The toxic potency of 2,3-pentanedione relative to diacetyl.
Dankovic DA; Smith RJ
Toxicologist 2014 Mar; 138(1):169
Diacetyl is often used in the food flavoring and production industries and occupational exposure to this substance has been associated with severe respiratory responses in workers. 2,3-Pentanedione (PD) has been used as a substitute for diacetyl; it is also of concern because of its structural similarities and because toxicological studies show similar pathologic responses in the upper and lower respiratory tracts of experimental animals. An earlier analysis of the relative toxic potency of PD and diacetyl was based on pilot study data (n=5 per dose group) for diacetyl, in male mice only. This analysis presents an updated comparative potency analysis of PD relative to diacetyl, based on new data for diacetyl. A 2-week + 2 day inhalation study of rats and mice exposed to PD (n=6 per dose group) was compared to a recent 13-week NTP study of diacetyl in male and female mice and rats (n=10 per dose group), as well as the male mouse pilot study data. The results are based on multinomial regression modeling of severity-ordered pathological response data. Benchmark concentrations (BMCs) for lesion scores of 1+ (at least minimal) were estimated for those models having a significant dose-response (P<0.05) and an adequate fit (P>0.05). A more complex model was necessary for estimating mouse BMCs, in which quadratic dose terms significantly improved the fit, and adjustments for the different durations of these studies were incorporated. The relative potency estimates (diacetyl/PD) range from 0.81-7.3, depending on sex and the specific endpoint evaluated (where 1.0 would indicate equal toxic potency for the two compounds). Model-based 95% confidence limits range from 0.55-14, and the range increased to 0.44-21 when adjusted for overdispersion. These results suggest that equal or greater toxic potency for PD relative to diacetyl cannot be ruled out on the basis of currently available data.
Toxicology; Cell-function; Cellular-function; Cell-damage; Exposure-levels; Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Molecular-structure; Molecular-biology; Laboratory-animals; Animals; Pathology; Biomarkers; Aerosols; Air-samples; Work-environment; Workers; Risk-factors; Food-additives; Respiratory-irritants; Respiration; Respiratory-system-disorders
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona