2-Propenoic acid, 2-propylheptyl ester

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No reliable studies concerning toxicokinetics, metabolism and distribution were identified for 2-propylheptyl acrylate. However, data from the structural analogues 2-ethylhexyl acrylate, and ethyl acrylate were considered for the assessment and read across approach was performed.

 

Toxicokinetics, metabolism, and distribution

There are no guideline studies on toxicokinetics, metabolism and distribution of 2 -ethylhexyl acrylate. Nonetheless, an assessment of the toxicokinetic behaviour of the substance can be made based on a variety of publications, primarily by Sapota (1988, 1990). 14C-2-EHA (labelled on the vinyl carbons) was administered p.o. and i.p. to rats at a dose of 100 mg/kg bw, respectively (Sapota 1988). The highest specific radioactivity was found three hours after i.p. administration in liver and kidneys, followed by spleen, lung, brain, adipose tissue and blood. The 14C levels decreased continuously in all tissues except in the adipose where radioactivity remained nearly constant (0.7%) for 72 hours. After oral dosing about 50% of the radioactivity was eliminated via the expired air and about 38% via the urine within the first 24 hours. A small portion of 2-EHA (about 1% of the dose) was excreted via the faeces. No specific studies have been carried out on the metabolism of 2-EHA. However a variety of studies on rats have indicated that short-chain acrylates such as ethylacrylate undergo the following metabolic reactions: carboxylesterase catalyzed hydrolysis of the ester function to release acrylic acid and alcohol (De Bethizy et al. 1987; Frederick et al. 1992). The half-life of ethylacrylate-hydrolysis in rat liver (in vitro) was approximately 2 seconds. In 13 other tissues it was as much as 15 minutes (Frederick et al. 1992). The acrylic acid is decarboxylated and degraded to carbon dioxide (Gut et al. 1988; Sapota 1988). Only a small part of approx. 2% (varies with the route of administration) of the administered 2-EHA was conjugated to glutathione and excreted as thioether (Gut et al. 1988; Vodicka et al. 1990).

Discussion on bioaccumulation potential result:

No reliable studies concerning toxicokinetics, metabolism and distribution were identified for 2-propylheptyl acrylate. However, data from the structural analogue 2-ethylhexyl acrylate (EHA) were considered for the assessment.

The distribution and excretion of 2-ethylhexyl [2,3-14C]-acrylate following intraperitoneal (i.p.) and oral (p.o.) administration to male Wistar rats at a dose of 100 mg/kg body weight was investigated by Sapota (1988). The radioactivity was absorbed rapidly and completely, independent of the route of administration.14C found in the tissues was mainly associated with liver, kidneys and lung. Loss of 14C from these tissues occurred fairly rapidly, with the exception of the rats given EHA intraperitoneally.

EHA underwent rapid metabolism and excretion with expired air (78% after i.p. and 51% of the dose after p.o. administration) and urine (10% after i.p. and 41% of the dose after p.o. administration). Only a small portion was excreted via faeces (3% after i.p. and 1% of the dose after p.o. administration). In all cases more than 90% of radioactivity had been excreted up to 72 hours after administration. Most of the radioactivity found in the expired air was quickly exhaled within the first 3 hours after administration of the acrylate. 14C in the expired air was probably present as 14CO2. At 72 hours after a single intraperitoneal administration of EHA, the total radioactivity present in the examined tissues amounted to approx. 1% of the dose, but in the fat and sciatic nerve the specific radioactivity was still relatively high. In a second study, [14C]-2-ethylhexyl acrylate was given to adult male Wistar rats intravenously (i.v.) and intraperitoneally (i.p.) at a dose of 10 mg/kg bw (Gut et al. 1988). The elimination of radioactivity from blood was bi-exponential, irrespective of the route of administration or the age (weight) of the rats. The first phase half-lives after i.v. and i.p. administration in 4-month-old rats were 30 and 60 min, in 7-month-old rats 115 and 130 min, respectively. The corresponding values for the slow-phase were 5 and 6 h, and 14 and 14 h. Elimination of radioactivity from tissues followed a pattern similar to that seen for blood. More than half of the administered radioactivity was exhaled as carbon dioxide. Exhalation of unchanged [14C]-EHA accounted for only 0.05% (i.v.) and 0.3% (i.p.) of the initial dose, respectively. The radioactivity excreted in the urine within the first 24 h post-treatment accounted for 7% (i.p.) and 14% (i.v.) of the initial dose, respectively. Only 2% was excreted as thioethers.

Exposure of male Wistar rats to 2-ethylhexyl acrylate vapours at different concentrations for 6 hours increased the absolute amounts of urinary thioether excretion in a dose-dependent manner (Vodicka et al. 1990). Most pronounced non-protein-SH depletion was observed in the liver, less in blood and moderate in brain and lungs. The authors suggested that GSH depletion may participate in acute lethal and biochemical toxic effects of acrylic acid esters. However, the portion of the acrylate ester metabolised to thioethers was low (3-8% of the inhaled dose). With increasing concentrations of inhaled EHA, the metabolised proportion of EHA decreased slightly (8.0% at 250 mg/m3, 5.5% at 500 mg/m3 and 3.0% at 1000 mg/m3).