Amines, N-tallow alkyltrimethylenedi-, propoxylated

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1981-05-11 to 1981-06-12

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: 2b: Comparable to guideline study with acceptable restrictions (no control group is mentioned, no positive control is included).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

1-({3-[(2-hydroxypropyl)[(9E)-octadec-9-en-1-yl]amino]propyl}amino)propan-2-ol; 1-({3-[(2-hydroxypropyl)amino]propyl}(octadecyl)amino)propan-2-ol; 1-({3-[hexadecyl(2-hydroxypropyl)amino]propyl}amino)propan-2-ol

EC Number:

614-637-2

Cas Number:

68603-75-8

Molecular formula:

R-N(CH2CHOHCH3)xCH2CH2CH2N(CH2CHOHCH3)y with x+y=3 and where R = alkyl

IUPAC Name:

1-({3-[(2-hydroxypropyl)[(9E)-octadec-9-en-1-yl]amino]propyl}amino)propan-2-ol; 1-({3-[(2-hydroxypropyl)amino]propyl}(octadecyl)amino)propan-2-ol; 1-({3-[hexadecyl(2-hydroxypropyl)amino]propyl}amino)propan-2-ol

Details on test material:

- Name of test material (as cited in study report): DINORAM SL
- Physical state: dark brown liquid
- Lot/batch No.: 2884
No other data available

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Shamrock Farms (U.K.)
- Age at study initiation: approximately 2 months
- Weight at study initiation: 322 ± 13 g (males) + 337 ± 10 g (females)
- Housing: polycarbonate cages. 2 animals/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25°C
- Humidity (%): 50 ± 20 %
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: olive oil

Induction 2

Concentration / amount:

- Induction :
* intradermal injections : test item at the concentration of 0.1% (w/w) in sterile olive oil
* topical application : test item at the concentration of 1% (w/w) in sterile olive oil

- Challenge :
topical application : test item at the concentration of 1% (w/w) in olive oil

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: olive oil

Challenge 2

Concentration / amount:

- Induction :
* intradermal injections : test item at the concentration of 0.1% (w/w) in sterile olive oil
* topical application : test item at the concentration of 1% (w/w) in sterile olive oil

- Challenge :
topical application : test item at the concentration of 1% (w/w) in olive oil

No. of animals per dose:

Treated group : 20 animals ( 10 males and 10 females)
Controls: no data

Details on study design:

RANGE FINDING TESTS:
For both the preliminary test and the main test, the application sites of all animals were:
• shaved 24 hours before any treatment

Concentrations tested in the range finding test:
By intradermal route (tested concentrations: 100 %, 10%, 5 %, 1% and 0.1% (w/w)):
• intradermal injections of the dosage form preparations (0.1 mL) were performed in the
interscapular region,
• cutaneous reactions were evaluated 24 hours after the injections.
By cutaneous route
Under the conditions of the induction phase (tested concentrations: 100%, 50%, 10%, 1% (w/w)):
• a gauze pad (approximately 4 cm2) was fully-loaded with a dosage form preparation and was
then applied to the shaved area of the skin. The gauze pad was held in place by means of an
occlusive dressing for 24 hours,
• cutaneous reactions were evaluated 1 hour after removal of the dressing.
Under the conditions of the challenge phase (tested concentrations: 100%, 50%, 10% and 1 % (w/w)):
•a gauze pad (approximately 4 cm2) was fully-loaded with a dosage form preparation and was
then applied to the shaved area of the skin. The gauze pad was held in place by means of an
occlusive dressing for 24 hours,
• cutaneous reactions were evaluated 1 hour after removal of the dressing.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal exposure and 1 epicutaneous (occlusive) exposure
- Exposure period: intradermal on day 1, epicutaneous on day 9, Sodium lauryl Sulfate 10% on day 8
- Test groups: 10 males and 10 females
- Control group: no data
- Site: the interscapular region, same site for both induction exposures
- Frequency of applications: single treatment for both intradermal and epicutaneous exposures
- Duration: intradermal exposure: single injection, epicutaneous exposure: 48h under occlusive dressing
- Concentrations:
intradermally for induction: Freund's complete adjuvant (FCA) diluted at 50% (v/v) with 0.9% NaCl, 0.1% (w/w) test item in sterile olive oil and 0.1% test item in a mixture FCA/olive oil (50/50, v/v),
epicutaneous for induction: 1% (w/w) in sterile olive oil

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Two weeks after the induction phase
- Exposure duration: 24 h under occlusive dressing
- Test groups: 10 males and 10 females
- Control group: no data
- Concentrations: 1% (w/w) in sterile olive oil
- Evaluation (hr after challenge): 24 , 48 hours after removal of the dressing according to the method of Draize (See table 1 in results and discussion free-text for details)

GENERAL
- The animals were observed at least once a day during the study in order to check for clinical signs and mortality.
- The animals were weighed individually on the day 0, 7, 14, 21 and 28.
- Necropsy: on day 28 Cutaneous samples were taken (one from each flank) from the challenge application site of each animal microscopically examined.

Positive control substance(s):

not specified

Results and discussion

Positive control results:

no data

Any other information on results incl. tables

PRELIMINARY STUDY:

- By intradermal route: Since the lowest concentration (1%) elicited a moderate erythema, it was decided to reduce the concentration to be applied at 0.1%. This concentration induced a very slight erythema.

- By cutaneous route: A very slight erythema was observed at 1%. This concentration was chosen for topical induction and for challenge.

MAIN STUDY:

- Clinical findings: Normal behaviour was observed in all animals, except in the two animals found dead, which were prostrated and diarrhoeicd before death.

- Mortality: Two males died: one on day 18, another on day 20.

- Body weight: No significant changes were observed in body weight gain.

- Necropsy: An epidermal densification (more or less marked) was found in 4 males and 5 females. These reactions are common in guinea-pigs and not significant. However, neither oedema nor sensitizing cellular features were observed.

- Scoring of cutaneous reactions: . At the end of induction period: Signs of irritation were observed on day 10 at the intradermal injection sites in control and treated groups. . After challenge application: Three males and five females exhibited a grade 1 (slight) erythema after 24h. This cutaneous reaction persisted in the same males and in only three females at the 48-hour examination time. No cutaneous reactions were observed in other animals.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Under the experimental conditions and according to the maximization method of Magnusson and Kligman, the test substance should not be considered as a skin sensitizer.

Executive summary:

The sensitation potential of Amines, N-tallow alkyltrimethylenedi-, propoxylated was tested in male an female guinea Pigs according to the Magnusson Kligmann method (comparable to OECD 406).

The test item was found not to be sensitising.

10 male and 10 female Dunkin-Hartley guinea pigs were exposed to the test item following the classical Magnusson Kligmann test design.

Findings:

- Clinical findings: Normal behaviour was observed in all animals, except in the two animals found dead, which were prostrated and diarrhoeicd before death.

- Mortality: Two males died: one on day 18, another on day 20.

- Body weight: No significant changes were observed in body weight gain.

- Necropsy: An epidermal densification (more or less marked) was found in 4 males and 5 females. These reactions are common in guinea-pigs and not significant. However, neither oedema nor sensitizing cellular features were observed.

- Scoring of cutaneous reactions:

At the end of induction period: Signs of irritation were observed on day 10 at the intradermal injection sites in control and treated groups.

After challenge application: Three males and five females exhibited a grade 1 (slight) erythema after 24h. This cutaneous reaction persisted in the same males and in only three females at the 48-hour examination time. No cutaneous reactions were observed in other animals.