2,2'-[[5-acetamido-4-[(2-bromo-4,6-dinitrophenyl)azo]-2-methoxyphenyl]imino]diethyl diacetate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

read-across

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Principles of method if other than guideline:

The cutaneous penetration kinetics of Disperse Blue 79:1 in human abdominal skin samples were measured using in vitro techniques for a 6 h period along with parallel testing of other subtances. The amount of test substance penetrating skin samples and collected in the effluent were measured by liquid scintillation spectrometry or high-performance liquid chromatography (HPLC).

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-[[5-acetamido-4-[(2-bromo-4,6-dinitrophenyl)azo]-2-methoxyphenyl]imino]diethyl diacetate

EC Number:

222-813-1

EC Name:

2,2'-[[5-acetamido-4-[(2-bromo-4,6-dinitrophenyl)azo]-2-methoxyphenyl]imino]diethyl diacetate

Cas Number:

3618-72-2

Molecular formula:

C23H25BrN6O10

IUPAC Name:

2-{[2-(acetyloxy)ethyl]({4-[ (E)-2-(2-bromo-4,6-dinitrophenyl)diazen-1-yl]-5acetamido-2-methoxyphenyl})amino}ethyl acetate

Details on test material:

Disperse Blue 79:1 (Br)
CAS No. 3618-72-2

Radiolabelling:

yes

Results and discussion

Total recovery:

No information available.

Any other information on results incl. tables

Skin penetration of the test substance, applied to human abdominal skin, could not be detected by HPLC above the minimum detection limit of 1 µg/mL. The results thus indicate that human dermal exposure to the test substance would probably not result in a significant absorbed dose.

Applicant's summary and conclusion

Conclusions:

Skin penetration of Disperse Blue 79:1 (Br), applied to human abdominal skin, could not be detected by HPLC above the minimum detection limit of 1 µg/mL. The results thus indicate that human dermal exposure to the test substance would probably not result in a significant absorbed dose.

Executive summary:

The cutaneous penetration kinetics of ³H-water (550 µl) or ¹⁴C-mannitol (550 µl; 1 mg/ml) through excised pig ear and human abdominal skin samples were measured using in vitro techniques for a 6-hr period. In addition, the cutaneous penetration kinetics of ¹⁴C-Disperse Blue 79:1 (Br) (110 µl; 5 mg/ml), Reactive Blue 19 (550 µl; 1 mg/ml) and Direct Blue 218 (550 µl; 1 mg/ml) were evaluated by the same in-vitro techniques using human abdominal skin samples. The CAS numbers were 2580-78-1 (Reactive Blue 19), 10401-50-0 (Direct Blue 218), 3618-72-2 (Dispersion Blue 79:1 (Br)), and 69-65-8 (D-Mannitol). Test substances penetrating skin samples and collected in the effluent were measured by liquid scintillation spectrometry or high-performance liquid chromatography (HPLC).

For pig ear skin, the lag time before skin penetration of ¹⁴C-mannitol or ³H-water reached a steady-state rate was 2.77 and 1.75 hr, respectively. The steady-state rate of penetration of mannitol or water through pig ear skin was calculated to be 0.2 µg/cm²/hr and 6.12 mg/cm²/hr, respectively, while the Kp value was calculated to be 0.21 x 10^-3cm/hr and 6.12 x 10^-3cm/hr, respectively. These results were similar to those reported by Scott and Dick (1990). For human abdominal skin, the lag time before skin penetration of ¹⁴C-mannitol or ³H-water reached a steady-state rate was 3.49 and 2.17 hr, respectively. The steady-state rate of penetration of mannitol or water through human skin was calculated to be 0.006 µg/cm²/hr and 2.43 mg/cm²/hr, respectively, while the Kp value was calculated to be 0.006 x 10^-3cm/hr and 2.43 x 10^-3cm/hr, respectively.

These results show that significantly more ³H-water can penetrate both pig ear skin and human abdominal skin than ¹⁴C-mannitol. However, the total penetration of water and mannitol after 6 hr of exposure was 2.7-times and 55-times less for human skin than for pig ear skin. Similarly, both the steady-state penetration rates and permeability constants for water and mannitol were approximately 2.5-times and 30-times less, respectively, for human skin than for pig ear skin. These results would suggest that pig ear skin is not a good animal model for human cutaneous penetration of chemicals.

For the ¹⁴C-DB-79:1 applied to human abdominal skin, the lag time before skin penetration reached a steady-state rate was 3.38 hr. The steady-state rate of penetration of DB-79:1 through human skin was calculated to be 0.0057 µg/cm²/hr. The Kp value for the skin penetration of this dye, however, could not be calculated. Skin penetration of the Reactive Blue 19 and Direct Blue 218 applied to human abdominal skin could not be detected by HPLC above the minimum detection limit of 1 µg/ml.

Little or no Disperse Blue 79:1 (Br), Reactive Blue 19 or Direct Blue 218 was detected penetrating human skin samples. These results indicate that human dermal exposure to any of these 3 dye compounds would probably not result in a significant absorbed dose.

(Sun, 1995).