reaction products of acetic anhydride and adipic acid

Endpoint summary

Description of key information

The constituents of the target substance hydrolyses rapidly when in contact with water or moisture finally to acetic acid and adipic acid.
Absorption: Expected to occur via oral route and via lungs. 
Distribution: The hydrolysed substances are expected to distribute throughout the major tissues.
Metabolism: Acetic acid and adipic acid are oxidised to the normally occurring metabolites of lipid and protein metabolic pathways.
Excretion: The substances are partially excreted in the urine or via the lungs.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No specific studies have been conducted for the target substance. The substance is composed of acetic anhydride (5-10 wt. %), adipic acid,di-anhydride with bis(acetic acid) (50-62 wt. %) and acetic acid (30-35 wt. %). The main and the most hazardous component of this substance is acetic anhydride which has well-known corrosive and irritating effects on the eyes, skin and respiratory tract.

Since acetic anhydride is unstable in water and decomposes immediately (half-life about 4 minutes) in contact with water to acetic acid/acetate, systemic toxicity is unlikely. Thus, the toxicokinetic behaviour of acetic acid/acetate instead of acetic anhydride is focused in CSA. Adipic anhydrides hydrolyse also rapidly when in contact with water to adipic acid and acetic acid. Thus, the toxicokinetic behaviour of adipic acid is discussed below.

 

Absorption

Acetic anhydride is highly irritating and readily hydrolyses to acetic acid. Therefore, local toxicity at site of contact is observed, but not systemic toxicity.

Acetic acid is absorbed from the gastrointestinal tract and through the lungs. The acetate ion (the anion of acetic acid) is a normally-occurring metabolite in catabolism or in anabolic synthesis, e.g. in the formation of glycogen, cholesterol synthesis, degradation of fatty acids, and acetylation of amines.

Acetic acid is absorbed from the stomach of rats; the percentage absorbed decreases with increasing dose Hertling D.C., et al.(1956). The data shows that acetic acid is totally absorbed (100%) when 20 mg is gavaged, 80% when 50 mg is gavaged, 75% when 80 mg is gavaged and 30 % when 420 mg is gavaged.

In animals and humans it was shown that adipic acid is absorbed after oral administration (Rusoff, II et al., 1960).

Distribution

It is estimated that the level of the acetate ion in humans is about 50–60 µmol/l (3.0–3.6 mg/l) in plasma and 116 µmol/l (7 mg/l) in cerebrospinal fluid. Daily turnover of the acetate ion in humans is estimated to be about 7.5 µmol/kg/min representing some 45 g/day (HSDB, 2016).

At plasma pH (7.4) only about 0.23% of the acetate was unionised and able to permeate across a lipid barrier. Over a 60 min period during which plasma concentrations of acetate were maintained at 22 umol/mL, the maximum concentration in cerebral spinal fluid (CSF) was approximately 20x lower than in plasma (HSDB, 2016).

Metabolism / Excretion

Acetic acid is readily metabolized by most tissues and may give rise to the production of ketone bodies as intermediates. Metabolism of 14(C) acetate in mice results in radioactivity associated with the protein fractions of plasma and most major tissues (Bingham, E. et al., 2001). In rats given radiolabelled acetate in diet, 50 % of the radiolabel was excreted as CO2 (Lundberg, 1988).

Acetate is rapidly eliminated. Elimination half lives were 3.0±0.5, 4.0±0.3, 4.1±0.4 and 5.0±0.5 minutes at doses of 3, 4, 5 and 6 mM/kg, respectively (Freundt, KJ. 1973)

Adipic acid or adipate are partially oxidized in the lipid metabolism pathways and excreted via the kidney or the lungs (OECD; SIDS, 2004).

As acetic acid and adipic acid are metabolized and excreted rapidly, these substances are not expected to have bioaccumulation potential.