Phosphoric acid, mono- and di-C16-18 (even numbered) alkyl esters, salts with 2,2'-iminodiethanol

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Diethanolamine absorption, metabolism and disposition in rat and mouse following oral, intravenous and dermal administration

Author:

J. M. Mathews, C. E. Garnier, S. L. Black, H. B. Matthews

Year:

1997

Bibliographic source:

Xenobiotica 1997, 27, 733-746 - https://www.tandfonline.com/doi/abs/10.1080/004982597240316

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

Test material information

Constituent 1

Reference substance name:

2,2'-iminodiethanol

EC Number:

203-868-0

EC Name:

2,2'-iminodiethanol

Cas Number:

111-42-2

Molecular formula:

C4H11NO2

IUPAC Name:

2,2'-iminodiethanol

Test material form:

liquid

Radiolabelling:

yes

Remarks:

[14C]diethanolamine (DEA)

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male

Details on test animals or test system 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

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

Signs and symptoms of toxicity:

yes

Dermal irritation:

yes

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 absorption

Percutaneous absorption 1

Key result

Time point:

48 h

Dose:

8 mg/kg bw

Parameter:

percentage

Absorption:

27 %

Percutaneous absorption 2

Key result

Time point:

48 h

Dose:

81 mg/kg bw

Parameter:

percentage

Absorption:

58 %

Any other information on results incl. tables

Results

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 diethanolamine equivalents were present in liver, kidney, and to a lesser degree in heart, lung, and spleen.

Results details:

Table 1: Disposition of radioactivity 48 h after dermal application of[14C]DEA

	Percentage of dose
	8 mg/kg bw	23 mg/kg bw	81 mg/kg bw	15 mg/kg bw (i.v.; 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	-
not absorbed	59.2  ± 5.5	49.4 ± 8.8	24.8 ± 63.5	-

Table 2: Disposition of radioactivity 48 h after dermal application of[14C]DEA - Tissue/blood ratio

	Tissue/blood ratio
	8 mg/kg bw	23 mg/kg bw	81 mg/kg bw	15 mg/kg bw (i.v.; n = 4)
Tissues
Adipose	8.41 ± 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	8.3 ± 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 of diethanolamine occurred in liver. The primary route of excretion of diethanolamine was the urine. Tissue to blood ratio was found to be highest in liver, kidney, lung, heart and spleen.

Applicant's summary and conclusion

Conclusions:

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