TDI Biuret

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

No guidelines exist for this kind of study. The study was performed considering parts of the OECD guideline No. 427, Percutaneous Absorption: in vivo method, 2004.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

m-tolylidene diisocyanate

EC Number:

247-722-4

EC Name:

m-tolylidene diisocyanate

Cas Number:

26471-62-5

IUPAC Name:

2,4-diisocyanato-1-methylbenzene

Details on test material:

2,4-TDI
- Name of test material (as cited in study report): 2,4-TDI
- Supplier: Sigma-Aldrich
- Analytical purity: 99.7%
- Batch No.: 6124X
- Stability under test conditions: stability was guaranteed under the storage conditions until 04 May 2009
- Homogeneity: homogeneous by visual inspection and due to the high purity

2,6-TDI
- Name of test material (as cited in study report): 2,6-TDI
- Supplier: Sigma-Aldrich
- Analytical purity: 99.8%
- Batch No.: 1284332
- Stability under test conditions: stability was guaranteed under the storage conditions until 31 Aug 2007
- Homogeneity: homogeneous by visual inspection and due to the high purity

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Chales River Laboratories, Sulzfeld, Germany
- Age at study initiation: 10 - 12 weeks
- Weight at study initiation: ca. 300 g
- Fasting period before study: no
- Housing: Macrolon cages type III
- Individual metabolism cages: no
- Diet: Provimi Kliba SA, Kaiseraugust, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Photoperiod: natural day/night rhythm with additional artificial light as required during working hours

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

1 min (skin sample), 1 h, 2 h, 4 h, 8 h

Doses:

300 µl/kg which corresponds to 360 mg/kg

No. of animals per group:

2 animals per exposure period (1 h, 2 h, 4 h, 8 h);
1 animal was sacrificed without exposur (untreated control)
1 animal for skin preparation (2 skin samples were prepared) and 1 min exposure of the preparated skin
= 10 animals in total

Control animals:

yes

Remarks:

Negative control: untreated skin sites (2) of one animal; Positive control: 10 µl of the undiluted mixture of 2,6-TDI and 2,4-TDI (1:1, v:v) directly given into the reagent

Details on study design:

DOSE PREPARATION
undiluted 2,6-TDI and 2,4-TDI (1:1, v:v)

APPLICATION OF DOSE:
10 µl/cm2 (100µl/10 cm2)

TEST SITE
- Preparation of test site: clipping and cleaning with acetone at least 24 h before treatment
- Area of exposure: 10 cm2, difined by a rubber ring and spacer
- Type of cover / wrap used: a permeable (gauze) dressing containing a chorcoal filter and the whole was further protected by a semi-occlusive adhesive bandage

SAMPLE PREPARATION
- Preparation details: animals were sacrificed, skin samples were prepared, the skin samples were transferred into the reagent (consisting of Dibutylamine in toluene). It was guaranteed that samples remained submersed in the reagent
- Storage procedure: after reaction time of 15 min samples were stored at 4°C

ANALYSIS
The amount of free isocyanates on the skin was determined by chemical analysis

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Any other information on results incl. tables

- Analytical results of 2,6- and 2,4 -TDI on rat skin are shown in table 1. The negative control (0µl/10cm2) showed no background detection of isocyanate reactivity in untreated skin.

- Positive control (1:1 mixture of 2,6 -TDI and 2,4 -TDI) resulted in values of 40 and 100 mg/100 µl. Therefore the nominal ratio of 1:1 varied from the experimental ratio of 4:10 (due to preparation of stock solution or calibration of analytical equipment)

Table 1: Analytical results of 2,6 -TDI and 2,4 -TDI on rat skin after different exposure periods

Nominal dose [µl/10 cm2]	Positive control	0	0	100	100	100	100	100	100	100	100	100	100
Exposure time [min]	-	-	-	1	1	60	60	120	120	240	240	480	480
Animal no.	-	1	1	2	2	3	4	5	6	7	8	9	10
2,6-TDI [mg/sample]	40	<1	<1	12	12	18	8	8	10	6	4	2	3
2,4-TDI [mg/sample]	100	<1	<1	57	59	56	24	24	29	21	14	14	18