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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973-01-15 to 1975-08-08
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Methods and results were adequately documented and scientifically defensible. Pre-GLP
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Objective of study:
absorption
excretion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
N/A
GLP compliance:
no
Remarks:
Pre-GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): dodecyl dimethyl amine oxide (DDAO)
- Molecular formula (if other than submission substance): N/A
- Molecular weight (if other than submission substance): 235.7
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): N/A
- Substance type: active
- Physical state: no data
- Radiochemical purity (if radiolabelling): >98.5%
- Specific activity (if radiolabelling): 100 uCi 14C
- Locations of the label (if radiolabelling): 1-14C-dodecyl
- Expiration date of radiochemical substance (if radiolabelling): N/A
Radiolabelling:
yes

Test animals

Species:
human
Strain:
other: N/A
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: N/A
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: 12 hours
- Housing: t he subjects employed were volunteers who remained at the test facility throughout the course of the study
- Individual metabolism cages: N/A
- Diet (e.g. ad libitum): N/A
- Water (e.g. ad libitum): N/A
- Acclimation period: N/A
- Other: two human subjects participated in this study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): N/A
- Humidity (%):N/A
- Air changes (per hr): N/A
- Photoperiod (hrs dark / hrs light): N/A

IN-LIFE DATES: From: N/A To: N/A

Administration / exposure

Route of administration:
dermal
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:N/A


DIET PREPARATION
- Rate of preparation of diet (frequency): N/A
- Mixing appropriate amounts with (Type of food): N/A
- Storage temperature of food: N/A

VEHICLE
- Justification for use and choice of vehicle (if other than water): N/A
- Concentration in vehicle: N/A
- Amount of vehicle (if gavage): N/A
- Lot/batch no. (if required): N/A
- Purity: N/A

HOMOGENEITY AND STABILITY OF TEST MATERIAL: N/A
Duration and frequency of treatment / exposure:
- Single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
- The dose was 10 mg (100 µCi 14C) per subject
No. of animals per sex per dose:
- Two human subjects
Control animals:
no
Positive control:
N/A
Details on study design:
- Dose selection rationale: N/A
- Rationale for animal assignment (if not random): N/A
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Distribution)
- Tissues and body fluids sampled: blood
- Time and frequency of sampling: N/A
- Other: hN/A

PHARMACOKINETIC STUDY (Excretion)
- Tissues and body fluids sampled: urine, feces and carbon dioxide
- Time and frequency of sampling: urine was collected at 0-6, 6-24, 24-48, 48-72 and 72-144 hours; carbon dioxide was collected at 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours (no data is presented regarding the sampling time of feces)
- Other: N/A

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: N/A
- Time and frequency of sampling: N/A
- From how many animals: (samples pooled or not): N/A
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC): N/A
- Limits of detection and quantification: N/A
- Other: N/A

TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable): N/A
Statistics:
N/A

Results and discussion

Preliminary studies:
N/A

Toxicokinetic / pharmacokinetic studies

Details on absorption:
A small percentage of cutaneously applied [1-14C-dodecyl]-test substance was absorbed by humans as indicated by the appearance of 0.01 and 0.23% of the administered radioactivity in the excretion products of the two human subjects. The percent absorption in the two human subjects was determined to be < 0.2% based on assumption of maximum non-detectable amounts in all urine collections falling in the non-detectable range. More than 92% of the applied dose could be recovered from the site by swabbing with moist gauze eight hours after dose application. The tape strippings of the application site showed that the stratum corneum contained less than two-tenths of one percent of the applied dose.

All blood samples taken contained less than 3.0E-5 percent of the dose per gram
Details on distribution in tissues:
N/A
Details on excretion:
A small percentage of cutaneously applied [1-14C-dodecyl]-test substance was absorbed by humans as indicated by the appearance of 0.01% and 0.23% of the administered radioactivity in the excretion products of the two human subjects.
Toxicokinetic parameters
Toxicokinetic parameters:
other: no parameters identified

Metabolite characterisation studies

Metabolites identified:
not specified
Details on metabolites:
N/A

Any other information on results incl. tables

N/A

Applicant's summary and conclusion

Conclusions:
Only a small percentage of cutaneously applied [1-14C-dodecyl]-test substance was absorbed by humans as indicated by the appearance of 0.01 and 0.23% of the administered radioactivity in the excretion products of the two human subjects.  The percent absorption in the two human subjects was determined to be 0.2% based on assumption of maximum non-detectable amounts in all urine collections falling in the non-detectable range.  More than 92% of the applied dose could be recovered from the site by swabbing with moist gauze eight hours after dose application.  The tape strippings of the application site showed that the stratum corneum contained less than two-tenths of one percent of the applied dose. 
Executive summary:

The absorption and excretion pattern of [1-14C-dodecyl]-C10-16 alkyl dimethyl amine oxide administered dermally to two human subjects was examined.  The subjects employed were volunteers who remained at the test facility throughout the course of the study.  Each subject was given a complete physical examination before and after the study.  The physical examination included clinical chemistries, ophthalmoscopic eye examination, EKG, hematology and blood pressure.  Recommended procedures for informed consent and experimental review were followed.  Before dosing, subjects were food fasted for twelve hours.  Zero time blood samples were taken immediately before dosing .

An area 15 cm x 4 cm was marked off on the outer surface of the subjects’ forearms which had been clipped free of hair and inspected for breaks.  One-half mL of an aqueous solution containing 10 mg of [1-14C-dodecyl]-C10-16 alkyl dimethyl amine oxide (100 µCi14C) was applied evenly over the site with a plastic syringe.  The site was allowed to dry by evaporation and was covered with a non-occlusive, plastic shield.  After eight hours, the C10-16 alkyl dimethyl amine oxide remaining at the application site was removed by repeatedly (10 x) swabbing the skin with water moistened gauze pads.  The portion of the radioactive dose retained in the stratum corneum was assayed by repeatedly (10 x) stripping a 7.2 squared centimeter area within the area of application with tape.  Normal handling and exposure of the application site was permitted after these procedures.  Urine was collected in polyethylene bottles over the intervals 0-6 hours and 6-24 hours, and subsequently over 24-hour intervals through 144 hours.  During the collection period, samples were stored at 0° C; upon completion of a collection interval, the urine samples were frozen on dry ice.  Feces samples were collected individually as available in plastic bags and were stored frozen.  Expired CO2was collected in a modified Hanks apparatus.  The air flow rate through the collection box was 12 L/min.  Carbon dioxide collections on the orally dosed subjects were performed at 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours after dosing.  The collection period was 15 minutes.  Total expired radioactivity was computed from these samples of expired gases.

A small percentage of cutaneously applied [1-14C-dodecyl]-C10-16 alkyl dimethyl amine oxide was absorbed by humans as indicated by the appearance of 0.01 and 0.23% of the administered radioactivity in the excretion products of the two human subjects.  The percent absorption in the two human subjects was determined to be 0.2% based on assumption of maximum non-detectable amounts in all urine collections falling in the non-detectable range.  More than 92% of the applied dose could be recovered from the site by swabbing with moist gauze eight hours after dose application.  The tape strippings of the application site showed that the stratum corneum contained less than two-tenths of one percent of the applied dose.