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Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Metabolism and pharmacokinetics of deuterium-labelled di-2-(ethylhexyl) adipate (DEHA) in humans
Author:
Loftus, N.J., Laird, W.J.D., Steel, G.T., Wilks, M.F. and Woollen, B.H.,
Year:
1993
Bibliographic source:
Fd Chem. Toxic. Vol . 31, No. 9. pp. 609-614

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-ethylhexyl) adipate
EC Number:
203-090-1
EC Name:
Bis(2-ethylhexyl) adipate
Cas Number:
103-23-1
Molecular formula:
C22H42O4
IUPAC Name:
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)

Method

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:
measured
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

Results:
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

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