4-methylpentan-2-one

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:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Percutaneous uptake and kinetics of methyl isobutyl ketone (MIBK) in the guinea pig

Author:

Hjelm EW, Boman A, Fernström P , Hagberg M and Johanson G

Year:

1991

Bibliographic source:

Toxicol Letters, 56, 79–86

Materials and methods

Principles of method if other than guideline:

Quantitative estimation of the percutaneous uptake rate and toxicokinetics of MIBK in the guinea-pig

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

4-methylpentan-2-one

EC Number:

203-550-1

EC Name:

4-methylpentan-2-one

Cas Number:

108-10-1

Molecular formula:

C6H12O

IUPAC Name:

4-methylpentan-2-one

Details on test material:

- Supplier: Aldrich
- Purity: 99.7%

Radiolabelling:

no

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: J.A. Sahlin, Malmb, Sweden
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: Makrolon cages
- Individual metabolism cages: no data
- Diet (ad libitum): standard pelleted food for guinea-pig and rabbit breeding (Ewos, S6dertlje, Sweden)
- Water (ad libitum): tap water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

up to the end of the experiment

Doses:

1 ml

No. of animals per group:

8

Control animals:

no

Details on study design:

The hair on the back of the animal was clipped and one glass cylinder with an internat area of 3.14 cm2 was glued with cyanoacrylate to the skin. At 150-190 min after termination of the infusion a `blank' blood sample was collected and the cylinder on the back of the animal was then filled with 1 ml of neat MIBK and subsequently sealed by gluing a glass lid on top of it. Blood samples were collected at 5, 10 and 15 min and then every 15 min until 150 min after onset of exposure.

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Percutaneous absorption

Remarks on result:

other: Percutaneous uptake rate in guinea pigs exposed epicutaneously to MIBK peaked at 10 to 45 minutes after the onset of a 150-minute exposure; the maximum uptake rate ranged from 0.11 to 2.0 µmol/min/cm and averaged 1.1 µmol/min/cm.

Any other information on results incl. tables

During epicutaneous exposure the concentration of MIBK in blood rose rapidly and reached a maximum concentration after 10-45 min and then started to decline in spite of continuons exposure (Fig. 1). Large individual variations in blood concentrations were observed during epicutaneous exposure; the maximum concentration ranged between 7 and 55 µmol/l (Table II). The maximum percutaneous uptake rate for all animals averaged 1.1 (range 0.15-2.2) µmol.min-1.cm-2 and was reached 10-45 min after onset of exposure. The mean uptake rate 15-75 min after onset of exposure was 0.86 (range 0.11-2.0) µmol.min-1.cm-2. Later during the exposure, at 75-135 min, the uptake rate decreased to 0.56 (range 0.084-1.5) µmol.min-1.cm². This decrease, which was observed in all experiments, averaged 34% (range 20-47%) (Table II).

Applicant's summary and conclusion

Executive summary:

The percutaneous uptake rate in guinea pigs exposed epicutaneously to MIBK peaked at 10 to 45 minutes after the onset of a 150-minute exposure; the maximum uptake rate ranged from 0.11 to 2.0 µmol/min/cm and averaged 1.1 µmol/min/cm².