Cetrimonium bromide

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: Read-across to cetrimonium bromide from data on dodecyltrimethylammonium bromide. Read-across justifications are provided in the endpoint summary.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1979

Materials and methods

Principles of method if other than guideline:

Percutaneous absorption of 14C-labelled test substance in rats

GLP compliance:

no

Remarks:

Study performed before GLP Guideline

Test material

Test material information

Constituent 1

Reference substance name:

Dodecyltrimethylammonium bromide

EC Number:

214-290-3

EC Name:

Dodecyltrimethylammonium bromide

Cas Number:

1119-94-4

Molecular formula:

C15H34N.Br

IUPAC Name:

N,N,N-trimethyldodecan-1-aminium bromide

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): [14C] Dodecyltrimethylammonium bromide (DTB)
- Specific activity (if radiolabelling): 7.6 mCi/mmol; 24.7 µCi/mg
- Locations of the label (if radiolabelling): [1-14C] dodecyl
- Obtained from Farbwerke Hoechst AG, Frankfurt, Germany.

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200-230 g
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): free access to food
- Water (e.g. ad libitum): free access to water

Administration / exposure

Type of coverage:

other: glass cap with holes to avoid occlusive conditions

Vehicle:

other: two tests with aqueous solution (rinse off and leave on), one with hair-rinse preparation

Duration of exposure:

Test with rinse off: 15 minutes
Test with hair-rinse preparation: 5 minutes
Test with leave on: 48 hours

Doses:

Rinse off:
- Nominal doses: 200 µl, 1% solution, 10 cm2
- Actual dose: 1.92 mg
- Actual doses calculated as follows: 0.19 mg/cm2
Hair-rinse preparation:
- Nominal doses: 261-293 mg, 0.5% solution, 8 cm2
- Actual dose: 1.1-1.2 mg
- Actual doses calculated as follows: 0.14-0.15 mg/cm2
Leave on:
- Nominal doses: 240 µl, 3% solution, 8 cm2
- Actual dose: 7.35 mg
- Actual doses calculated as follows: 0.92 mg/cm2

No. of animals per group:

Test with rinse off - aqueous and hair-rinsing preparation: 5 animals per group
Test with leave on: 3 animals

Control animals:

no

Details on study design:

Dorsal hair was clipped one day before application. The animals were anaesthetized before treatment. Treatment was applied to the marked test area of clipped skin, lathered for 3 min with a glass rod. After treatment, the test area was covered by a glass cap fitted with holes to avoid occlusive conditions and was glued to the skin avoiding contamination of the treated area with the adhesive.

Test with rinse off: Treatment of 200 µl 1% aqueous solution was applied a 10 cm2 test area and left for 15 minutes before rinsing with 100 ml water. Animals were held for 72 hours in individual metabolism cages, urine and faeces collected separately and removed every 24 hours. Radioactivity was determined in the urine, faeces and rinsings, the kidneys and liver, skin removed from the application site, the homogenized carcass, absorbant tissue and glass cap.

Test with hair-rinse preparation with rinse off: Treatment of 261-293 mg 0.42% hair-rinse preparation was applied a 10 cm2 test area and left for 5 minutes before rinsing with 100 ml water. Animals were held for 48 hours in individual metabolism cages, urine and faeces collected separately and removed every 24 hours. Blood samples were taken from the tail vein after 0.5, 1, 3, 5, 22, 26, 30, 46, and 50 hours after application. Radioactivity was determined in the urine, faeces, rinsings, blood samples, the homogenized carcass, absorbant tissue and glass cap.

Test with leave on: Treatment of 240 µl 3% aqueous solution was applied a 8 cm2 test area and left for 48 hours. Animals were held for 48 hours in individual metabolism cages, urine and faeces collected separately and removed every 24 hours. Blood samples were taken from two rats via a jugular cannula during the periods 0-7.5, 22-30 and 46-50 hours after application at time intervals of 30 or 60 min. Radioactivity was determined in the urine, faeces , blood samples, removed treated skin, the homogenized carcass and glass cap.

