Reaction products of tetrabromophthalic anhydride with 2,2'-oxydiethanol and methyloxirane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other:

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: toxicokinetic statement

Justification for type of information:

REACH requires a theoretical assessment of the toxicokinetic behavoir of the substance.

Materials and methods

Objective of study:

other: toxicokinetic assessment

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

ADME assessment based on available physical chemical, structural and toxicological information.

GLP compliance:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Absorption: The components with molecular weights of > 1000 and a high molecular volume are unlikely to be taken up after oral or dermal administration. Due to the highly viscous nature of the substance inhalation exposure is highly unlikely.
The lower molecular weight products had modelled log Kow values between 3.8 and 4.1 and are likely to be absorbed in the gastrointestinal tract. Dermal toxiicty of lower molecular weight analogs is very low and dose not indicate cosniderable absortption.

Details on distribution in tissues:

After oral absorption the lower molecular weight components are likely metabolised in the liver by esterases yielding propyleneglycol and diethyeleneglycol which are further metaolised and excreted and 1,2-Benzene dicarboxylic acid, 3,4,5,6-tetrabromo. The acid may undergo glucuronidation or sulfatation to more hydrophilic components that are likely to be excreted via the urine or the gut. Oxidative metabiolism in the form of oxidative decarboxylation could also occur, but is less likely. Therefore the distribution of the parent will be relatively limited and an accumulation in fat tissue or othr tissues is not expected.

Details on excretion:

After oral absorption the lower molecular weight components are likely metabolised in the liver by esterases yielding propyleneglycol and diethyeleneglycol which are further metaolised and excreted and 1,2-Benzene dicarboxylic acid, 3,4,5,6-tetrabromo. The acid may undergo glucuronidation or sulfatation to more hydrophilic components that are likely to be excreted via the urine or the gut. Oxidative metabiolism in the form of oxidative decarboxylation could also occur, but is less likely.

Metabolite characterisation studies

Details on metabolites:

After oral absorption the lower molecular weight components are likely metabolised in the liver by esterases yielding propyleneglycol and diethyeleneglycol which are further metaolised and excreted and 1,2-Benzene dicarboxylic acid, 3,4,5,6-tetrabromo. Propyleneglycol and diethyeleneglycol are likely further metaolised and rapidly excreted. The acid may undergo glucuronidation or sulfatation to more hydrophilic components that are likely to be excreted via the urine or the gut. Oxidative metabiolism in the form of oxidative decarboxylation could also occur, but is less likely.

Applicant's summary and conclusion

Conclusions:

Only the lower molecualr weight parts of the UVCB substance are likely to be absorbed in particular when dosed via the oral route. Inhalation exposure is unlikely dur to the highly viscous character of the substance. Given the low dermal toxicity of lower molecular weight analogs dermal absorption is considered negligible. The lower molecula weight one ring components with predicted log Kow values between 3.8 and 4.1 can be absorbed and distributed. They are likely to undergo ester hydrolysis in the liver and potetially blood and other organs as esterases are occuring in many tissues. Primary metabolites after ester bond cleavage are propyleneglycol, diethyleneglycol and 1,2-Benzene dicarboxylic acid, 3,4,5,6-tetrabromo. Propyleneglycol and diethyeleneglycol are likely further metabolised and rapidly excreted. The acid may undergo glucuronidation or sulfatation to more hydrophilic components that are likely to be excreted via the urine or the gut. Oxidative metabiolism in the form of oxidative decarboxylation could also occur, but is less likely. In conclusion it is anticipated that the lowe molecular weight fractions of the UVCB can be taken up to a certain extedn in particular via the GI-tract and are likely rapidly metabolised. The metabolites are expected to be rapidly excreted.

Executive summary:

Only the lower molecualr weight parts of the UVCB substance are likely to be absorbed in particular when dosed via the oral route. Inhalation exposure is unlikely dur to the highly viscous character of the substance. Given the low dermal toxicity of lower molecular weight analogs dermal absorption is considered negligible. The lower molecula weight one ring components with predicted log Kow values between 3.8 and 4.1 can be absorbed and distributed. They are likely to undergo ester hydrolysis in the liver and potetially blood and other organs as esterases are occuring in many tissues. Primary metabolites after ester bond cleavage are propyleneglycol, diethyleneglycol and 1,2-Benzene dicarboxylic acid, 3,4,5,6-tetrabromo. Propyleneglycol and diethyeleneglycol  are likely further metabolised and rapidly excreted. The acid may undergo glucuronidation or sulfatation to more hydrophilic components that are likely to be excreted via the urine or the gut. Oxidative metabiolism in the form of oxidative decarboxylation could also occur, but is less likely. In conclusion it is anticipated that the lowe molecular weight fractions of the UVCB can be taken up to a certain extedn in particular via the GI-tract and are likely rapidly metabolised. The metabolites are expected to be rapidly excreted.