Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Assessment based upon available information.
Adequacy of study:
key study
Study period:
April 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

Materials and methods

Results and discussion

Any other information on results incl. tables

The physical state of the substance, zinc bis(dipentyldithiocarbamate),is yellow translucent liquid and therefore, potential inhalation of the substance is negligible.

 

The water solubility and partition coefficient (Log Pow)of the substance are 0.086 mg/L and > 9.4, respectively.  The typical molecular mass of the substance (C22H44N2S4Zn) is 530.27 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 thus the absorption via the oral route is limited in accordance with Lipinski's rule of five.  In addition, acute oral toxicity study in rats did not show any systemic effects up to 2000 mg/kg, the highest doses tested.  Although the substance was not tolerated after 3 doses at 500 mg/kg/day or 2 doses at 1000 mg/kg/day and the rats were euthanized due to local effects on fore stomach and corresponding poor clinical conditions in the repeated dose oral range-finding toxicity study in rats, the substance did not induce any systemic effects up to 250 mg/kg/day, the highest doses tested in the combined repeated dose oral toxicity study with the reproductive/developmental toxicity screening test in rats.  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.  Thelocal lymph node assay (LLNA) in mouse and skin irritation testin vitroshowed that the substance is neither a skin sensitizer nor a skin irritant.

 

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 very low, less than its water solubility (0.086 mg/L) in the acute toxicity tests in aquatic organisms (algae, daphnia, and fish).  The substance is therefore expected to have low potential for bioaccumulation in aquatic organisms although the Log Pow of the substance exceeds 5.

 

In conclusion, based upon the available data, bioavailability ofthe substance, zinc bis(dipentyldithiocarbamate),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, zinc bis(dipentyldithiocarbamate),is expected to be very limited and the substance has low systemic toxicity.