Sodium O,O-di-sec-butyl dithiophosphate

Endpoint summary

Description of key information

Toxicokinetic analysis of Sodium O, O-bis(1-methylpropyl)dithiophosphate (SBP1-Na)

 

Summary

No toxicokinetic study for SBP1-Na itself is available. However the toxicokinetic behaviour can be predicted based on the available physico-chemical data and studies/information from structural similar substances also containing dialkyldithiophosphate moieties. 

Based on physicochemical characteristics, particularly water solubility, octanol-water partition coefficient, and vapour pressure, no or only limited absorption by the dermal and inhalation routes is expected for the salt SBP1-Na. For the oral route, uptake will strongly depend on the pH value and is more likely for the acidic pH environment of the stomach in which the free acid will be formed. However, even for the oral route limited absorption is expected, as the predominant effects in acute or repeated dose toxicity tests are disturbances of the gastro-intestinal tract due to the corrosive properties of the substances causing local tissue damage at high doses. Based on data from similar dialkyldithiophosphate-ester structures, the following metabolites after ester cleavage and/or oxidative desulfurization (conversion of thio to oxo) can be expected if the substance is not excreted unchanged: dithiophosphate, thiophosphate and phosphate, monoesters (with two, one or no thio being present), as well as the respective alcohol. For the substance itself as well as for the potential metabolites a fast distribution and excretion (mainly via urine) is expected. Based on the physico-chemical properties neither for SBP1-Na nor for its even more polar and high water soluble cleavage products bioaccumulation is expected. Respective experimental data for the alcohol (2-butanol) also show that this metabolite is not bioaccumulative.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

0

Absorption rate - dermal (%):

0

Absorption rate - inhalation (%):

0

Additional information

 

Physico-chemical characteristics

SBP1-Na is a white to faint reddish crystalline salt at room temperature with a molecular weight of 264 g/mol. The substance is highly soluble in water (>1000 g/l). The logP_OWof SBP1 was measured and determined to be 1.64 at 22°C and pH 1 (for the free acid). A 50% solution of the salt (SBP1-Na) has a pH of 13.2 due to the necessary excess of NaOH. SBP1-Na as expected for a salt has a very low vapour pressure of approximately 9.9 x10^-7Pa. The substance is expected to be stable in water at different pH values and not being surface active [1].

 

Absorption

Based on the low logP_OWof 1.64 for the free acid at pH 1 ( an even lower value can be expected for the salt) and the very high water solubility, no or only limited absorption by the dermal route is expected for the hydrophilic salt SBP1-Na, as long as the skin barrier is not compro­mised due to the corrosive properties of the substance.

Due to the very low vapour pressure (calculated a 9.9 x10^-7Pa) and the above described physico-chemical properties also no to very limited absorption is expected for the inhalation route.

Generally, oral absorption is favoured for molecular weights below 500 g/mol. However, the uptake will strongly depend on the pH value and is more likely for the acidic pH environment of the stomach at which the un-dissociated acid is available. Even for the oral route limited absorption is expected, as the predominant effects in acute or repeated dose toxicity tests are disturbances of the gastro-intestinal tract due to the corrosive properties of the substances causing local tissue damage.

 

Distribution

Assuming that SBP1-Na is absorbed into the body following oral intake, it will be as such or potential bound to proteins well distributed extracellular with the body fluids due to its polarity and high water solubility. This also applies for potential hydrolysis products as monoalkyl esters, dithiophosphate, thiophosphate and phosphate (see metabolism). For 2-butanol studies after oral exposure in different species also show a fast distribution [2,9,10,11]. Due its high polarity and ionic-character crossing membranes will be difficult but SBP1-Na may enter cells via direct transport through aqueous pores. Based on the results observed in reproduction and developmental studies (lack of any developmental/ reproductive toxicity) with a very similar structure analogue [1] indicate that the substance is not likely to cross the placenta. Based on its low logP_OWvalue neither SBP1-Na nor the free acid (SBP1) are considered to get enriched in fatty tissues or being bioaccumulative (see also metabolism and excretion).

 

Metabolism

Based on data from similar dialkyldithiophosphate-ester structures (dithioorganophosphate insecticides), the following metabolites after enzyme-mediated ester cleavage and/or oxidative desulfurization (conversion of thio to oxo) can be expected if the substance is not excreted unchanged: dithiophosphate, thiophosphate and phosphate, monoesters (with two, one or no thio being present), as well as the respective alcohol 2-butanol. For the inorganic salts, no further degradation is expected [3,4,5,6,7,8]. The metabolism of 2-butanol is well investigated. 2-butanol undergoes fast metabolism primarily by alcohol dehydrogenases to methyl­ethylketone (MEK) which is further hydroxylated to form 3-hydroxy-2-butanone and or butandiol. The hydroxylation product of MEK, 3-hydroxy-2-butanone is expected either to undergo conjugation with sulfate or glucuronic acid and elimination of the conjugated metabolites in the urine, or to enter intermediary metabolism to form carbon dioxide [2,9,10, 11].

 

Excretion

For the substance itself as well as for the potential inorganic metabolites a fast distribution and excretion (mainly via urine) is expected. Based on the physico-chemical properties of SBP1-Na and its even more polar and high water soluble cleavage products bioaccumulation is highly unlikely. Respective experimental data for the alcohol also show that this metabolite is quickly excreted [2,9,10,11]) or enter the intermediary metabolism to form carbon dioxide and is therefor not expected to be bioaccumulative.

 

 

References

[1] IULICD CAS 33619-92-0

[2] IUCLID CAS 78-92-2

[3] Forth W., Henschler D., Rummel W.(Hrsg): Allgeimeine und spezielle Pharmakoligie und Toxikologie.Bibliographisches Institut, 1983.

[4] Metabolism of Chlorpyrofos, US EPA, 2008

http://npic.orst.edu/factsheets/archive/chlorptech.html

[5]Laveglia J,Dahm PA. Degradation of organophosphorus and carbamate insecticides in the soil and by soil microorganisms.Annu Rev Entomol.1977;22:483-513.

[6] Malathion Pathway Map,http://eawag-bbd.ethz.ch/mal/mal_map.html

[7] Franca M. Buratti,Alessandra D'Aniello,Maria Teresa Volpe,Annarita MeneguzandEmanuela Testai:Malathion bioactiviation in the human liver: the contribution of different cytochrome P450 isoforms.Drug Metabolism and Disposition March 2005, 33 (3) 295-30

[8]El-Oshar, M. A. and Dauterman, W. C. (1979), In-vitro metabolism ofO,O-diethylS-(N-methylcarbamoylmethyl) phosphorodithioate by mouse liver. Pestic. Sci., 10: 14–18.

[9] Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 352

[10] Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 2645

[11] Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 56