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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Literature review
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Review of physico-chemical and other relevant information leading to an understanding of toxicokinetics
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no test material needed

Administration / exposure

Statistics:
not applicable

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
The relatively small molecular weight (210.4) and the moderately water solubility (12.3 g/L) are favorable for absorption. In addition, the moderate log Pow value (2.03) are favorable for absorption by passive diffusion.
Type:
distribution
Results:
The small molecular weight and moderate water solubility are favorable for distribution throughout the body.
Type:
metabolism
Results:
The results of repeated dose studies indicate that the substance or its metabolites are distributed to various organs. Genotoxicity studies with and without metabolic activation do not provide further indications on the metabolic pattern of AMICURE PACM.
Type:
excretion
Results:
Low molecular weight and moderate water solubility are favorable for excretion of AMICURE PACM in urine.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The relatively small molecular weight (210.4) and the moderately water solubility (12.3 g/L) are favorable for absorption. In addition, the moderate log Pow value (2.03) are favorable for absorption by passive diffusion, although the potentially ionisable groups of AMICURE PACM, might limit diffusion across biological membranes.
For risk assessment purposes oral absorption of AMICURE PACM is set at 100%. The results of the acute oral toxicity study and the combined repeated dose reproduction study do not provide reasons to deviate from this proposed oral absorption factor; the LD50 and the NOAEL from these studies indicate that the substance becomes systemically available.
expected that AMICURE PACM will reach the nasopharyncheal region or subsequently the tracheobranchial or pulmonary region. If AMICURE PACM reaches the tracheobronchial region, absorption through aqueous pores will be limited, taking the molecular weight of > 200 into account. However, AMICURE PACM would readily dissolve into the mucus lining of the respiratory tract and the log Pow (2.03) of AMICURE PACM is favorable for absorption directly across the respiratory tract epithelium by passive diffusion. Overall, although AMICURE PACM will not reach the tracheobranchial region in a large extent, for risk assessment purposes the inhalation absorption of AMICURE PACM is set at 100%.
Details on distribution in tissues:
Once absorbed, the small molecular weight and moderate water solubility are favorable for distribution throughout the body. The results of the combined 28-day reproduction study indicate that AMICURE PACM or its metabolites are widely distributed throughout the body, based on the effects seen in various organs (e.g. liver, brain, kidneys and eyes). Possible ionization, low molecular weight and moderate water solubility are favorable for excretion of AMICURE PACM in urine.
AMICURE PACM being a liquid has the potential to partition from the stratum corneum into the epidermis. In addition, the log Pow of 2.03 is favorable for penetration into the stratum corneum and hence dermal absorption and the moderate water solubility of AMICURE PACM will not limited dermal absorption.
Details on excretion:
Possible ionization, low molecular weight and moderate water solubility are favorable for excretion of AMICURE PACM in urine.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
The results of the combined 28-day reproduction study indicate that AMICURE PACM or its metabolites are widely distributed throughout the body, based on the effects seen in various organs (e.g. liver, brain, kidneys and eyes). Available data of AMICURE PACM (e.g. negative results from in vitro genotoxicity studies with and without metabolic activation) do not give further indications on the metabolic pattern of AMICURE PACM.

Any other information on results incl. tables

Based on the present available data, no additional conclusions can be drawn on the distribution, metabolism and excretion of AMICURE PACM after dermal and inhalatory absorption.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
A review of the toxicokinetic behaviour of 4-4’-methylenedicyclohexanamine was undertaken. The relatively small molecular weight (210.4) and the moderately water solubility (12.3 g/L) are favorable for absorption, distribution and excretion. The moderate log Pow value (2.03) are favorable for absorption by passive diffusion, although the potentially ionisable groups of the substance, might limit diffusion across biological membranes. Based on the present available data, no additional conclusions can be drawn on the distribution, metabolism and excretion of AMICURE PACM after dermal and inhalatory absorption. There is a low risk of bioaccumulation of this substance.
For risk assessment purposes oral absorption of AMICURE PACM is set at 100%.