N,N-dimethylisopropylamine

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Skin absorption of the industrial catalyst dimethylethylamine in vitro in guinea pig and human skin, and of gaseous dimethylethylamine in human volunteers

Author:

Lundh T, Bowan A, Akesson B

Year:

1997

Bibliographic source:

Int. arch Occup Environ Health 70, 309-313

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Skin absorption of dimethylethylamine in vitro was determined with human and guinea pig skin samples.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Ethyldimethylamine

EC Number:

209-940-8

EC Name:

Ethyldimethylamine

Cas Number:

598-56-1

Molecular formula:

C4H11N

IUPAC Name:

N,N-dimethylethanamine

Details on test material:

- Name of test material (as cited in study report): dimethylethylamine
- Purity: 99%
- Source: Janssen Chemical. Geel. Belgium

Radiolabelling:

no

Test animals

Species:

guinea pig

Strain:

other: albino

Details on test animals or test system and environmental conditions:

Fresh full-thickness albino guinea-pig skin was used (mean 640 g, obtained from Sahlin's Forsoksdjursfarm, Malmo, Sweden). The skin was mounted in Teflon flow-through cells (Vangard International, Neptune, N.J.; Bronaugh 1991). Before exposure, the skin was left to acclimatize for 1 h.

Administration / exposure

Type of coverage:

open

Vehicle:

other: water or isotonic saline solution

Doses:

100 µl of 1% solution (0.67mg/ml)

Control animals:

no

Details on in vitro test system (if applicable):

DMEA was diluted to 1% (i.e. 0.67 mg/ml) with water or isotonic saline solution, 100 µl of the solution being applied to the skin surface.
The perfusion medium, Hanks balanced salt solution was supplied at a flow rate of 1.5 ml/h using a peristaltic pump (Alitea, Stockholm. Sweden) to ensure sink conditions.
Using a fraction collector (Gilson 202. France). the perfusion fluid was collected at 2h-intervals for 48 h in vials containing 100 µl 1 M hydrochloric acid (HCl 37% Merck, Darmstadt, Germany).
Steady-state flux (Jss) was calculated from the slope of the linear portion of the plot of cumulative amount penetrated /cm² versus time for each cell. The permeability coefficient (Kp) at apparent steady state or at the peak absorption rate was calculated according to Fick's law as: Kp =Jss/C where Kp is the permeability coefficient (cm/ h), Jss the steady-state flux (mg/cm² x h) and C the concentration of penetrating chemical in the medium (mg/cm²).

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

DMEA penetrated guinea pig skin.
The median Jss and Kp were 0.009 mg/cm2 x h and 0.001 cm/h, respectively.
No DMEAO could be found in the perfusion medium.

Percutaneous absorption

Dose:

1%

Remarks on result:

other: Kp= 0.001cm/h for guinea pig skin

Any other information on results incl. tables

The steady-state flux permeability coefficient (Kp) and the lag-time obtained in the in vitro experiments. The respective medians from each experiment are based on data obtained from six flow-through cells
	Experiment n°	Jss (mg/cm² x h)		Kp (cm/h)		Lag-time (h)
		Mean	Range	Mean	Range	Mean	Range
Guinea-pig skin	1	0.008	(0.008-0.011)	0.001	(0.001-0.002)	7	(3 9)
	2	0.005	(0.004-0.009)	0.001	(0.001-0.001)	Neg b
	3 a	0.025	(0.018-0.027)	0.004	(0.002-0.004)	3	11-5)
	4 a	0.009	(0.006-0.023)	0.002	(0.001-0.003)	8	(6-10)
a DMEA diluted with isotonic saline solution
b Negative, the curve shape did not allow lag-time calculation

Applicant's summary and conclusion

Executive summary:

The aims of the study was to assess the skin uptake of dimethylethylamine (DMEA) in vitro from water solutions by fresh guinea-pig specimens. Specimens were analysed by gas chromatography using a nitrogen-sensitive detector. DMEA, diluted with water or isotonic saline solution was applied to fresh guinea-pig skin, mounted in Teflon flow-through cells with a perfusion fluid flow rate of 1.5 ml/h, samples being collected at 2-h intervals for 48 h. DMEA penetrated guinea-pig . The median steady-state flux and permeability coefficient (Kp) values, were 0.009 mg/cm2 x h and 0.001 cm/h, respectively.