Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Assessment based upon available information.
Adequacy of study:
key study
Study period:
not applicable
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Information selected for the toxicokinetic assessment is primarily study data. Studies were conducted inaccordance with recognised testing guidelines. While some studies not been conducted under GLP certification due to the age of the study and geographical location, all studies were conducted in reputable contract research organisations using specifically bred models that are fully validated for the types of study. All data used for the toxicokinetic assessment is rated at least 2 for relevance and reliability (based upon Klimisch, 1997) and were conducted upon the registered substance, Methylenebis (dibutyldithiocarbamate).

Data source

Reference
Reference Type:
other: Desk study
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
All available information on Methylenebis (dibutyldithiocarbamate) has been reviewed and assessed to produce a report on the toxicokinetic properties of the subtsance.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous

Results and discussion

Any other information on results incl. tables

The following information on Methylenebis (dibutyldithiocarbamate) was used for the assessment:

 

Physical form: viscous liquid

Water solubility: 0.247 mg/l at 20 ± 5 ºC

Log Pow: 8.42 at 35 ºC

Vapour pressure: <0.13E-08 Pa

Boiling point: Does not boil prior to decomposition (≥ 250 ºC)

Molecular weight: 422.7784

Hydrogen bond donors: 0

Hydrogen bond acceptors: 0

 

Based upon the above information Methylenebis (dibutyldithiocarbamate), is not expected to be absorbed via the oral route in accordance with Lipinski's rule of five. The low water solubility and high Log Pow of the substance indicate that Methylenebis (dibutyldithiocarbamate) is not easily absorbed in the body. No information is currently available on possible degradation products produced in the gastrointestinal tract.

 

During acute and repeat dose studies no systemic or local effects were noted at doses which humans are likely to come into contact. An increase in liver weight and decrease in body weight was noted in females receiving between 314.0 - 398.6 mg/kg bw/day in the repeat dose toxicity study. Effects on males were only noted at the 1278.5 - 1957.0 mg/kg bw/day dose level. The increase in absolute and relative liver weight indicates that the liver is the main site of metabolism. No observations on excretion were noted, it is therefore not possible to determine the main route of excretion. If the liver is indeed the main site of metabolism it is likely that excretion will be through the bile (feaces).

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
Information selected for the toxicokinetic assessment is made up of test study data. Based upon the selected data Methylenebis (dibutyldithiocarbamate) is expected to have low bioaccumulation potential.