Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Currently viewing:

Administrative data

direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study published in a peer-reviewed journal, according to scientific standards, well-documented, but no individual data reported.
Reason / purpose:
reference to same study

Data source

Reference Type:
Relationship of pKa and acute skin irrritation in humans
Berner B, Wilson DR, Guy RH, Mazzenga GC, Clarke FH & Maibach HI
Bibliographic source:
J. Toxicol. - Cut. & Ocular Toxicol., 1989, 9(2), 481-492

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
skin irritation / corrosion
Test guideline
no guideline followed
Principles of method if other than guideline:
Skin irritation in human female volunteers was assessed before and after 1-day exposure to test substance-loaded hydrogel discs, and again 24 hours later, by assessment of erythema, edema, blood flow (by laser Doppler velocimetry), color, and primary irritation index.
GLP compliance:

Test material

Details on test material:
- Name of test material (as cited in study report): salicylamide
- Substance type: pure test substance
- Physical state: solid, powder, melting point 140°C
- Analytical purity: analyzed by HPLC, no extraneous peaks observed
- Impurities (identity and concentrations): none detected by HPLC
- Skin irritancy tested in rabbits: non-irritant


Type of population:
- Number of subjects exposed: 16
- Sex: female
- Age: 35 - 45 years
- Race: 10 hispanic (olive-complected skin), 5 white (type II skin), 1 white/Polynesian (slightly olive skin)
- Demographic information: no data
- Known diseases: none
- Other: reasonably clear backs with no or few comedones, moles, and freckles
Ethical approval:
confirmed, but no further information available
subjects consented to the study
Route of exposure:
Reason of exposure:
Exposure assessment:
Details on exposure:
Hydroxyethyl methacrylate (HEMA) hydrogel films were prepared by polymerization from HEMA, carefully extracted to remove free monomer, and cut into 1 cm2 discs, which were loaded with the test substance by soaking in a saturated solution in ethanol/water (7:3) and dried. Immediately before application, discs were soaked in a saturated aqueous solution of the test material, and applied to the scapular region of the test subjects. The loaded test discs were occluded with an ethylene vinyl acetate membrane and secured with tape.
Loading of discs: determined by weight difference of the disc before and after loading, checked by extraction into a known volume of ethanol/water and analysis. Percent uptake per dry weight: 36.6 +- 5.9
- Urine analysis: no
- Haematology: no
- Lung function parameters: no
- Other: Skin erythema, edema (both graded by standard 0-4 visual scale, enhanced by scale 0.5 for borderline reaction), blood flow (by laser Doppler velocimetry), color, and primary irritation index, determined on treated skin area before exposure, after 1 day (at end of exposure) and after 2 days.

Results and discussion

Clinical signs:
Results of examinations:
- Erythema: statistically indistinguishable from control at 24 and 48 hours
- Edema: statistically indistinguishable from control at 24 and 48 hours
- Color: statistically indistinguishable from control at 24 and 48 hours
- Laser Doppler velocity (LDV): statistically indistinguishable from control at 24 and 48 hours
- Primary Irritation index (PII): statistically indistinguishable from control at 48 hours

Any other information on results incl. tables

Mean irritation scores:

Hours Erythema Edema Color LDV PII
Salicylamide 24 0.05 ± 0.15 0.03 ± 0.12 5.3 ± 2.2 44 ± 15
Water control 24 0.03 ± 0.18 0.03 ± 0.18 5.1 ± 1.5 44 ± 13
Salicylamide 48 0.08 ± 0.22 0.00 ± 0.00 4.8 ± 1.6 43 ± 11 0.08 ± 0.18
Water control 48 0.06 ± 0.21 0.00 ± 0.00 4.7 ± 1.4 42 ± 12 0.08 ± 0.24

Applicant's summary and conclusion

Under the conditions of the study, human volunteers treated with salicylamide were not significantly different from a water control in any of the observed variables.