2-Decyltetradecyl 3-[3-(2-decyltetradecoxy)-3-oxopropyl]sulfanylpropanoate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Thiobis Propanoic Acid Derivatives
The category covers thiiodipropionates that are symmetrically esterified by two linear aliphatic groups ranging in size from C10 to C24
The justification for the category is based on the expectation that the close structural similarity should result in properties that are either similar or follow a pattern that correlates with changes in the molecular weights of the compounds. The category members are high-molecular weight dithiopropionate esters that differ only in the chain length of the dialkyl ester functions and are expected to follow a regular pattern for all endpoints.
Based on the structures and molecularweights of the category members, as well as available data on category members, The predictive methods and extrapolation and interpolation of data within the category are acceptable. Data provided by other sources also demonstrate that these compounds generally have mammalian toxicities that are similar (e.g., acute oral LD 50, acute irritation thresholds, and genotoxicities) or follow a pattern that parallels changes in molecular weight (e.g., repeated-dose NOAEL).

The category is adequately supported based on chemical structure and available data.

Specific details on test material used for the study:

[C14]Thiodipropionate, specific activity 1.71 mCi/mmol

Radiolabelling:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 215g - 325g
- Fasting period before study: yes
- Housing: in glass metabolism cages, for collection of urine, feces and exhaled carbon dioxide
- Individual metabolism cages: yes

Route of administration:

other: gavage/feed

Vehicle:

other: Ethanol:Water 1:1

Duration and frequency of treatment / exposure:

single treatment

Dose / conc.:

241 mg/kg bw/day

Remarks:

feed

Dose / conc.:

650 mg/kg bw/day

Remarks:

gavage

Dose / conc.:

572 mg/kg bw/day

Remarks:

gavage

Dose / conc.:

551 mg/kg bw/day

Remarks:

gavage

Dose / conc.:

3.1 mg/kg bw/day

Remarks:

gavage

No. of animals per sex per dose / concentration:

1

Control animals:

no

Positive control reference chemical:

no

Type:

excretion

Results:

as acid labile conjugate of thiodipropionic acid or free thiodipropionic acid, >90% in urine, less than 5% as carbon dioxide

Type:

absorption

Results:

Complete absorption of thiodipropionic acid

Metabolites identified:

yes

Details on metabolites:

Dithiopropionic acid is recovered as a acid-labile conjugate if given at a dose of 3.1 mg/kg bw. At 650 mg/kg bw, the major fraction is recovered in the non-conjugated form. The acid-labile conjugate is not or only to a small fraction a glucuronidate. Further identification was not performed.

Cumulative elimination in the rat after gavage and feed application

 

					Elimination
Anima no.	Dose [mg/kg bw]	dose [μCi]	gavage/feed	time [days]	urine	carbon dioxide	feces	total
1	3.1	9.3	gavage	4	90.1%	3.1%	0.5%	93.6%
2	650	9	gavage	4	78.1%	8.2%	0.5%	86.8%
3	572	9.3	gavage	4	84.5%	2.8%	0.9%	88.4%
4	551	8.9	gavage	8	88.5%	7.2%	0.2%	95.9%
5	241	8.2	feed	34	87.4%	3.3%	0.1%	90.7%

Conclusions:

No bioaccumulation potential based on study results.

Executive summary:

Thiodipropionic acid and its esters are preservatives and stabilizers used in food and food packaging. The oral fate in rats, hitherto unknown, of thiodipropionic acid (TDPA), didodecyl thiodipropionate (DDTDP), and of a polyester of thiodipropionic acid with cyclohexane-1,4-dimethanol partially terminated with stearyl alcohol, POLY-TDPS-2000 (TDPS), was elucidated in evaluating TDPS as a polymer stabilizer. Single doses of [1-14C]TDPA were rapidly eliminated, 87–95% of 241–650 mg/kg doses being recovered in 4 days in urine (78–88%), and feces (0.1–0.9%) and as 14CO2 (3–8%). Radioactivity in tissues and organs was less than 1.5 × background. A 3-mg/kg dose of [1-14C]TDPA was handled similarly. Urinary radioactivity at the higher dose was due almost entirely to unchanged TDPA, while the lower dose apparently gave an acid-labile conjugate of TDPA. Single oral doses of [1-14C]DDTDP (107 and 208 mg/kg) were rapidly eliminated, mostly in the urine (85–88%), with less in feces (1.8–3.5%) and as 14CO2 (3–4%, by day 4); 1-day dietary feeding of 166 mg/kg gave similar results. Tissue and organ levels of radioactivity at sacrifice were close to background, with the exception of fat levels, which were elevated 34 days after dosing. Urinary radioactivity was mostly unchanged TDPA or an acid-labile conjugate. Five-hour feeding in the diet of each of 3 rats of 4.7–5.6 mg/kg of 14C-labeled TDPS prepared from [1-14C]TDPA, was almost entirely eliminated by 4 days in urine (95%) and feces (0.7%) and as 14CO2 (approx. 6%). At sacrifice 4 days after dosing, tissue and organ radioactivity was slightly above background, and at 34 days essentially normal. Almost two-thirds of the urine radioactivity was due to [1-14C]TDPA or a conjugate. TDPA is in many respects similar to a typical dicarboxylic acid after oral intake in being rapidly absorbed and eliminated in the urine largely unchanged. Simple esters and polyesters of TDPA appear to be readily hydrolyzed in the organism to the parent acid, which is then eliminated similarly to TDPA given orally.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100