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Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Skin absorption and per os administration of methanol in men.
Author:
Dutkiewicz, B. et al.
Year:
1980
Bibliographic source:
Int Arch Occup Environ Health 47: 81-88
Reference Type:
publication
Title:
Methanol
Author:
DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area
Year:
1999
Bibliographic source:
In: Occupational Toxicants: Critical Data Evaluation for MAK Values and Classification of Carcinogens (Greim, H., ed.), Wiley-VCH

Materials and methods

Type of study / information:
Methanol absorption rate through the human skin has been examined by the use of a modified direct method. The excretion of unchanged methanol with urine and exhaled air, after the absorption through the skin and administration "per os" of identical doses, were also examined .
Endpoint addressed:
basic toxicokinetics
dermal absorption
Principles of method if other than guideline:
The methanol absorption rate through the human skin and the excretion of unchanged methanol with urine and exhaled air, after the absorption through the skin and administration "per os" of identical doses, were examined .
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Details on study design:
The experiments were carried out on volunteers. A modification of the direct method has been applied to estimate liquid methanol absorption through the skin. The absorbed dose was calculated from the difference between the amount applied to the surface of the skin and the amount left after the exposure time (15 to 60 min). The amounts of methanol, 0.19 -0.21 cm³, applied on the surface of the skin equal to the area of the applicator (11.2cm²) were the smallest possible. A total of 22 experiments in six subjects have been carried out and the absorption rate was calculated in mg/cm²/min.

In two subsequent experiments the absorbed amount of methanol was calculated on the basis of the known surface on the skin of the hand (435-445 cm²) immersed in liquid methanol and at a known absorption rate determined previously. The exposure time was always 20min. The quantities ranged from 1.67-1.71 g making possible the quantitative determination of methanol in urine and in exhaled air after exposure.

The exhaled air samples were collected in amounts of 5-10dm³, in the periods of time: 0, 0.5, 1.0, 1.5, 2.0, 2.5, 4.0 and 5.0 h after the termination of exposure. Urine samples were collected every hour for 8 h after the termination of exposure. Six experiments (3 subjects) were carried out on oral methanol administration, and collection of exhaled air and urine samples were performed as given above. The applied doses were always 1.67g. A spectrophotometric method was employed for quantitative determination of methanol in water solutions and urine destillates. The background concentrations found in urine before exposure amounted to 1.9-2.3 mg/dm³.
Exposure assessment:
measured

Results and discussion

Results:
Methanol absorption rate values through human skin (foremarm, 15-60 min.) range from 0.131 to 0.241 mg/cm²/min, with an average value of 0.192 mg/cm²/min. The absorbed amounts were 22 mg after 15 min exposure and ranged to 130 mg after 60 min of exposure.

The excretion of unchanged methanol exhaled air, after absorption through skin and administration "per os" amounted to 271 mg (16.2 %) and 360 mg (21.6 %) of the absorbed dose (1.67 g), respectively. The amounts excreted with urine amounted to 2 and 5.73 mg, respectively.

It was estimated, that exposure of one hand to liquid methanol for only 2 min. would lead to the absorption of as much methanol (170 mg), as would be taken up by the lungs from an 8 h exposure to MAC of 50 mg/m³ (38 ml/m³).

Applicant's summary and conclusion