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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented following scientific principles

Data source

Reference
Reference Type:
publication
Title:
In vivo percutaneous absorption of chemicals: a multiple dose study in rhesus monkeys
Author:
Bucks DAW, Hinz RS, Sarason R et al
Year:
1990
Bibliographic source:
Chem. Toxic. 28(2), 129-132

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The chemical was administered in a small volume to a lightly clipped area of the abdomen on a single- or multiple-dose exposure. Then, percutaneous absorption and urinary elimination were investigated.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): salicylic acid
- Radiochemical purity (if radiolabelling): greater than 95 %
- Specific activity (if radiolabelling): 27 mCi/mM
- Locations of the label (if radiolabelling): 14C-carboxyl
Radiolabelling:
yes

Test animals

Species:
monkey
Strain:
other: macaca mulatta (rhesus)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: California Primate Research Center (davis, CA)
- Age at study initiation: 7+/-3 yr
- Weight at study initiation: 5 +/- 2 kg
- Fasting period before study: data not available
- Housing: data not available
- Individual metabolism cages: no data
- Diet : ad libitum- Water : ad libitum
- Acclimation period: data not available

ENVIRONMENTAL CONDITIONS
data not available

Administration / exposure

Type of coverage:
not specified
Vehicle:
acetone
Duration of exposure:
14 days
Doses:
Females: 4 mg/cm²
No. of animals per group:
4
Details on study design:
TEST SITE
- Area of exposure: a lightly clipped area of the abdomen
- % coverage: no data
- Type of wrap if used: no data
- Time intervals for shavings or clipplings: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with soap and water (for single-dose experiments only)
- Time after start of exposure: 24hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mg/cm2

VEHICLE- Justification for use and choice of vehicle (if other than water): no data

USE OF RESTRAINERS FOR PREVENTING INGESTION:
yes (in the multiple-application experiments)

PHARMACOKINETIC STUDY (absorption, excretion)
- Tissues and body fluids sampled : urine
- Time and frequency of sampling: day 1: 0-4, 4-8, 8-12 and 12-24 hr; day 2-7: urine for each 24-hr period was combined

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified

Any other information on results incl. tables

Penetration rate:

Single application: 59 +/-32 %

14 -day application (cumulative absorption):

1st day: 67 +/- 17 %

8th day: 78 +/- 18 %

Salicylic acid was absorbed across the skin. The amount penetrating from a single application could not be distinguished from that absorbed following a 14-day multiple application protocol

Applicant's summary and conclusion

Conclusions:
No significant change in percutaneous absorption from that following the initial dose was observed following the eighth daily dose of a 14-day multidose regimen for each of the three penetrants considered. Cumulative percentage of 14C dose absorbed through the skin for SA: single dose : 59 +/- 32 % multiple dose : 1st one : 67 +/- 17 % - 8th dose : 78 +/- 18.
Executive summary:

In a percutaneous absorption (Bucks et al., 1990), salicylic acid was administered at a surface dose of 4 mg/cm2to a lightly clipped area of the abdomen either in a single-dose exposure or in a multiple-dose exposure. To quantify absorption, urine was collected for 7 days after dosing. Percutaneous absorption was observed. The amount penetrating from a single application (59 +/-32 %) could not be distinguished from that absorbed following either the first (67 +/- 17 %) or the eighth (78 +/- 18 %) daily dose of a 14-day multiple application protocol. Thus, under the conditions used, measurement of percutaneous absorption after a single application can be predictive of permeation when multiple skin contacts occur.