(carboxymethyl)dimethyl-3-[(1-oxotetradecyl)amino]propylammonium hydroxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

18 Jan - 11 Feb 1984

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

positive control missing, substance purity not given

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted in 1992

Deviations:

yes

Remarks:

no reliablity check was performed

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was conducted prior to the current requirement in Regulation (EC) 1907/2006 to perform an LLNA study (OECD 429) as the preferred in vivo skin sensitisation study.

Test material

Test material information

Constituent 1

Reference substance name:

(carboxymethyl)dimethyl-3-[(1-oxotetradecyl)amino]propylammonium hydroxide

EC Number:

261-684-6

EC Name:

(carboxymethyl)dimethyl-3-[(1-oxotetradecyl)amino]propylammonium hydroxide

Cas Number:

59272-84-3

Molecular formula:

C21H42N2O3

IUPAC Name:

(carboxymethyl)dimethyl-3-[(1-oxotetradecyl)amino]propylammonium hydroxide

Test material form:

solid

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Remarks:

albino

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands
- Weight at study initiation: males: 237 - 315 g; females: 235 - 295 g
- Housing: individual in suspended stainless steel cages, fitted with wire mesh floors and fronts
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 1
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

propylene glycol

Concentration / amount:

20%

Day(s)/duration:

1

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

10%

Day(s)/duration:

48 hours

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Challenge

Route:

epicutaneous, semiocclusive

Vehicle:

other: vaseline

Concentration / amount:

5% or 1%

Day(s)/duration:

24 hours

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

20 animals (10 male and 10 female) for test group and 10 animals (5 male and 5 female) for control group

Details on study design:

RANGE FINDING TESTS: no data available

MAIN STUDY
A. INDUCTION EXPOSURE
Induction is effected in a two-stage operation consisting of, firstly, three pairs of intradermal injections made simultaneously and, secondly, one week later, a closed patch exposure performed over the injection sites. For this purpose an area of c. 24 cm² of dorsal skin in the shoulder region is clipped free of hair with electric clippers.

Intradermal injections:
Three pairs of intradermal injections are made in the clipped area.
The preparations injected into the skin of the test animals are the following:
- sites a(left) and a(right): Freund’s Complete Adjuvant (FCA)
- sites b(left) and b(right): a dilution of the test substance in a suitable carrier (propylene glycol)
- sites c(left) and c(right): a dilution of the test substance in a mixture of FCA and carrier (1:1).
The preparations injected into the skin of the control animals are the following:
- sites a(left) and a(right): FCA
- sites b(left) and b(right): carrier
- sites c(left) and c(right): a mixture of FCA and carrier (1:1).

Skin readings are made 24 h after the treatment.

Topical application:
One week after induction by the intradermal injections the same area of the skin of the animals is closely shaved again. The test animals are treated as follows:
A 2 x 4 cm patch of Whatman No 3 MM filter paper is loaded with the appropriate mixture of the test substance and carrier. The patch is placed over the sites of the intradermal injections and covered with a piece of PVC foil and a piece of Leukopor hypo-allergic paper bandage. This, in turn, is secured with a 7.5 cm wide Tensoplast bandage. The dressing is left in place for 48 h. The control animals are similarly treated with patches with carrier (vaseline) only.
Skin readings are made after removal of the patches.


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after topical induction
- Exposure period: 24 hours
- Test groups: test substance
- Control group: test substance
- Site: left flank
- Concentrations: 5 or 1%
- Evaluation (hr after challenge): 24 and 48 hours

Positive control substance(s):

not specified

Results and discussion

Positive control results:

no data available

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5% at challenge

No. with + reactions:

1

Total no. in group:

9

Clinical observations:

1 male with score 1 for erythema and edema, respectively

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5% at challenge

No. with + reactions:

0

Total no. in group:

9

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

20% intradermal induction, 10% topical induction, 5% at challenge

No. with + reactions:

2

Total no. in group:

20

Clinical observations:

1 male with edema score of 1 and one male with erythema and edema score 1

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

20% intradermal induction, 10% topical induction, 5% at challenge

No. with + reactions:

0

Total no. in group:

20

Results 5

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

One control female died on Day 9 of the study because of a prolapse of the rectum. All other animals remained in good health during the experimental period.

The challenge treatment with a 1% dilution - a concentration which is one fifth of the non-irritant concentration - did not elicit any sensitisation reaction under the conditions of the test.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification