Sodium 1,4-dicyclohexyl sulphonatosuccinate

Basic toxicokinetics

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:

guideline study with acceptable restrictions

Remarks:

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

Test material information

Constituent 1

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 results

Main ADME results 1

Type:

absorption

Results:

at least 65%

Main ADME results 2

Type:

metabolism

Results:

extensive (e.g. 2-ethylhexanol)

Main ADME results 3

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. The 24-48 hour urine samples from any of the animals did not yield measurable quantities of 2-ethylhexanol. 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 (migrated information): 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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