Quaternary ammonium compounds, C18-22 (even numbered) alkyltrimethyl, chlorides; Docosyltrimethylammonium chloride; C18-22 TMAC

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Data source

Reference

Reference Type:

publication

Title:

Percutaneous absorption of dodecyltrimethylammonium bromide, a cationic surfactant, in the rat

Author:

Bartnik FG and Wingen F

Year:

1979

Bibliographic source:

Food Cosmet Toxicol. 1979 Dec;17(6):633-7

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The percutaneous absorption of the test substance was determined by performing in vivo cutaneous application study in rats. The 240 µL sample of a 3% solution [14C] test substance water was applied to the intact clipped skin of male Wistar rats under occlusive conditions. The samples of urine, faeces, rinsing, blood, removed treated skin, homogenized carcass and glass cap (occlusive dressing) were collected. The Radioactivity was determined (% of 14C administered dose) for samples to calculate the percutaneous absorption of test substance.

GLP compliance:

no

Remarks:

Study from Pre-GLP period

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, C18-22 (even numbered) alkyltrimethyl, chlorides

Molecular formula:

Molecular formula of the major constituents: C21H46NCl (C18 carbon chain) C23H50NCl (C20 carbon chain) C25H54N1Cl (C22 carbon chain)

IUPAC Name:

Quaternary ammonium compounds, C18-22 (even numbered) alkyltrimethyl, chlorides

Test material form:

solid

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Male Wistar rats (200-230 g)

Administration / exposure

Type of coverage:

other: Light glass cap (fitted with small holes to avoid occlusive conditions and was glued to the skin with a special adhesive, care being taken to avoid contamination of the treated area with the adhesive)

Vehicle:

water

Duration of exposure:

5 and 15 minutes, 48 h

Doses:

0.5% 1% and 3% test substance in water

No. of animals per group:

1 group of 3 animals

Control animals:

no

Details on study design:

- Preparation of test site: Shaven skin
- Concentration of test substance: 3% concentration of [14C]-N-dodecyltrimethylammonium bromide
- Specific activity of test substance: Not indicated
- Volume applied: 240µL
- Size of test site: 8 cm² or other
- Exposure period: 2 days
- Sampling time: Blood: 0.5, 1, 5, 22, 26, 30, 46, 50; Urine & faeces: 24 and 48 h
- Samples: Blood, urine, faeces, carcass, skin with substance not removable

Results and discussion

Signs and symptoms of toxicity:

not examined

Remarks:

Not indicated – unlikely with low TMAC dose applied

Dermal irritation:

not examined

Total recovery:

96.4 ± 7.09%

Percutaneous absorption

Percutaneous absorption 1

Key result

Time point:

72 h

Dose:

1%

Parameter:

percentage

Remarks:

0.59%

Remarks on result:

other: study with radiolabelled test substance with rinsing

Percutaneous absorption 2

Key result

Time point:

48 h

Dose:

0.5%

Parameter:

percentage

Remarks:

0.093%

Remarks on result:

other: study with radiolabelled hair rinse formulation of the test substance

Percutaneous absorption 3

Key result

Time point:

48 h

Dose:

3%

Parameter:

percentage

Remarks:

3.15%

Remarks on result:

other: study with radiolabelled test substance without rinsing

Any other information on results incl. tables

Cutaneous application of [14C] test substance with rinsing

Application of 1% aqueous solution of [14C] test substance on the skin wih rinsing resulted in a very low percutaneous absorption of the surfactant. The total absorption was 0.59% of the applied radioactivity. Most of the amount absorbed was excreted in the urine. Within the first 24 h, 0.35% of the applied surfactant was excreted. Of the radioactivity applied, 13.2% remained on the skin after rinsing, demonstrating the relatively high affinity of the surfactant for skin.

Cutaneous application of [14C] test substance in a hair-rinse preparation

Application of [14C] test substance in a hair-rinse preparation (0.5% test substance) under conditions of normal use resulted in a marked decrease in the percutaneous absorption of the surfactant.The total absorption was 0.093% of the applied radioactivity. Only 0.016% of the amount applied was excreted in the first 24 h and 4.11% of the surfactant remained at the application site. No significant radioactivity was detected in the blood of the treated animals during the experiment (detection limit 10 ng surfactant/g blood).

Cutaneous application of [14C] test substance without rinsing

Application of a 3% solution of [14C] test substance on theskin without any rinsing resulted in percutaneous resorption of 3.15% of the applied radioactivity.In the experiments involving rinsing, the excretionof radioactivity wasalways lower on Day 2 than on Day 1, but in this experiment there was a marked increase in absorption on Day 2. The possibility cannot be excluded that the relatively long contact of the skin with the surfactant caused a slight but invisible damage to the skin, resulting in higher absorption rates. In two of the rats, the blood level of the surfactant was below the detection limit of 10 ppb (10 ng/g) for the first 5 h of cutaneous application of test substance.

Applicant's summary and conclusion

Conclusions:

Under study conditions, percutaneous absorption of the [14C] test substance was found to be 0.6% with rinsing and 3.15% without rinsing.

Executive summary:

A study was conducted to determine the percutaneous absorption of the radiolabelled read across substance, [C14] C12 TMAB, under occlusive conditions on rat skin. The test substance was applied to the intact clipped skin of 3 rats under three scenarios: at 1% and 3% in aqueous solution followed by subsequent with and without rinsing respectively and 0.5% hair-rinse formulation of test substance. Application in a cream hair-rinse preparation under user conditions resulted in the absorption of about 0.1% of the administered radioactivity after 48 h. No measurable radioactivity was present in the blood. However, application of the test substance at 1% and 3% aqueous without subsequent rinsing solution gave a somewhat higher absorption (0.6% after 72 h and 3.15% after 48 h respectively), whereas, some radioactivity was found in the blood after application of the test substance to the skin without subsequent rinsing. Overall the percutaneous absorption of the test substance was low. Under study conditions, percutaneous absorption of the radiolabelled test substance was found to be 0.6% with rinsing and 3.15% without rinsing (Bartnik 1979).