Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study according to scientific practice using radiolabelled material
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 427 (Skin Absorption: In Vivo Method)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Hostapur SAS - 14C
- Physical state: solid
- Analytical purity: 100 %
- Impurities (identity and concentrations): no
- Composition of test material, percentage of components: 100 %
- Isomers composition: n.a.
- Purity test date: 1976-01-16
- Lot/batch No.: 5110 I
- Expiration date of the lot/batch: 1979-12-31
- Radiochemical purity (if radiolabelling): 100 %
- Specific activity (if radiolabelling): 4.15 mCi/g
- Locations of the label (if radiolabelling): uniform (every carbon) U-C14 radiolabelled
- Expiration date of radiochemical substance (if radiolabelling): 1977-12-31
- Stability under test conditions: stable
- Storage condition of test material: refrigerator, darkness
- Other:
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ivanovas (Kißlegg, Allgäu, Germany)
- Weight at study initiation: 180 - 240 g
- Fasting period before study: 12 hours befor administration, 4 hours after administration
- Housing: individually
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): see above
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
- Humidity (%): 50 - 60 %
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Duration of exposure:
1.25 hours
Doses:
0.25 mg per animal
No. of animals per group:
6 male animals, 1 group
Control animals:
yes
Remarks:
untreated animals, same animals befor administration
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: aqueous solution
- Method of storage: refrigerator


APPLICATION OF DOSE: 0.3 mL solution ( 0.25 mg Hostapur SAS - 14C


TEST SITE
- Preparation of test site: shaved, intact back skin
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100
- Type of cover / wrap if used: occlusive


SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: no


REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: yes
- Washing procedures and type of cleansing agent: no rinsing
- Time after start of exposure: n.a.


SAMPLE COLLECTION
- Collection of blood: yes
- Collection of urine and faeces: yes
- Collection of expired air: yes
- Terminal procedure: 4 hours up to 7 days
- Analysis of organs: yes


SAMPLE PREPARATION
- Storage procedure:
- Preparation details:


ANALYSIS
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC)
- Liquid scintillation counting results (cpm) converted to dpm as follows:
- Validation of analytical procedure:
- Limits of detection and quantification:


OTHER:

Results and discussion

Signs and symptoms of toxicity:
no effects
Dermal irritation:
no effects
Absorption in different matrices:
- Occlusive cover, no enclosure rinse: yes
- Skin wash: yes
- Skin test site: yes
- Skin, untreated site: no
- Blood: yes
- Carcass: yes
- Urine: yes
- Cage wash + cage wipe: yes
- Faeces: yes
- Expired air (if applicable): yes
- Serial non-detects in excreta at termination: no
- Receptor fluid, receptor chamber, donor chamber (in vitro test system): no
- Skin preparation (in vitro test system): n.a.
- Stratum corneum (in vitro test system): (i.e tape strips): n.a.
Total recovery:
- Total recovery: 99.9 +/- 6.4 %
- Recovery of applied dose acceptable: yes
- Results adjusted for incomplete recovery of the applied dose: no
- Limit of detection (LOD): no data
- Quantification of values below LOD or LOQ: no

Applicant's summary and conclusion

Conclusions:
Sec-alkane sulfonate-sodium salts SAS exhibits low skin penetration potential. Residuals of less than 1 ppm of the administered dose were found in organs and tissues 7 days p.a.
Executive summary:

Dermal application of about 0.25 mg sec-alkane sulfonate-sodium salt SAS - 14C onto approximately 6 cm2 shaved back skin for 1,25 hours revealed maxima in blood levels about 2 to 6 hours p.a. Elimination half-life was in average about 41 hours (air approximately 15 %, urine approximately 18 %, faeces approximately 31 %). Most radioactivity was found in the bandage (approximazely 35 %) whereas only about 2.2 % was detected in the treated skin 7 days p.a. The available data point to a low skin penetration potential of sec-alkane sulfonate-sodium salts SAS.