1,4-butanediyl diacrylate

Endpoint summary

Additional information

There are no studies available assessing the absorption or metabolism of1,4-butanediyl diacrylate (BDDA).BDDA is a water clear, colorless liquid at 20 °C. It has a molecular weight of 198 g/mol, a vapor pressure of 0.00422 hPa (at 20°C), a log pow of 1.9 (at 23°C), and a water solubility of 3.1 g/l.

Oral absorption

Absorption is a property of a substance to cross biological membranes. Generally, oral absorption is favored for molecular weights below 500 g/mol and log Pow values between -1 and 4. Therefore, BDDA with a molecular weight of 198 g/mol and a log pow of 1.9 most likely diffuses very well across intestinal membranes. Furthermore, in a subacute oral toxicity study, rats were administered 20-200 mg/kg bw BDDA by gavage once daily [1]. The adjusted liver weights for males receiving Laromer BDDA at 200 mg/kg/day killed after 5 weeks of treatment were significantly increased compared to the control values. This change was considered adaptive and as a consequence of increased metabolic activity. Meaning altogether, there’s given proof for intestinal uptake of BDDA.

Dermal absorption

Liquids, like BDDA, and substances in solution are taken up more readily than dry particulates via dermal absorption. In general, dermal absorption is favored by small molecular weights and high water-solubility of the substance. Log Pow values between 1 and 4 favor dermal absorption, particularly if water solubility is high. The high water-solubility of 3.1 g/l together with the log pow of 1.9 of BDDA are conferred with a high dermal uptake. Additionally, in an acute dermal toxicity study dose levels of 400-2000 mg/kg bw BDDA were administered to rats [2]. Mortality, unsteady breathing, apathy and staggering were observed, indicating bioavailability of BDDA also via the dermal route. But it must be considered, that effects overserved were possibly induced by the irritating potential of BDDA and are therefore possibly no systemic effects.

Inhalation absorption

Absorption via the respiratory route also depends on physico-chemical properties like vapor pressure, log Pow and water solubility. BDDA has a low vapor pressure of 4.22 Pa at 20°C. Therefore, inhalation of vapor of the respective substance is very unlikely to occur. Theoretically, if inhalation of the substance occurred during handling, BDDA might be dissolved in the mucus of the respiratory tract due to its high water-solubility (3.1 g/l). Absorption directly across the respiratory tract epithelium by passive diffusion is also possible. Additionally, in a standardized inhalation hazard test with a saturated vapor atmosphere, more than half of the rats died after 1, 3 and 8 h exposure respectively [3], indicating a bioavailability of BDDA also via the inhalation route. But it must be considered, that effects overserved were possibly induced by the irritating potential of BDDA and are therefore possibly no systemic effects.

Based on the results of the described toxicity studies, an indication of oral, dermal or inhalation uptake of BDDA is given. Therefore, bioavailability can be considered to be existent.

Metabolism

Considering the chemical structure of BDDA, metabolism may consist of epoxidation of the acrylic double bond and subsequent hydrolysis and GSH conjugation, or of an oxidation at the C terminus to the acid followed by ß-oxidation involving degradation of the alkyl chain, or of an ester hydrolysis leading to the release of acrylic acid.

Accumulation

Taking into account the log Pow (1.9), the water solubility (3.1 g/l) and the considerations on the metabolism, accumulation of BDDA is considered to be unlikely.

Excretion

BDDA is very easily metabolized yielding small and water soluble metabolites. Due to their respective molecular weights below 300 and their respective water solubility, unmetabolized leftover-BDDA and its metabolites are most likely excreted via urine.

 

References

[1] BASF study on repeated dose toxicity in rats no. 85R0376/06X087, 2018

[2] BASF study on acute oral and dermal toxicity in rats no. 78/279, 1979

[3] BASF study on acute inhalative toxicity in rats no. XIII/160, 1963