Dioctyltin dilaurate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference 1

Reference Type:

other company data

Title:

Unnamed

Year:

2015

Report date:

2015

Reference 2

Reference Type:

other: Comment to CLH Proposal

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Objective of study:

metabolism

other: Hydrolysis under stomach conditions

Test guideline

Qualifier:

no guideline required

GLP compliance:

no

Test material

Specific details on test material used for the study:

Dioctyltin dilaurate

Radiolabelling:

no

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

dimeric Distannoxane

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

There is no bioavailability of the dimeric Distannoxane based on a molecular mass of > 1000 DA

Applicant's summary and conclusion

Conclusions:

DOTL in-vitro metabolism can be monitored using 119Sn-NMR Spectroscopy. Under the simulated gastric conditions (0.1 M HCl/pH 1.2/37°C) the tin resonance at -155 ppm characteristic to DOTL (Annex 1) disappeared completely indicating that DOTL has been used up within 0.5-4.0 hour of the experiment. Main products of the hydrolysis (Annex 2 and 3) are DOTLC, (DOTCL)2O and a DOTO complex. (DOTCL)2O was detected as two sharp peaks at -92 ppm and -145 ppm
Increasing the exposure time from 30 min. to 4 hours slightly increased the amount of DOTLC and decreased the amount of the DOTO complex (Annex 2 and 3).
Formation of the dialkytin mono-chloro carboxylates is described in literature 2). This type of hydrolytic behavior at low pH is consistent with the results obtained on hydrolysis of dialkyltinmecaptides4-6). The dialkyltin mono-chloro esters are formed under the same conditions rapidly and equilibrated with the initial dialkyltin mecaptides.

A broad signal at about 150 ppm was assigned to the DOTO complex. On one hand, the DOTO reference material results in a comparable chemical shift with a broad signal (Annex 6), on the other hand, DOTO is not known to be soluble in hexane. Therefore, the DOTO complex term in this study describes a hexane-extractable solution of DOTO in DOTLC or DOTL.
Alkyltincarboxylates are known for their rich structural variety which includes different ways of coordinating the carboxyl groups and tin atoms and their ability to form bridged chemical structures2,3). Additionally, bulky alkyl groups (such as octyl groups) on a tin atom of the dialkyltin oxides are known to form more soluble cyclic trimers as opposed to dialkyltin oxide polymers7).
Addition of a DOTC excess resulted in an instant reaction of the DOTO complex to DOTLC.
In order to check if any non-extractable by hexane tin compounds were formed as a result of DOTL in-vitro metabolism and remained in the aqueous phase, that phase was analyzed for a total tin content using AAS. The total tin content of the aqueous phase was found to be < 10 ppm (trace quantity).
In a hydrolysis study of Dioctyltin dilaurate with 0.1 M Hydrogenchloride (4h, 37 ^C) was identified a distannoxane as hydrolysis product. In an similar experiment with Dioctyltin dichloride also was identified a distannoxane as hydrolysis.
Based on 119Sn-NMR data and data from mass spectroskopy, the distannoxane is minimum monomeric with a mass > 1000 Da.
So even if formed by both substances (source and target) under low pH conditions this substance cannot pass the
membranes of the gastrointestinal tract and thus is toxicological not of relevance