2,4-dinitroanisole

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 December 2011 - 31 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dinitroanisole

EC Number:

204-310-9

EC Name:

2,4-dinitroanisole

Cas Number:

119-27-7

Molecular formula:

C7H6N2O5

IUPAC Name:

2,4-dinitroanisole

Test animals

Species:

other: human

Details on test animals or test system and environmental conditions:

N/A

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Duration of exposure:

8 hours

Doses:

- Actual doses: 100 mg

No. of animals per group:

1

Control animals:

no

Details on study design:

TEST SITE
- Coverage: 0.64 cm2

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: abdominal human skin (from autopsy or surgery)
- Ethical approval if human skin: not specified
- Preparative technique:
Full thickness abdominal human skin (from autopsy or surgery) was obtained from the National Disease Research Interchange (NDRI), Philadelphia, Pennsylvania. The whole skin was stored frozen at -85 °C. Before starting the experiments, the skin was placed in a Petri dish containing a buffer solution at room temperature. The subcutaneous fat was removed with blunt forceps, and the skin was cleaned with a buffer solution and placed on a dissecting board. Circular pieces of skin sections (0.64 cm2) were prepared from the skin with the help of a metallic Arch Punch (18 mm; Osborne and Company). The epidermis was teased from dermis as described by Frasch et al. 2011. The skin discs were wrapped in Saran® Wrap and submerged in a 60°C buffer for approximately 70 seconds. The skin was unwrapped and placed in a Petri dish containing a buffered solution. The dermis of the skin discs was teased from the epidermis carefully using blunt forceps or cotton swabs under a binocular microscope. Care was taken not to damage the skin. During epidermal membrane separation, a thin layer of stratum corneum was easily separated from the skin. The epidermal membranes remaining were used for testing. The epidermal membranes were evaluated under a dissection microscope to ensure that they were free of any damage. The epidermal membranes (without stratum corneum) were placed on wax paper moistened with a buffered solution and frozen (-30°C) prior to experimental use.

Results and discussion

Percutaneous absorption

Key result

Time point:

8 h

Dose:

100 mg

Parameter:

rate

Absorption:

ca. 0.002 %

Applicant's summary and conclusion

Conclusions:

The analysis of the absorbed chemical in the receptor fluid data showed that steady state fluxes to an infinite dose (100 milligrams (mg)) of neat DNAN was 1.1 μg/cm2 /hr.

The cumulative dermal absorption of DNAN over 8 hours was 12.5 μg/cm2