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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Diethanolamine absorption, metabolism and disposition in rat and mouse following oral, intravenous and dermal administration
Author:
Mathews JM, et al.
Year:
1997
Bibliographic source:
Xenobiotica, 27, 733-746

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The disposition of [14C]diethanolamine ( DEA) was determined in mouse after dermal and intravenous administration.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diethanolamine (DEA)
- Analytical purity: 99%
- Radiochemical purity (if radiolabelling): >97%
- Locations of the label (if radiolabelling): randomly labelled
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories (Raleigh, NC, USA)
- Age at study initiation: adult
- Weight at study initiation: 21-29 g
- Housing: individual in glass metabolism chambers permitting separate collection of CO2, urine and faeces
- Individual metabolism cages: yes
- Diet: and furnished Purina Rodent C. ad libitum
- Water: ad libitum

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
ethanol
Doses:
dermal dosing studies: single doses of 8, 23, 81 mg/kg
No. of animals per group:
dermal dosing studies: 4-5 mice (as further indicated)
Control animals:
no
Details on study design:
Dermal dose formulations contained from 6 to 20 mCi, an appropriate amount of unlabelled DEA and 95% ethanol for a total dose volume of 15 µl per dose. Dermal doses were applied to an area of skin (1 cm²) from which hair had been clipped the previous day. After dosing, a hemispherical dome of wire mesh (histology tissue capsule) was glued over the dose area with cyanoacrylate adhesive to serve a non-occlusive protective applicance.

Results and discussion

Absorption in different matrices:
Dermal doses ranging from 8-80 mg/kg bw were absorbed at levels between 25 and 60% within 48 hours of exposure. Absorption increased dose dependently.
The distibution pattern observed following dermal application in mice was similar to the data obtained for the rat. The highest concentrations of DEA equivalents were present in liver, kidney, and to a lesser dregree in heart, lung, and spleen. The highest tissue accumulation occurred in liver.
Percutaneous absorptionopen allclose all
Dose:
8 mg/kg bw
Parameter:
percentage
Absorption:
27 %
Remarks on result:
other: 48 h
Dose:
81 mg/kg bw
Parameter:
percentage
Absorption:
58 %
Remarks on result:
other: 48 h

Any other information on results incl. tables

Results summary:

Absorption:

Dermal doses ranging from 8 -80 mg/kg bw were absorbed at levels between 25 and 60% within 48 hours of exposure. Absorption increased dose dependently.

Distribution:

The distribution pattern observed following dermal application application in mice was similar to the data obtained for the rat. The highest concentrations of DEA equivalents were present in liver, kidney, and to a lesser degree in heart, lung, and spleen.

Results details:

Disposition of radioactivity 48 h after dermal application of[14C]DEA

Percentage of dose

8 mg/kg (n=5)

23 mg/kg (n=5)

81 mg/kg (n=4)

15 mg/kg iv (n=4)

Absorbed

Tissues

13.2 ± 3.5

18.9 ± 4.5

37.0 ± 5.6

54.1 ± 2.1

urine

7.5 ± 2.4

10.4 ± 2.7

16.4 ± 4.8

25.5 ± 5.0

Faeces

2.1 ± 0.7

1.4 ± 0.6

2.6 ± 2.2

3.0 ± 0.9

Dose site skin

4.0 ± 0.7

3.1 ± 0.5

2.2 ± 0.6

-

Total

26.8 ± 6.6*

33.8 ± 7.2

58.1 ± 4.9

-

unabsorbed

59.2 ± 5.5

49.4 ± 8.8

24.8 ± 63.5

-

Tissue/blood ratio

Tissues

adipose

8.43 ± 1.89

8.96 ± 4.52

10.8 ± 7.2

16.2 ± 5.9

brain

6.03 ± 0.95

6.87 ± 0.72

7.04 ± 0.9

8.30 ± 1.44

heart

23.3 ± 4.9

25.2 ± 4.9

18.7 ± 2.5

23.0 ± 4.2

kidney

107 ± 9

123 ± 6

104 ± 24

105 ± 14

liver

138 ± 2

129 ± 2

118 ±15

102 ± 19

lung

43.3 ± 4.0

52.0 ± 6.3

48.4 ± 5.6

50.4 ± 6.9

muscle

9.97 ± 1.91

8.88 ± 1.40

8.9 ± 1.10

10.69 ± 1.8

skin

11.0 ± 4.30

6.72 ± 1.29

8.56 ± 0.38

8.34 ± 0.98

spleen

26.7 ± 4.2

27.1 ± 5.2

29.2 ± 2.70

30.0 ± 2.7

In mice, the highest tissue accumulation occurred in liver. The primary route of excretion was the urine.
Tissue to blood ratio was found to be highest in liver, kidney, lung, heart and spleen.

Applicant's summary and conclusion