Didodecyl 3,3'-thiodipropionate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP study with limited but sufficient documentation

Data source

Reference

Reference 1

Reference Type:

publication

Title:

The Fate of [l4C]Thiodipropionates in Rats

Author:

Reynolds, R.C., Astill, B. D., and Fassett, D.W.

Year:

1974

Bibliographic source:

Toxicology and applied pharmacology 28, 133-141 (1974)

Reference 2

Reference Type:

secondary source

Title:

Final Report on the Safety Assessment of Dilauryl Thiodipropionate

Author:

Liebert MA

Year:

1992

Bibliographic source:

Journal of the american college of toxicology

Reference 3

Reference Type:

secondary source

Title:

Final Safety Assessment of Thiodipropionic Acid and Its Dialkyl Esters as Used in Cosmetics

Author:

Diamante C et al.

Year:

2011

Bibliographic source:

International Journal of Toxicology 29 (Supplement 3) 137S-150S

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

limited reporting details

Principles of method if other than guideline:

The fate of the test substance (didodecyl thiodipropionate (carboxy 14C-labeled, [14C]DDTDP) after oral application to rats was investigated.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Didodecyl 3,3'-thiodipropionate

EC Number:

204-614-1

EC Name:

Didodecyl 3,3'-thiodipropionate

Cas Number:

123-28-4

Molecular formula:

C30H58O4S

IUPAC Name:

didodecyl 3,3'-sulfanediyldipropanoate

Details on test material:

Carboxy 14C-labeled didodecyl thiodipropionate ([14C]DDTDP), specific activity 60 microCi/mmol, was purified (99.2 % by chromatography) by recrystallization from aqueous acetone.

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 215 - 325 g
- Housing: in glass metabolism cages, for collection of urine, faeces and exhaled carbon dioxide
- Fasting period before study: yes (animals were starved prior to dosing)
- Water (ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

other: oral in feed, and oral by gavage

Vehicle:

other: see details on exposure

Details on exposure:

In some experiments the dose was incorporated into powdered Purina Lab Chow (20 mesh), homogenized hen’s egg (1 egg/50 g) and water to a stiff
paste which was heated and formed into sticks (10 - 12 g).

In other experiments, didodecylthiodipropionate was dissolved in corn oil and applied by gavage.

Duration and frequency of treatment / exposure:

single treatment, for both gavage and feed administration (concerning feed: after 4-8 hr any unconsumed dose of the prepared feed was removed and rats were returned to the regular diet)

Doses / concentrations

Remarks:

Doses / Concentrations:
107 and 208 mg/kg bw (gavage), 166 mg/kg bw (feed)

No. of animals per sex per dose / concentration:

1

Control animals:

no

Positive control reference chemical:

not required

Details on study design:

Elimination of the radiolabelled test substance via urine, faeces and CO2 was investigated by scintillation spectrometry, scintillation assay/planchets or in a scintillation spectrometer, respectively. Internal organs were homogenized in acetone, residues collected and dried and afterwards assayed in a Thomas-Ogg apparatus and also counted in a scintillation spectrometer.
Metabolites were isolated of urine by acid and enzymatic hydrolysis.

Details on dosing and sampling:

For feed application, rats were kept in the metabolism cages for 34 days.
For gavage application, rats were kept in the metabolism cage for 4 days or 8 days.
Urines and CO2 absorbers were processed daily. Liver, kidneys, brain, heart, lungs, whole gastrointestinal tracts and fat samples were removed at sacrifice and frozen with carcasses until assayed.

Statistics:

not applicable

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

The test substance was almost entirely absorbed from the gastrointestinal tract at fed levels of up to 208 mg/kg bw, respectively.

Main ADME results 2

Type:

distribution

Results:

Low amounts of the test substance was found in fat tissues at the last sacrifice on day 34.

Main ADME results 3

Type:

metabolism

Results:

the test substance was excreted in urine as free or as acid labile conjugate

Main ADME results 4

Type:

excretion

Results:

mostly via urine (85 - 88 %), with less in faeces (1. 8- 3.5 %) and as carbon dioxide (3 - 4 %)

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The test substance was almost entirely absorbed from the gastrointestinal tract at fed levels up to 208 mg/kg bw, respectively.

Details on distribution in tissues:

Distribution in tissues was close to normal values except the value of radioactivity in the fat was elevated at 4 days after dosing and remained so at 8 and 34 days. Data is given for liver, kidney, brain, heart, lung, gastrointestinal tract, fat and carcass.

Details on excretion:

Urinary elimination accounts for about 90% of the dose. Elimination in faeces and carbon dioxide accounts for ca 2-4% and 3-4% of the dose, respectively. More than 90% of the dose is eliminated within the first 24h. This data is given as a graph. The test substance appears to be almost completely eliminated within 3 days.
Acid hydrolysis of urine samples afforded high rates of recovery approaching 100% of the urinary radioactivity after feeding.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Dithiopropionic acid was recovered in urine free or as a acid-labile conjugate.

Any other information on results incl. tables

Table 1: Cumulative elimination in the rat after gavage and feed application

Compound	Rat no.	dose [mg/kg bw]	dose [μCi]	gavage/feed	time [days]	Elimination
						urine	carbon dioxide	faeces	total
Thiodipropionic acid	1	3.1	9.3	gavage	4	90.10%	3.10%	0.50%	93.60%
	2	650	9	gavage	4	78.10%	8.20%	0.50%	86.80%
	3	572	9.3	gavage	4	84.50%	2.80%	0.90%	88.40%
	4	551	8.9	gavage	8	88.50%	7.20%	0.20%	95.90%
	5	241	8.2	feed	34	87.40%	3.30%	0.10%	90.70%
Didodecyl thiodipropionate	1	107	3.3	gavage	4	84.60%	2.90%	3.50%	90.90%
	2	208	6.6	gavage	8	88.50%	3.90%	1.80%	94.40%
	3	166	4	feed	34	86.10%	3.20%	0.10%	89.40%