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Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted to the highest possible scientific standards in a well renomated laboratory, however only limited materials and methods were provided according to the standards at the time of conduct.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report date:
1973

Materials and methods

Objective of study:
absorption
excretion
metabolism
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Docusate sodium
EC Number:
209-406-4
EC Name:
Docusate sodium
Cas Number:
577-11-7
Molecular formula:
C20H38O7S.Na
IUPAC Name:
sodium 1,4-bis[(2-ethylhexyl)oxy]-1,4-dioxobutane-2-sulfonate
Constituent 2
Reference substance name:
Butanedioic acid, sulfo-, 1,4-bis (2-ethylhexyl) ester, sodium salt
IUPAC Name:
Butanedioic acid, sulfo-, 1,4-bis (2-ethylhexyl) ester, sodium salt
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): dioctyl sodium succinate (DSS)
- Substance type: sulfosuccinate compound
- Physical state: liquid
Radiolabelling:
no
Remarks:
5 rats unlabeled; one male rat carbon-14 labeled

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: oral gavage and intravenously
Vehicle:
water
Doses / concentrations
Remarks:
Doses / Concentrations:
1. Five rats were dosed with unlabeled docusate sodium. Rat No. 1 received 1 mL and rat No. 3 received 2 mL of a 5 mg/mL solution in water by oral gavage. Rats Nos. 4 and 5 received 1 mL of a 1% solution in water by intravenous administration. In addition, one animal (rat No. 2) was given 1.05 mL of a solution of 5.5 mg/mL 2-ethyl-hexanol in 40% ethanol by oral gavage.
2. One male rat (250 g) was given 10 mg/kg 14C labeled docusate sodium by gavage (2.5 mL of a 1 mg/mL solution).
Control animals:
no
Details on dosing and sampling:
1. Total urine and feces were collected from all of the animals at 24 and 48 hours after dosage. Urine and feces from rat No. 1 were also collected at 72 hours and 96 hours.
2. Urine and feces were collected from the rat given 14C labeled DSS at 0-24h and 24-48 hours.

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
at least 65%
Type:
metabolism
Results:
extensive (e.g. 2-ethylhexanol)
Type:
excretion
Results:
in the urine (within 24h) and feces

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Table 1 shows the results of the analysis of the urine from these animals using the 2-ethylhexanol distillation procedure. Since the percent of dose excreted in the urine after intravenous dosage was comparable to the excretion after oral dosage, it is concluded that the orally administered compound is well absorbed by the rat. Since 2-ethylhexanol derivatives recovered in the urine after administration of the alcohol are appreciably lower than those recovered after DSS administration, it is concluded that the mechanism of absorption of DSS does not include prior hydrolysis of the ester groups in the gastrointestinal tract. This is further substantiated by the finding that the 2-ethylhexanol forming compound in urine after administration with DSS is largely not the free alcohol or its glucuronide conjugate.
Details on excretion:
The male animal given radioactive compound showed that the urine excreted during the first 24 hours accounted for 64.1% of the radioactivity; the feces for 37.4%. The animal was further found to eliminate 1.0% of the dose in the 24-48h urine and 0.9% of the dose in the 24-48h feces.

Metabolite characterisation studies

Metabolites identified:
yes

Any other information on results incl. tables

Table 1. 24 hour excretion of 2-ethylhexanol-forming compounds by the rat after oral dosage with DSS and 2-ethylhexanol

Rat No.

Compound

Dose (mg)

Route

% of dose excreted

Urine

Faeces

1

DSS

5

oral

18.6

0.9

3

DSS

10

oral

15.5

8.7

4

DSS

10

I.V.

12.3

-

5

DSS

10

I.V.

15.5

-

2

2-ethyl-hexanol

5.8

oral

3.1

3.9

-: not determined

Applicant's summary and conclusion

Conclusions:
Interpretation of results: no bioaccumulation potential based on study results
The compound was well absorbed, metabolised and excreted after oral administration (two thirds were oberved in the 24 hours urine; one third was found in the feces).
Executive summary:

The absorption, excretion and metabolism of dioctyl sodium succinate (DSS) have been investigated. Unlabeled DSS and radiolabeled compound (carbon-14) were used. Using a gas chromatographic procedure, a similarity in percent excretion of dose into urine was observed in rats dosed orally and intravenously, indicating a high degree of absorption of the oral dose. Confirmation of extensive absorption of DSS was obtained through oral dosage of 10 mg/kg carbon-14 labeled compound. Two thirds of the administered radioactivity was found in the urine at 24 hours after dosage. All of the activity was in the form of metabolites (2-ethylhexanol forming compounds).

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