Dimethyl naphthalene-2,6-dicarboxylate

Endpoint summary

Description of key information

NDC has a low potential for bioaccumulation within the body.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Non-human information

The toxicokinetics of NDC (the registered substance) are informed by the known toxicokinetics of the analogue substance dimethyl terephthalate (DMT) (CAS 120-61-6). The behaviour of DMT in rats has been reported to be that after single or multiple oral doses of 14 C labelled DMT (at either 20mg/kg or 40mg/kg) there was significant absorption from the gastrointestinal tract. Radioactivity was excreted primarily via the urine (75-81%) with a minor component retained in the faeces.  Radioactivity did not accumulate in the tissues after repeat dosing. (Moffitt et al, 1975).  In a further study in rats, only terephthalic acid (CAS 100-21-0) was detected as a metabolite in the urine. In contrast, in similar studies in mice, the majority of DMT was excreted in urine as a monomethyl ester (70%) and 30% as Terephthalic acid. (Heck 1980). It is likely that some DMT is also metabolised to monoester and free acid by the gut microflora.  

 

In an investigation of dermal absorption a single dose of 80mg 14 C DMT in 0.2mls of vehicle (or five repeat such doses over 10 days) was dosed to depilated rat skin under occluded dressings.  Total radioactivity excretion was monitored in urine and faeces and accounted for 11% of the single dose and 13% of the multiple dose after 10 days. (Moffitt et al, 1975).

 

On the basis of the parallels with DMT the toxicokinetic behaviour of NDC would be expected to be readily absorbed via the gut (Log Kow of NDC = 3.5 versus log Kow of DMT = 2.25) and metabolised to give the mono-methyl ester and the corresponding acid (naphthalene-2,6-dicarboxylic acid, NDA, CAS 1141-38-4).  The metabolites would be expected to be excreted via the urine primarily as the free acid (NDA) using renal organic acid transport mechanisms. Similarly a small proportion of the applied dose might be expected to be absorbed via the skin and excreted via the urine as metabolites after occluded dermal exposure – particularly if formulated in an appropriately lipophilic vehicle.

 

Granulometry indicates that only 2.24% of the NDC material is less than 100 micrometres in diameter so the majority of solid material (> 97%) is not inhalable.  Any material trapped in the upper respiratory tract that is swallowed would be expected to be well absorbed and excreted as acid or monoester in the urine. 

Human information

No specific information is available but it would be expected that handling of NDC by man would be broadly similar to that seen in the rat, with ready absorption and significant and rapid excretion of urinary metabolites.

Summary and discussion of toxicokinetics

Ingested NDC will be principally the subject of rapid absorption from the gastro-intestinal tract and urinary metabolites (primarily expected to be the free acid NDA) will be excreted. Under optimised conditions of vehicle and occlusion, dermal exposure may result in clear uptake of perhaps about 10% of the applied dose. Under more normal exposure conditions however (exposure to powder with water) uptake via the skin would be expected to be negligible.