Registration Dossier

Administrative data

Endpoint:
dermal absorption
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
In vitro permeation of nickel salts through human stratum corneum.
Author:
Tanojo, H., Hostynek, J.J., Mountford, H.S. and Maibach, H.I.
Year:
2001
Bibliographic source:
Acta Derm Venereol. Suppl 212:19-23.

Materials and methods

Principles of method if other than guideline:
Measures of the permeation of these salts through the stratum corneum (SC). No standard guideline followed. Test methods are described in the following sections.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Substance type: Pure solution
- Composition of test material, percentage of components: 1% w/v nickel

Radiolabelling:
no

Test animals

Species:
other: human stratum corneum

Administration / exposure

Details on study design:
Heat-separated human stratum corneum sheets from cadavers were placed in a continuous flow-through diffusion cell system
maintained at 37 deg. C. Aqueous donor solutions of nickel salts (nitrate, sulfate, and chloride) were prepared containing 1% w/v Ni
(10 mg/ml Ni2+). HPLC-grade water was used as the receptor fluid, which was pumped at a rate of 4-5 ml/hr through the receptor side of the
diffusion cells. The receptor water was collected every 4 hours up to 96 hours. Donor solutions were collected from each diffusion cell. The
stratum corneum sheets were boiled in 10 ml of a 30% hydrogen peroxide solution for 4 hours and cooled. Analyses were conducted by ICP-MS.
The percentage of Ni compound recovered from the applied dose was determined.
The 96-h in vitro permeation profile of each nickel salt was plotted against time using Microcal Origin,
and the permeability constant of each salt was calculated from the permeation rate during steady state.
Data were analyzed using the paired Student t-test on Microcal Origin

Results and discussion

Absorption in different matrices:
The permeation of various nickel salts across human skin was relatively minute. One percent or less of the nickel salts penetrated the stratum corneum at 96 hours, and less than 1% of the salts was retained. Retention in the stratum corneum was highest for the nitrate (0.95%) and lowest for the acetate (0.10%). Percent retentions in the stratum corneum of the chloride and sulfate salts were 0.18 and 0.56%,respectively. 
 
The highest rate of permeation for all salts tested occurred within the first 24 hours. The chloride and acetate salts reached peak penetration  
within 4 hours. Nickel nitrate peaked at ca. 8 hours, while nickel sulfate peaked after 12 hours post-application. Steady state was  
obtained after 24 hours for all the nickel salts tested. 
 
The permeability constants (standard deviation) of nickel salts across human stratum corneum in vitro were reported as: 

nickel sulfate: 8.5 (5.5) cm/h x 10e-7 
nickel chloride: 6.8 (1.2) cm/h x 10e-7 
nickel nitrate: 5.2 (1.6) cm/h x 10e-7 
nickel acetate: 5.2 (1.1) cm/h x 10e-7 

Any other information on results incl. tables

The permeation of various nickel salts across human skin was relatively  minute. One percent or less of the nickel salts penetrated the stratum corneum at 96 hours, and less than 1% of the salts was retained. Retention in the stratum corneum was highest for the nitrate (0.95%) and lowest for the acetate (0.10%). Percent retentions in the stratum corneum of the chloride and sulfate salts were 0.18 and 0.56%,respectively.

 

The highest rate of permeation for all salts tested occurred within the first 24 hours. The chloride and acetate salts reached peak penetration

within 4 hours. Nickel nitrate peaked at ca. 8 hours, while nickel sulfate peaked after 12 hours post-application. Steady state was obtained after 24 hours for all the nickel salts tested. The permeability constants (standard deviation) of nickel salts across human stratum corneum in vitro were reported as:

nickel sulfate: 8.5 (5.5) cm/h x 10e-7

nickel chloride: 6.8 (1.2) cm/h x 10e-7

nickel nitrate: 5.2 (1.6) cm/h x 10e-7

nickel acetate: 5.2 (1.1) cm/h x 10e-7 

Applicant's summary and conclusion

Conclusions:
The study was focussed on the action of Ni2+ in solution and mainly driven by solubility. It can be adapted tonickel difluoride.
Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.

ROBUST SUMMARY DEVELOPED BY AN INDEPENDENT REVIEWER.

 

Robust Summary for Tanojo et al. (2001):

Human skin was obtained from cadavers and the stratum corneum was prepared using a modification of the method of Tanojo et al (1997).

Heat-separated human stratum corneum sheets were placed in a continuous flow-through diffusion cell system maintained at 37 deg. C. Aqueous donor solutions of nickel salts (nitrate, sulfate, and chloride) were prepared containing 1% w/v Ni (10 mg/ml Ni2+). HPLC-grade water was used as the receptor fluid, which was pumped at a rate of 4-5 ml/hr through the receptor side of the diffusion cells. The receptor water was collected every 4 hours up to 96 hours.

Donor solutions were collected from each diffusion cell. The stratum corneum sheets were boiled in 10 ml of a 30% hydrogen peroxide solution for 4 hours and cooled. Analyses were conducted by ICP-MS. The percentage of Ni compound recovered from the applied dose was determined. The 96-h in vitro permeation profile of each nickel salt was plotted against time using Microcal Origin, and the permeability constant of each salt was calculated from the permeation rate during steady state. Data were analyzed using the paired Student t-test on Microcal Origin. 

 

The permeation of various nickel salts across human skin was relatively minute. One percent or less of the nickel salts penetrated the stratum corneum at 96 hours, and less than 1% of the salts was retained. Retention in the stratum corneum was highest for the nitrate (0.95%) and lowest for the acetate (0.10%). Percent retentions in the stratum corneum of the chloride and sulfate salts were 0.18 and 0.56%,respectively. 

 

The highest rate of permeation for all salts tested occurred within the first 24 hours. The chloride and acetate salts reached peak penetration  

within 4 hours. Nickel nitrate peaked at ca. 8 hours, while nickel sulfate peaked after 12 hours post-application. Steady state was  

obtained after 24 hours for all the nickel salts tested. 

 

The permeability constants (standard deviation) of nickel salts across human stratum corneum in vitro were reported as: 

nickel sulfate: 8.5 (5.5) cm/h x 10e-7 

nickel chloride: 6.8 (1.2) cm/h x 10e-7 

nickel nitrate: 5.2 (1.6) cm/h x 10e-7 

nickel acetate: 5.2 (1.1) cm/h x 10e-7