dichloromethane; methylene chloride

Dermal absorption

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:

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

Data source

Reference

Reference Type:

publication

Title:

A physiological pharmacokinetic model for dermal absorption of vapors in the rat

Author:

McDougal JN, Jepson GW, Clewel III HJ, MacNaughton MG, Andersen ME

Year:

1986

Bibliographic source:

Toxicol Appl Pharmacol 85: 286-294

Materials and methods

Principles of method if other than guideline:

Rats were exposed for 4 h by inhalation, and DCM was measured in blood samples. The total amount DCM absorbed through the skin during the exposure was calculated based on blood concentrations during and at the end of the exposure using a physiological model (Andersen et al., 1984).

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dichloromethane

EC Number:

200-838-9

EC Name:

Dichloromethane

Cas Number:

75-09-2

Molecular formula:

CH2Cl2

IUPAC Name:

dichloromethane

Test material form:

not specified

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

Male Fischer 344 rats (190 to 230 g) were used for all experiments. Surgical implantation ofindwellingjugular cannulas and clipping of the fur were accomplished under ketamine/xylazine anesthesia 24 hr prior to exposure.

Administration / exposure

Type of coverage:

other: vapor exposure

Vehicle:

unchanged (no vehicle)

Duration of exposure:

4 h

Doses:

Concentrations were: 30000, 60000 and 100000 ppm (106, 212, and 353 g/m3).

No. of animals per group:

6

Control animals:

no

Details on study design:

A specially designed dermal vapor absorption chamber prevented inhalation of vapor by providing clean filtered breathing air through a latex face mask. Design and operation of this chamber as well as blood concentrations measured during exposures were described previously (McDougal et al., 1985). On the day ofthe exposures, six rats were placed in the chamber and exposed for 4 h. Blood samples (0.1 ml) were collected before and during the DCM vapor exposures via the indwelling jugular cannula, extracted with heptane, and analyzed for DCM with electron capture detection after gas chromatographic separation.

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

Measured DCM blood concentrations increased with an increase in exposure concentration (Fig. 2). Blood concentrations rose rapidly and were nearly at steady state at 1 hr in all but the 100,000-ppm exposure, which took longer. Blood concentrations at the
higher exposure concentrations were greater than expected based on the 30,000-ppm exposure.
The amount and rate of penetration of vapors through the skin was proportional to exposure concentration (Fig. 3). Mean permeability constant was 0.28 cm/h.
Predictions from the skin exposure model were in good agreement with the DCM exposure concentrations (Fig. 3). Calculated flux data are indicated in Table 4 and are proportional to concentration.

Total recovery:

Not applicable

Percutaneous absorption

Percutaneous absorption 1

Time point:

4 h

Dose:

30000 ppm

Parameter:

rate

Absorption:

0.031 mg cm-2 h-1

Percutaneous absorption 2

Time point:

4 h

Dose:

60000 ppm

Parameter:

rate

Absorption:

0.052 mg cm-2 h-1

Percutaneous absorption 3

Time point:

4 h

Dose:

100000 ppm

Parameter:

rate

Absorption:

0.103 mg cm-2 h-1

Percutaneous absorption 4

Time point:

4 h

Dose:

30000, 60000, 100000 ppm

Parameter:

other: mean permeability constant

Absorption:

0.28 cm/h

Applicant's summary and conclusion

Conclusions:

The vapour absorption rate of DCM in rats during exposure at 30000, 60000 or 100000 ppm (106, 212 or 353 g/m3) was 0.031, 0.052 and 0.103 mg/cm2/h, respectively. The mean permeability constant was 0.28 cm/h.