Pentane-2,4-dione

Endpoint summary

Additional information

Assessment of the toxicokinetik behaviour of the test substance (CAS 123 -54 -6):

The test substance (molecular weight of 100.1 g/mol) is a yellow transparent liquid (BRRC, 1985) with a log Pow of 0.05, a water solubility of 53 g/L, and a vapor pressure of 1136 Pa (calculated from Epiwin).

Absorption

Mortality and clinical signs were observed after oral and dermal administration of the test substance (see chapter "Acute toxicity" and "Repeated dose toxicity"), which indicates a systemic distribution of the test substance.

In an inhalation study conducted in male Fischer 344 rats it could be shown that 14C-labeled 2,4-pentanedione was readily absorbed by the inhalation route. Nose-only exposure to 400 ppm 14C-labeled 2,4-pentanedione resulted in a rapid increase in plasma radioactivity during the first 3 hours of exposure, with a tendency to plateau toward the end of the 6 hour exposure period (BRRC, 1995).

Metabolism

Plasma unmetabolized 14C-labeled 2,4-pentanedione was present throughout the whole of the exposure phase in the inhalation study, but was significantly less than total 14C (BRRC, 1995). Immediately postexposure, radioacivity was present in all tissues examined, but on a concentration basis (μg equivalents/g) there was no preferential accumulation of 14C in any tissue or organ. On a total organ basis, highest contents were in liver and kidneys. Postexposure, plasma unmetabolized 14C-labeled 2,4 -pentanedione declined rapidly to undetectable concentrations by 12 hours (BRRC, 1995). After intravenous administration, there was relatively rapid clearanee of 14C from plasma, with a mean residence time of 10.3 to 12.8 hr. The apparent volume of distribution ranged from 0.78 to 2.49 L/kg, suggesting that 14C-2,4 -Pentanedione was distributed beyond the lotal body water (about 0.58 L/kg), and likely sequestered in certain lipid components.

Excretion

Elimination of 14C from plasma followed a biphasic pattern with a terminal half-life of 30.72 hours. Excretion over 48 hour; of 14C was approximately equivalent between urine (37.6 %, mainly not identified metabolites) and expired¹⁴CO₂(36.3 %), which the most part of the radioactivity was eliminated in the first 12 hours. Expired volatiles, feces, tissues and carcass accounted for 2.29, 2.78, 1.66 and 17.15 % of the total administered radioactivity dose 48 hours postdosing, respectively (BRRC, 1995). Excretion of radiolabel after intravenous administration was predominantly in urine and as 14CO2 with most of the radiolabel being eliminated in the first 24 hr. Up to, and including the 148,5 mg/kg intravenous dose, total 48 hr elimination as 14CO2 was relatively constant (36.84-41.31%) but urinary 14C excretion showed a progressive and dose-related increase. At 430 mg/kg there was a route reversal in the proportion of radiolabel exereted, with urinary radiolabel being about one-half that for 14CO2. This change in the excretory profile at the highest intravenous dose could be the result of saturation of one of the metabolic pathways for 2,4 -pentanedione and is consistent with non-linear kinetic behaviour at this dose. For all doses, excretion as volatiles in expired air was low.