Registration Dossier

Administrative data

dermal absorption
Type of information:
other: statement
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: An extended assessment of the toxicokinetic behaviour of Cu(2Na)IDHA was performed, taking into account the chemical structure, the available physico-chemical-data and the available toxicity data.

Data source

Reference Type:
other: Statement
Report Date:

Materials and methods

Test guideline
according to
other: TGD, Part I, Annex IV, 2003); ECHA guidance R7c., 2008
Principles of method if other than guideline:
An assessment of dermal absorption potential of Cu(2Na)IDHA is based on its physico-chemical properties and on the results of available toxicity data data.
GLP compliance:

Test material

Test material form:
other: microgranulated

Results and discussion

Percutaneous absorption
ca. 6 %
Remarks on result:
other: based on data for copper in an ex vivo study with human skin

Applicant's summary and conclusion

No significant dermal absorption is expected for the target substance.
Executive summary:

Based on physical – chemical properties of Cu (II) IDHA, the substance is not likely to penetrate skin to a large extent due to its negative logPow: -3.09 and a very high water solubility: 421 g/L. Water solubility above 10.000 mg/L combined with a logPow value below 0 indicate that the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake for these substances will be low. The molecular weight of 354.69 g/mol indicates that a certain potential to penetrate the skin (< 500) exists. However, in case of such a hydrophilic substance dermal penetration is rather unlikely. This is supported by the findings of acute dermal toxicity studies of the target substance Cu (II) IDHA as well as free IDHA and Cu (2Na) EDTA where no systemic toxicity after exposure via the skin was noted (LD50 > 2000 mg/kg bw; Kropidło, 2010, Report No. DER -13/10; Stropp, 1997, Report No. T3061600; Beerens, 2010, Report No. 494023). Moreover, an acute dermal irritation / corrosion study in the rabbit (according to OECD 404) for Cu (II) IDHA did not demonstrate any irritation after 14 days (Kropidło, 2010, Report No. DDR-15/10). This information indicates that Cu (II) IDHA is unlikely to penetrate the skin. In a human study, EDTA-CaNa2 did not penetrate the skin, only 0.001 % was absorbed within 24 hours of administration (RAR, 2004). In case of dissociated complexes, copper ions uptake across intact skin would be expected to be extremely limited (ATSDR, 2004). The available in vivo data do not provide information on the rate and extent of absorption through intact skin following dermal exposure of humans or animals to copper (ATSDR, 2004; SCOEL, 2013). In vitro studies suggest that copper is poorly absorbed through intact skin. Less than 6% of copper deposited on ex vivo human skin samples were absorbed (ATSDR, 2004). Low absorption potential through the skin would also apply to free IDHA chelating agent due to its high hydrophilicity (water solubility of 564 g/L; data for Baypure CX 100 (Bayer)).

Based on very low logPow values, high water solubility and absence of toxicity effects in animal studies conducted with different aminopolycarboxylate chelates: free chelating agent IDHA, Cu (II) IDHA, Cu (2Na) EDTA and Ca (2Na) EDTA, a similar behaviour regarding absorption through the skin is expected. Dermal absorption is considered to be negligible and equal to 6 % established for copper in an ex vivo study with human skin. This is the highest value known which will be used for hazard assessment: DNEL derivation.