Dibutyl [[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]succinate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other:

Adequacy of study:

key study

Study period:

May 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information selected for the toxicokinetic assessment is primarily study data. Studies were conducted inaccordance with recognised testing guidelines.

Data source

Reference

Reference Type:

other: Assessment

Title:

Unnamed

Year:

2018

Results and discussion

Any other information on results incl. tables

The physical state of the substance, Butanedioic acid, 2-[[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]-, 1,4-dibutyl ester (CASRN 68413-48-9),is a pale yellow, clear liquid at room temperature and therefore, potential inhalation of the substance is negligible.

 

The water solubility is expected to be very low and partition coefficient (Log Pow) of the substance is > 6.5, respectively.  The typical molecular mass of the substance (C₂₈H₅₅O₆PS₂) is 582.84 Daltons.  These data indicate that the substance is relatively large (> 500 Daltons), has very low water solubility (< 0.1 mg/L), and is a highly lipophilic (Log Pow > 5.6) molecule, and therefore, the substance is not bioavailable via the oral route in accordance with Lipinski's rule of five.  In addition, acute oral toxicity study of the substance in rats concluded its oral LD₅₀of 11300 mg/kg body weight. Repeated dose oral toxicity studies in rats did not show any systemic effects up to 1000 mg/kg/day, the highest doses tested in both 14-day oral toxicity study and combined repeated dose oral toxicity study with the reproductive/developmental toxicity screening test.  No information is currently available on possible degradation products produced in the gastrointestinal tract.

 

The very low water solubility, high lipophilicity, and relatively large molecular mass of the substance also indicate that it is not expected to be absorbed via the dermal route.  Skin irritation test in rabbits showed that the substance is not a skin irritant. Although thelocal lymph node assay (LLNA) in mouse showed an EC₃of 50.1% that was likely due to an impurity of the test substance,dibutyl fumarate (CASRN 105-75-9), under the conditions of the test. The purity of the test item used in the LLNA was 84% and the certificate of analysis showed the test item contained approximately 0.5% (w/w) dibutyl fumarate, a known sensitizer, based on the MS area from LC-MS. The quantitative structure-active relationship (QSAR) analysis showed that the substance had no protein binding alerts. Therefore, the substance itself was not considered to be a skin sensitizer.

 

Additionally, the ready biodegradability test of the substance showed that it was not readily biodegradable. The measured test concentrations of the substance in aquatic medium were extremely low, approximately0.0024mg/L in the acute toxicity test in fish. The substance is therefore expected to have low potential for bioaccumulation in aquatic organisms although the substance is persistent and its Log Pow exceeds 5.

 

In conclusion, based upon the available data, bioavailability ofthe substance, Butanedioic acid, 2-[[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]-, 1,4-dibutyl ester (CASRN 68413-48-9),is expected to be very limited and the substance has low systemic toxicity.

Applicant's summary and conclusion

Conclusions:

In conclusion, based upon the available data, bioavailability ofthe substance, Butanedioic acid, 2-[[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]-, 1,4-dibutyl ester (CASRN 68413-48-9),is expected to be very limited and the substance has low systemic toxicity.