Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to test guidelines and in accordance with GLP

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986
Reference Type:
publication
Title:
Unnamed
Year:
2007

Materials and methods

Principles of method if other than guideline:
This study was conducted to determine the relative dermal bioavailability (absorption), distribution, metabolism, and excretion (ADME) of diisopropanolamine (DIPA). Groups of 4 female Fischer 344 rats received a dermal application of 19.5 mg/ kg 14C-DIPA in acetone to an area of 1 cm2 on the back and covered with a bandage. Time-course blood and excreta were collected and radioactivity determined. Urine was analyzed for DIPA and monoisopropanolamine (MIPA).
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): Diisopropanolamine
- Analytical purity: 99 %
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Inc. (Kingston, NY)
- Age at study initiation: 10 weeks
- Weight at study initiation: 148–162 g
- Housing: two per cage
- Individual metabolism cages: yes/no
- Diet: Purina Certified Rodent Chow #5002 (Ralston Purina Co.,) ad libitum
- Water: ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2°C
- Humidity (%): 40–60 %
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
acetone
Duration of exposure:
48 h
Doses:
19.5 mg/kg bw
No. of animals per group:
4
Control animals:
no
Details on study design:
TEST SITE
- Preparation of test site: shaved
- Area of exposure: 1 cm2
- Type of cover / wrap if used: 4 cm2 piece of Teflon and secured in place with Conform adhesive bandages


SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes: each rat was fitted with a rodent jacket


SAMPLE COLLECTION
- Collection of blood: 0.5, 1, 2, 4, 6, 12, 24, 36 and 48 h post-dosing
- Collection of urine and faeces: 6, 12, 24 and 48 h post-dosing (urine); feces: at 12 h intervals
- Collection of expired air: 12 h intervals


ANALYSIS
- Method type(s) for identification: Liquid scintillation counting

Results and discussion

Percutaneous absorption
Dose:
19.5 mg/kg bw
Parameter:
percentage
Absorption:
ca. 20 %
Remarks on result:
other: 48 h
Remarks:
Total recovery: 69%, of which 26% was recovered from protective appliciances and 24% from the surface of the dosed skin

Any other information on results incl. tables

The total recovery of the dermally applied dose was 69.2 ± 17.0%. The recovery of the applied radioactivity from 3 out of 4 rats was between 71% and 80%; recovery in one of the rats was only 48%. Most of the administered radioactivity was recovered from the protective appliances (Teflon patch, template, bandage, and jacket) accounting for 25.7 ± 11.2% and from the surface of the dosed skin (23.7 ± 4.5%). At the end of the study (48 h post-application), 3.5 ± 3.5% of the dose was found in skin remote from the site of the dosing with levels in 2 of 4 rats 0.5% and the other 2 between 5% and 8% of the dose. Concentration of 14C-DIPA-derived radioactivity was 0.1% in liver and kidney and 0.01% in fat. A total of 1.1 ± 0.4% of the applied dose was found in carcass. The dermally applied DIPA was not volatile or metabolized to CO2; 0.2% of the dosed radioactivity was trapped in charcoal or monoethanolamine:1-methoxy-2-propanol solution. A total of 14.6% of the applied radioactivity was found in excreta (urine + feces + final cage wash). Consistent with the intravenous data, urine was the major route for the excretion of 14C-DIPA constituting 99% of the total excretion (urine + final cage wash + feces), fecal elimination of 14C-DIPA was 0.2% or 1.2% of the total radioactivity recovered in excreta.

Applicant's summary and conclusion