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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented and scientifically acceptable report of a study conducted to GLP.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2006

Materials and methods

Principles of method if other than guideline:
Methods are described in 7.1.1 Basic Toxicokinetics.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Acrylamide
EC Number:
201-173-7
EC Name:
Acrylamide
Cas Number:
79-06-1
Molecular formula:
C3H5NO
IUPAC Name:
prop-2-enamide
Details on test material:
1,2,3-13C acrylamide (CLM-813, Lot number 1185, 99% labeled) obtained from Cambridge Isotopes.
Radiolabelling:
yes

Test animals

Species:
other: Human volunteers
Strain:
other: Not applicable
Sex:
male
Details on test animals or test system and environmental conditions:
Details are given in 7.1.1.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Duration of exposure:
3 periods of 24 hours
Doses:
3.0 mg/kg
No. of animals per group:
5 human volunteers
Control animals:
yes
Remarks:
Human volunteers
Details on study design:
A 50% (wt/vol) solution of 13C3 AM was applied directly on the skin to a clean, dry, marked off, 24 cm2 (3 cm 3 8 cm) area on the volar forearm. After applying the appropriate amount of material, the liquid was evaporated to dryness using a commercial hair dryer and covered with a sterile gauze pad. After drying the AM solution, the tape which had been used to demark the area of application was removed and placed in a vial containing 20 ml of water. The water (dermal dam solution) was analyzed for AM by high-performance liquid chromatography (HPLC). The site of application was covered with gauze for 24 h at which time the gauze was removed and the area was washed with 1000 ml of water. The recovered wash water was analyzed by HPLC for AM. Dermal applications alternated between left and right arms, starting with the subject’s dominant arm. Blood was collected immediately prior to compound administration and 24, 48, 72 and 96 hours later (immediately prior to administration of the second and third doses, after gauze removal and prior to leaving the clinic). Hormone blood samples were drawn immediately prior to compound administration, after 24 hours and on day 5 when the volunteers left the clinic.

Results and discussion

Signs and symptoms of toxicity:
yes
Remarks:
One individual demonstrated dermal hypersensitivity to acrylamide.
Dermal irritation:
no effects
Absorption in different matrices:
None used.
Total recovery:
83.94%
Percutaneous absorption
Dose:
3.0 mg/kg
Parameter:
percentage
Absorption:
6 %
Remarks on result:
other: 24 hours
Conversion factor human vs. animal skin:
No coversion factor since this was a human study.

Applicant's summary and conclusion

Conclusions:
In this well conducted study, designed to maximise absorption, the recovery of the labelled material was very satisfactory at 83.9%. The study demonstrated that dermal absorption in humans is slow. Only 4.5% of the applied dose was absorbed from an occluded patch on the forearm over a 24 hour period which equates to less than 0.2% absorption per hour.