Registration Dossier

Diss Factsheets

Toxicological information

Exposure related observations in humans: other data

Administrative data

exposure-related observations in humans: other data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed according to acceptable scientific method.

Data source

Reference Type:
Metabolism and pharmacokinetics of deuterium-labelled di-2-(ethylhexyl) adipate (DEHA) in humans
Loftus, N.J., Laird, W.J.D., Steel, G.T., Wilks, M.F. and Woollen, B.H.,
Bibliographic source:
Fd Chem. Toxic. Vol . 31, No. 9. pp. 609-614

Materials and methods

Endpoint addressed:
basic toxicokinetics
Test guideline
no guideline required
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Bis(2-ethylhexyl) adipate
EC Number:
EC Name:
Bis(2-ethylhexyl) adipate
Cas Number:
bis(2-ethylhexyl) adipate
Details on test material:
DEHA was obtained from ICI Chemical and polymers (UK)
purity [2H10]DEHA > 99% and was prepared at Zeneca Central Toxicology Laboratory (Cheshire, UK)


Ethical approval:
confirmed, but no further information available
Details on study design:
Six male volunteers were received 46 mg [2H10]DEHA (purity >99%) formulated in
corn , oil (in a total volume of 0 .5 cm3) and dosed as a gelatin capsule.
Exposure assessment:
Details on exposure:
Blood samples (10 cm3) were taken from this cannula pre-dose and 0 .5, 1, 2, 3, 4, 5, 6, 8 and 12 hr post-administration.
Further samples were taken by venepuncture at 24 and 31 hr.

Urine collections were made at 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72 and 72-96 hr post-administration.

Results and discussion

No adverse effects were observed in any of the volunteers, and there were no significant changes in
biochemical or haematological parameters measured before or after administration of [2H10]DEHA .
After oral administration, unconjugated [2H10]EHA was the only compound measurable
in plasma; [2H10] EH was detected but the levels were below the limit of quantification.
[2H10 EHA] was also the principal metabolite eliminated in urine, followed by [2H5]5-OH-EHA,
[2H5]diEHA, [2H5]EH and [2H5]keto-EHA. The rates of elimination were similar for all metabolites (mean elimination half life of 1.5 hr).

Applicant's summary and conclusion