Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
calculation (if not (Q)SAR)
Remarks:
Migrated phrase: estimated by calculation
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A written assessment of toxicokinetic behaviour is considered appropriate for the substance. A written assessment has therefore been prepared to address this endpoint.

Data source

Materials and methods

Objective of study:
other: Assessment of toxicokinetic behaviour
Principles of method if other than guideline:
Written assessment based on toxicological profile.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Not applicable

Test animals

Species:
other: Not applicable

Administration / exposure

Details on exposure:
Not applicable
Duration and frequency of treatment / exposure:
Not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
Not applicable
No. of animals per sex per dose:
Not applicable
Positive control:
Not applicable
Details on study design:
Not applicable
Details on dosing and sampling:
Not applicable
Statistics:
Not applicable

Results and discussion

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
Not applicable

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
In the acute oral toxicity study and the repeated dose toxicity studies with the test substance, signs of toxicity were observed indicating that the substance is absorbed by this route. As a worst case, absorption via the oral route is assumed to be 100%. The molecular weight (754 to 757) of the test substance is > 500 therefore the molecules may be too large to allow movement across the dermal membranes. Consequently, absorption via the dermal route is assumed to be 10%. Signs of systemic toxicity were observed in the oral toxicity studies with the substance therefore it is likely that the substance will also be absorbed if it is inhaled, however, the likelihood that inhalable atmospheres may be generated is low. As a worst case, absorption via the inhalation route is assumed to be 100%.

The substance is considered to be lipophilic (based on log Kow >0) therefore it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues. Zinc 3,5-bis(α-methylbenzyl)salicylate contains zinc and zinc is distributed to all tissues and tissue fluids in humans.

The organic component of the test substance is likely to undergo metabolism in the liver and other organs with the resultant metabolites eliminated by the kidneys in the urine. Bioaccumulation of the test substance is not expected based on its low log Kow value, water solubility and predicted metabolism.
Executive summary:

Toxicokinetic parameters such as uptake, distribution, metabolism and excretion form the essential toxicological profile of a substance. An approximate indication of the toxicokinetic pattern can be gained from the results of basic toxicity testing. The assessment of the toxicokinetic properties of zinc 3,5-bis(α-methylbenzyl)salicylate detailed below is based on the results obtained for the physical/chemistry and toxicological endpoints.

In the acute oral toxicity study and the repeated dose toxicity studies with the test substance, signs of toxicity were observed indicating that the substance is absorbed by this route. As a worst case, absorption via the oral route is assumed to be 100%.The molecular weight (754 to 757) of the test substance is > 500. Consequently, absorption via the dermal route is assumed to be 10%. As a worst case, absorption via the dermal route is assumed to be 100%. Signs of systemic toxicity were observed in the oral toxicity studies with the substance therefore it is likely that the substance will also be absorbed if it is inhaled, however, the likelihood that inhalable atmospheres may be generated is low. As a worst case, absorption via the inhalation route is assumed to be 100%.

 

The substance is considered to be lipophilic (based on log Kow >0) therefore it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues. Zinc 3,5-bis(α-methylbenzyl)salicylate contains zinc and zinc is distributed to all tissues and tissue fluids in humans.

 

The organic component of the test substance is likely to undergo metabolism in the liver and other organs with the resultant metabolites eliminated by the kidneys in the urine. Bioaccumulation of the test substance is not expected based on its low log Kow value, water solubility and predicted metabolism.