Reaction mass of 2-methylbutyl acetate and pentyl acetate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 Jan - 3 Feb 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: The recommendations of the OSHA (TSCA, Section 4, ITC) published in the Federal Register (1999), which references a protocol Bronaugh R L and Collier S W (1991). Protocol for In vitro Percutaneous Absorption studies. In Vitro Percutaneous Absorption : Pr

Principles of method if other than guideline:

Study was conducted prior to acceptance of actual guidelines but followed intent of the guidelines

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 2-methylbutyl acetate and pentyl acetate

EC Number:

908-918-1

Molecular formula:

Unspecified

IUPAC Name:

Reaction mass of 2-methylbutyl acetate and pentyl acetate

Details on test material:

- Analytical purity: 99.8%

Radiolabelling:

no

Test animals

Species:

human

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Extraneous tissue was removed from human whole skin samples obtained post mortem. The skin samples were immersed in water at 60°C for 40-45 seconds and the epidermis teased away from the dermis. Each epidermal membrane was given an identifying number and stored frozen on aluminium foil until required for use.

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hr

Doses:

100ul/cm2

No. of animals per group:

5

Control animals:

no

Details on study design:

See other sections

Details on in vitro test system (if applicable):

The primary amyl acetate isomer mixture was applied undiluted to the skin membranes at a dose rate of 100 µl/cm2 and left unoccluded for the duration of the exposure period (24h).
At recorded intervals (pre-treatment, 0.17,0.5, 1,2, 3,4,6, 8, 10, 12, 16, 20 and 24h) 0.5ml samples of the receptor fluid were taken for analysis by GLC. The volume of fluid in the receptor chamber was maintained by the addition of 0.5ml fresh receptor fluid to the chamber immediately after the removal of each sample.
Iso-hexane (0.5ml) was added to the receptor fluid samples and the whole shaken vigorously for 30 seconds. Where emulsions between the two phases occurred, 50 µl of a 10% sodium chloride solution was added. After the two phases separated, the lower aqueous phase was carefully drawn off using a syringe and discarded. The remaining iso-hexane extract was left in the vial and analysed for the amyl acetate isomers.

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

The absorption profiles for both isomers of amyl acetate were similar and the absorption rates were essentially constant after the first 6h of exposure. The 2-methylbutyl acetate isomer was absorbed at a rate of 47.8ug/cm2/h (Kp = 1.56 x 10(-4) cm/h), while the pentyl acetate isomer was absorbed at a somewhat faster rate of 123ug/cm2/h (Kp = 2.16 x 10(-4)cm/h).

Conversion factor human vs. animal skin:

study conducted with human skin

Applicant's summary and conclusion

Conclusions:

The absorption rates for both isomers of amyl acetate were essentially constant after the first 6h of exposure. The 2-methylbutyl acetate isomer was absorbed at a rate of 47.8μg/cm2/h (Kp = 1.56 x 10(-4) cm/h), while the pentyl acetate isomer was absorbed at a rate of 123μg/cm2/h (Kp = 2.16 x 10(-4) cm/h).

Executive summary:

The absorption of primary amyl acetate isomers from a 35:65 mix of 2-methylbutyl acetate and pentyl acetate has been measured in vitro through human epidermis. The primary amyl acetate mixture was applied undiluted at a rate of 100μl/cm² and left occluded throughout the entire exposure period (24h).

The absorption rates for both isomers of amyl acetate were essentially constant after the first 6h of exposure. The 2-methylbutyl acetate isomer was absorbed at a rate of 47.8μg/cm²/h (Kp = 1.56 x 10^-4 cm/h), while the pentyl acetate isomer was absorbed at a rate of 123μg/cm²/h (Kp = 2.16 x 10^-4 cm/h).

The results obtained in this study indicate that the 2-methylbutyl acetate and pentyl acetate isomers are moderately well absorbed through human epidermis when compared with the absorption rates of other penetrants measured using this in vitro technique (Dugard et al, 1984; Dugard and Scott, 1984).

The pentyl acetate isomer is absorbed through human epidermis at a faster rate than 2- methylbutyl acetate isomer.