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

Rinse off:
- Urine: 0.32±0.115%
- Faeces: 0.18±0.08%
- Carcass & tissues: 0.09±0.06%
- Liver: 0.004±0.001%
- Kidneys: 0.001±0.0003%
- Rinsings: 81.4±1.77%
- Application site: 13.2±2.96%
Hair-rinse preparation:
- Urine: 0.019±0.013%
- Faeces: 0.013±0.017%
- Carcass & tissues: 0.061±0.47%
- Rinsings: 80.4±3.41%
- Application site: 4.11±2.21%
Leave on:
- Urine: 1.76±1.21%
- Faeces: 0.28±0.22%
- Carcass & tissues: 1.11±0.75%
- Application site: 93.2±5.76%

Total recovery:

Rinse-off: 95.3±2.41%
Hair-rinse preparation with rinse off: 92.6±3.13%
Leave on: 96.4±7.09%

Percutaneous absorption

Percutaneous absorption 1

Dose:

0.19 mg/cm2

Parameter:

percentage

Absorption:

0.59 %

Remarks on result:

other: 72 hours

Remarks:

Aqueous solution with rinse-off

Percutaneous absorption 2

Dose:

0.14-0.15 mg/cm2

Parameter:

percentage

Absorption:

0.093 %

Remarks on result:

other: 48 hours

Remarks:

Hair-rinse preparation with rinse-off

Percutaneous absorption 3

Dose:

0.92 mg/cm2

Parameter:

percentage

Absorption:

3.15 %

Remarks on result:

other: 48 hours

Remarks:

Leave-on aqueous solution

Any other information on results incl. tables

Percutaneous absorption of the surfactant was very low. Of the radioactivity applied, 13.2% remained on the skin after rinsing, a total of 0.59% of the applied radioactivity was absorbed and within the first 24 hours 0.35% was excreted with the urine.

When applied in hair rinsing preparation under conditions of normal use the percutaneous absorption was decreased and only 0.016% of the applied radioactivity was excreted in the first 24 hours and 4.11% remained on the application site. No significant radioactivity was detected in the blood.

When left on the percutaneous absorption was 3.15 % of the radioactivity applied. In the experiments with rinsing, the excretion was lower on day 2, but when left on there was a marked increase in absorption on day 2. The authors suggested that this was caused by a slight but invisible damage to the skin. In two of the rats, the blood level of surfactant was below detection limit (10 ppb) for the first 5 hours. Significantly higher level was detected in rat 3 (less than 100 ppb unchanged dodecyltrimethylammonium bromide).

Applicant's summary and conclusion

Conclusions:

Percutaneous absorption of the surfactant was very low. When applied in aqueous solution and rinse off after 15 min, the percutaneous absorption was 0.59% for a dose of 0.19 mg/cm2 and 0.093% when applied in hair-rinse preparation at a dose of 0.14-0.15 mg/cm2 and rinsed off after 5 min. Without rinse off, the absorption was 3.15% when applied in aqueous solution at a dose of 0.92 mg/cm2.

This study and the absorption rate of 3.15% for dodecyl trimethyl ammonium bromide was used by the SCCS for systemic bioavailability and risk assessment of alkyl (C16,C18;C22) trimethylammonium chlorides (SCCS/1246/09)

Executive summary:

The reported study examines the percutaneous adsorption of radiolabelled dodecyltrimethylammonium bromide through non-occluded rat skin.

Percutaneous absorption of the surfactant was very low. When applied in aqueous solution and rinse off after 15 min, the percutaneous absorption was 0.59% for a dose of 0.19 mg/cm2 and 0.093% when applied in hair-rinse preparation at a dose of 0.14-0.15 mg/cm2 and rinsed off after 5 min. Without rinse off, the absorption was 3.15% when applied in aqueous solution at a dose of 0.92 mg/cm2.