Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Thoroughly conducted study and well reported. Raw data and GLP status not reported.

Data source

Reference
Reference Type:
publication
Title:
In vitro skin penetration of monoethanolamine and diethanolamine using excised skin from rats, mice, rabbits, and humans
Author:
Sun JD
Year:
1996
Bibliographic source:
Journal of Toxicology, Cutaneous and Ocular Toxicology, 15(2), 131-146

Materials and methods

GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Monoethyanolamine
- Analytical purity: 98.8%
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
other: rats, mice, rabbits, human
Strain:
other: CD rats, CD-1 mice, New Zealand white rabbits
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Rats and mice: Charles River Laboratories, Rabbit: HRP Inc, Human skin: mammoplasty patients in the University of Pittsburg Hospital system
- Age at study initiation: Rats: 10 weeks, mice: 6 weeks, Rabbits: 11-12 weeks
- Housing: Rats: 2/cage, rabbits: 3/cage in stainless steel wire mesh cages, mice: 4-5/cage in plastic shoebox cages
- Diet (e.g. ad libitum): Pelleted ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Duration of exposure:
6 hours
Doses:
- Nominal doses: 4 mg/cm²
- Dose volume: 7 µg/l undiluted, 32 µg/l aqueous
- Rationale for dose selection: Highest doses in dermal developmental toxicity studies
No. of animals per group:
1
Control animals:
yes
Details on study design:
APPLICATION OF DOSE: 14C MEA was applied to skin discs as either an undiluted liquid or as an aqueous solution at a target dose of 4 mg/cm³. for undiluted 14C MEA, the dose volume applied to skin discs was approximately 7 µg/l. For the applications of aqueous solution of 14C MEA, the dose volume was approximately 32 µg/l. These dose volumes covered the entire exposed surface of the skin (1.77 cm²).

VEHICLE
- Justification for use and choice of vehicle (if other than water): 14C ethanol
- Amount(s) applied (volume or weight with unit):250 µg/l
- Concentration (if solution):25% aqueous solution

TEST SITE
- Preparation of test site: Fur was clipped from the dorsal trunk in the thoracic region and a section of clipped skin was removed and placed in a petri dish.
- Area of exposure: 1.77 cm²
- Type of cover / wrap if used: 2 ply gauze

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: no

REMOVAL OF TEST SUBSTANCE
- Washing procedures and type of cleansing agent: Water wetted cotton swabs
- Time after start of exposure: 6 hours

SAMPLE PREPARATION
- Storage procedure:
- Preparation details:

ANALYSIS
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC): LSS
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin:mammoplasty patients
- Ethical approval if human skin:
- Preparative technique: maintained in minimum essential medium and 25 nM HEPES buffer with penicillin/streptomycin as antimicrobial agents

PRINCIPLES OF ASSAY
- Receptor fluid: MEM medium
- Flow-through system: Dynamic flow through system

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
Percentage of dose penetrating the skin
Undiluted MEA
- Effluents: Rat 5.98±0.68: Mouse 16.92±1.67 : Rabbit 8.66±3.08 : Human 0.61±0.18
- Unabsorbed dose: Rat 44.58±1.85 : Mouse 42.32±0.54 : Rabbit 34.69±0.86 : Human 51.64±3.28
- Skin combustion: Rat 9.40±0.91 : Mouse 4.85±0.35 : Rabbit 7.15±0.71 : Human 5.93±0.78
- Apparatus rinse: Rat 0.69±0.33 : Mouse 1.63±0.23 : Rabbit 0.71±0.17 : Human 0.19±0.07

Aqueous MEA
- Effluents: Rat 1.32±0.54: Mouse 24.79±2.68 : Rabbit 1.87±0.43 : Human 1.11±0.29
- Unabsorbed dose: Rat 62.32±0.37 : Mouse 59.47±2.68 : Rabbit 75.43±1.09 : Human 61.87±2.21
- Skin combustion: Rat 8.47±0.18 : Mouse 4.00±0.51 : Rabbit 4.69±0.29 : Human 6.44±0.99
- Apparatus rinse: Rat 0.38±0.20 : Mouse 2.48±0.29 : Rabbit 0.36±0.05 : Human 0.24±0.05
Total recovery:
Percentage of total dose
Undiluted MEA
- Total recovery: Rat 60.65±1.75 : Mouse 65.72±1.60 : Rabbit 51.21±1.74 : Human 58.37±2.80

Aqueous MEA
- Total recovery: Rat 72.48±0.90 : Mouse 90.75±0.39 : Rabbit 82.35±0.93 : Human 69.66±1.49
Percutaneous absorptionopen allclose all
Parameter:
percentage
Absorption:
5.98 %
Remarks on result:
other: Undiluted Rat
Parameter:
percentage
Absorption:
16.92 %
Remarks on result:
other: Undiluted Mouse
Parameter:
percentage
Absorption:
8.66 %
Remarks on result:
other: Undiluted Rabbit
Parameter:
percentage
Absorption:
0.61 %
Remarks on result:
other: Undiluted Human
Parameter:
percentage
Absorption:
1.32 %
Remarks on result:
other: Aqueous Rat
Parameter:
percentage
Absorption:
24.79 %
Remarks on result:
other: Aqueous Mouse
Parameter:
percentage
Absorption:
1.87 %
Remarks on result:
other: Aqueous Rabbit
Parameter:
percentage
Absorption:
1.11 %
Remarks on result:
other: Aqueous Human

Applicant's summary and conclusion

Conclusions:
The permeation of undiluted MEA through animal skin was between 5 and 15 times greater than through human skin, with mouse skin showing the highest degree of permeability.There is generally greater skin permeability of aqueous MEA. Water may act as a carrier of these alkanolamines through skin and facilitate their penetration.
Executive summary:

Rat, mouse, rabbit and human skin were administered nominal doses of 4 mg/cm2 of undiluted or aqueous MEA in vitro.  Mean dermal absorption values after 6 hours were 5.98,16.92, 8.66 and 0.61% (undiluted MEA) and 1.32, 24.79, 1.87 and 1.11% (aqueous MEA), respectively for rat, mouse, rabbit and human skin. It is appropriate to utilise the highest dermal absorption value in human skin to be conservative in risk assessment. Therefore, a dermal absorption value of 1.11% in aqueous MEA has been identified for human skin.