silico quantitative structure activity relationship (QSAR) models can be used to derive STELs. Hence, in silico methods and statistical modeling can present a path forward for establishing reliable OELs and improving worker safety and health.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Exposición Profesional
/
Irritantes
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Inhal Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido