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Toxicological information

Dermal absorption

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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:
other: Guideline study (OECD 428)

Data source

Reference
Reference Type:
review article or handbook
Title:
European Union Risk Assessment Report TRIS(2-CHLORO-1-METHYLETHYL) PHOSPHATE (TCPP)
Author:
European Commission Joint Research Centre
Year:
2008
Bibliographic source:
In: RISK ASSESSMENT of May 2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14C-lableded

Test animals

Species:
human
Strain:
not specified
Sex:
not specified

Administration / exposure

Type of coverage:
not specified
Vehicle:
not specified
Duration of exposure:
8 hours
Doses:
0.002, 0.1 and 1.0 mg/cm2
Control animals:
no
Details on study design:
DOSE PREPARATION
- The dose solutions were prepared on the day of application. [14C]-TCPP was mixed with nonradiolabelled TCPP to obtain a target amount of radioactivity of ca. 1 x 106 dpm per skin membrane. For the lowest concentration, ca. 0.5 x 106 dpm per membrane was the maximum amount of radioactivity possible.

VEHICLE
- In order to ensure equal distribution over the skin surface, the relevant dose of TCPP was applied in a small volume of acetone (20µl) which was evaporated directly after application using a warmed air-flow.

REMOVAL OF TEST SUBSTANCE
- At 8 hours post dose, unabsorbed TCPP was removed from the skin using 3% Teepol solution
in water and cotton swabs.
- The diffusion cell was dismantled at 24 hours post dose and the receptor and donor compartments were washed twice with 1.0 ml ethanol, each skin membrane was tape stripped 10 times and the remaining skin was solubilised.

SAMPLE COLLECTION
- Receptor fluid samples were collected from 0-1 h and 1-2 h, followed by 2-hour intervals until 24 hours after application.

ANALYSIS
- All samples were analysed using liquid scintillation counting.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Total recovery:
The mean recovery of TCPP in human skin was 99.7 ± 6.2%, 99.2 ± 5.7% and 93.5 ± 6.9%, for the high, mid and low doses, respectively.
Percutaneous absorptionopen allclose all
Dose:
2.049 µg/cm2
Parameter:
percentage
Absorption:
ca. 22.7 %
Remarks on result:
other: 8 h
Dose:
99.96 µg/cm2
Parameter:
percentage
Absorption:
ca. 13.6 %
Remarks on result:
other: 8 h
Dose:
997.33 µg/cm2
Parameter:
percentage
Absorption:
ca. 3.7 %
Remarks on result:
other: 8 h

Any other information on results incl. tables

The mean penetration of TCPP into the receptor fluid after 24 hours was 0.39, 9.64 and 17.75 µg/cm2, for the low, mid and high dose, respectively. The mean maximal flux was 0.027, 0.602 and 0.836 µg/cm2/h, for the three doses respectively. The mean total absorption is defined as the compound related radioactivity present in the receptor fluid, the receptor compartment wash and the skin membranes (excluding tape strips). At 0.002 mg/cm2, the total absorption ranged from 17 % to 32.8%, with a mean total absorption of 22.7 %. At the mid dose of 0.1 mg/cm2, the total absorption ranged from 9.8% to 18.2%, with the mean total absorption of 13.6%. At 1 mg/cm2, the total absorption ranged from 2.3% to 5.2%, with a mean total absorption of 3.7%.

Applicant's summary and conclusion

Conclusions:
In in vitro dermal absorption studies, the amount of penetrated substances found in the receptor fluid are considered to be systemically available. The epidermis (except for the stratum corneum) and the dermis are considered as a sink, and therefore amounts found in these tissues should also be considered absorbed. Therefore, a worst case mean total absorption value of 23 % should be taken for scenarios where there is potential exposure to “neat” TCPP. This is considered to be a reasonable worst case value since 16 of 18 individual membrane measurements taken were found to be 23% or lower.