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Toxicokinetic Assessment for Isooctyl Acrylate

CAS 29590-42-9 

No studies have been conducted to determine the toxicokinetics of the substance. The material is not highly volatile with a vapor pressure of 0.8 mm Hg.

 

In the 28 day oral study, effects were noted in the kidneys of the male animals at the high dose and in the forestomachs of the female animals. It can be inferred that the substance is absorbed after oral administration. The dose descriptor for human risk assessment from the 28 day study was determined to be 1000 mg/kg. Effects seen at lower doses were rat specific effects and not considered to be relevant for human risk assessment. A 90 day repeat dose study has also been conducted at doses of 40, 150 and 600 mg/kg-day. Again, kidney effects were seen and additional immunohistochemical tests were conducted to confirm the premise that the observed kidney effects were consistent with male rat kidney syndrome. Based on these additional tests, 600 mg/kg-day was determined to be the dose descriptor for risk assessment purposes.

 

Gut et al. conducted an elimination study on a similar substance, 2-ethylhexyl acrylate, CAS 103-11-7. The fate of (14C)-2-ethylhexyl acrylate was studied in adult male Wistar rats given an intravenous (i.v.) or intraperitoneal (i.p.) injection of 10 mg/kg (0.054 mmol/kg). The elimination of radioactivity from blood was bi-exponential, irrespective of the route of (14C)-2-EHA 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 the 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)-2-EHA accounted for only 0.05% (i.v.) or 0.3% (i.p.) of the initial dose of radioactivity. The radioactivity excreted in the urine within the first 24 h post-treatment accounted for 7% (i.p.) or 14% (i.v.) of the initial dose, and only 2% was excreted as thioethers1.

 

Neither the 28-day nor the 90-day study provide an indication that isooctyl acrylate is bioaccumulative when compared to the acute toxicity study. The oral LD 50 is greater that 2000 mg/kg and if isooctyl acrylate or metabolites were accumulating, effects would have been seen at lower doses in the repeat dose studies. The high acute oral LD50 and high NOAEL in the 28-day and 90-day oral gavage studies are characteristic of a test substance that has both low systemic toxicity and is readily eliminated from the test animals (not bioaccumulative). (Materials that are bioaccumulative and/or have cumulative toxicological effects usually have NOAELs much lower than the acute oral LD50.)

 

Based on the 28 day and 90-day studies as well as the study cited above, it can be assumed that isooctyl acrylate is absorbed via oral gavage and has a half life of elimination of less than 24 hours. In conclusion, isooctyl acrylate is not considered to be bioaccumulative.

 

1.        Gut I, Vodicka P, Cikrt M, Sapota A, Kavan I. Distribution and elimination of (14C)-2-ethylhexyl acrylate radioactivity in rats. Arch Toxicol 1988;62:346-50.