Registration Dossier

Administrative data

Endpoint:
respiratory sensitisation
Data waiving:
other justification
Justification for data waiving:
other:
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Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
appearance / physical state / colour
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 21, 2006 to February 19, 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OPPTS 830.6303 (Physical State)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 830.6302 (Color)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 830.6304 (Odor)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
- Purity 94.4% (LC-MS/MS)
Physical state at 20°C and 1013 hPa:
solid
Key result
Form:
solid: crystalline
Remarks:
tenacious and sticky
Colour:
white
Odour:
other: faint, marzipan-like odour
Substance type:
organic

The test substance is hygroscopic

Conclusions:
Under the study conditions, the substance was a crystalline, hygroscopic, sticky white solid with a faint marzipan-like odour at 20ºC.
Executive summary:

A study was conducted to determine the appearance, physical state and colour of the test substance according to EPA OPPTS 830.6302, .6303 and .6304, in compliance with GLP. Under the study conditions, the substance was a crystalline, hygroscopic, sticky white solid with a faint marzipan-like odour at 20ºC (Schulze, 2007).

Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
vapour pressure
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From March 15, 2012 to March 19, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 104 (Vapour Pressure Curve)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method A.4 (Vapour Pressure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 830.7950 (Vapor Pressure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of method:
effusion method: by loss of weight or by trapping vaporisate
Specific details on test material used for the study:
- Molecular formula: Cn+9 H2n+14 N Cl (n=12-16)
- Molecular weight: 352.5
- Substance type: Solid
- Physical state: White powder with lumps (determined at NOTOX)
- Analytical purity: 99.24 ± 0.676 % w/w
- Method used for analysis: LC-MS/MS and GC-MS (external standard)
- Composition of test material, percentage of components: Refer to the attached background materail for details
- Purity test date: 26 October, 2011
- Lot/batch No.: 667S0002
- Expiration date of the lot/batch: 30 April, 2012
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark in desiccator
- Study specific test substance information: Freeze dried Arquad sample MCB-50 EP, stored in desiccator above P2O5 and substance was handeled in nitrogen environment in glovebox
- Other:
- Chemical name: Benzyl(C12-C16-alkyl)dimethylazanium chloride
Key result
Temp.:
20 °C
Vapour pressure:
0.002 Pa
Remarks on result:
other: The value of vapour pressure is < 0.0015 Pa
Temp.:
20 °C
Vapour pressure:
0 mm Hg
Remarks on result:
other: The value of vapour pressure is < 0.000011 mm Hg
Key result
Temp.:
25 °C
Vapour pressure:
0.006 Pa
Remarks on result:
other: The value of vapour pressure is < 0.0058 Pa
Temp.:
25 °C
Vapour pressure:
0 mm Hg
Remarks on result:
other: The value of vapour pressure is < 0.000043 mm Hg

Formulas used:

Evaporation rate: (νT) =Dm/ F x t [g/cm /h]

where:

Dm = weight loss of the test substance [g]

F = surface of the sample plate [cm2]

t = elapsed time for the weight loss [h]

Vapour pressure equation log PT=c lognT+d

where:

c = constant specific for the experimental arrangement

d = constant specific for the experimental arrangement

Vapour pressure regression curve log PT=a 1/T+b

where:

T = temperature [K]

a = slope [K]

b = intercept

Results:

The isothermal TGA effusion method was applied for the determination of the vapour pressure of the test substance is:

The vapour pressure of the test substance at 20°C (293K) and 25°C (298K) was:

 

20°C

25°C

[Pa]

[mmHg]

[Pa]

[mmHg]

Test substance

< 1.5 x10-3

< 1.1 x10-5

< 5.8 x10-3

< 4.3 x10-5

Conclusions:
Under the study conditions, the vapour pressure of test substance was found to be <1.5E-03 Pa at 20°C and <5.8E-03 Pa at 25°C (isothermal thermo gravimetric effusion method).

Executive summary:

A study was conducted to determine the vapour pressure of the test substance according to OECD Guideline 104, EU Method A.4 and EPA OPPTS 830.7950 (isothermal thermo gravimetric effusion method), in compliance with GLP. Approximately 14.5 or 15.2 mg of the test substance was applied to the surface of a roughened glass plate as a homogeneous layer. The plates were dried at 30°C under nitrogen in the thermogravimetric analyzer (TGA). The weight loss of the test substance was measured continuously as a function of time. Benzo(ghi)perylene, chrysene, hexachlorobenzene, naphthalene and water were used as reference substances for validation. The log Vt, 20 value which was obtained by extrapolation of the evaporation rate curve, fitted in the vapour pressure regression curve. Under the study conditions, the vapour pressure of test substance was found to be <1.5E-03 Pa at 20°C and <5.8E-03 Pa at 25°C (Brekelmans, 2012).

Reason / purpose:
data waiving: supporting information
Reference

The test substance is not considered to be sensitising.

Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Study 1. A study was conducted to determine the skin sensitisation potential of the test substance according to OECD Guideline 406 and US EPA OPPTS 870.2600 (Buehler test), in compliance with GLP. The study was conducted in two phases, with induction and challenge exposures. To determine the highest non-irritating concentration (HNIC) for the challenge phase, a preliminary irritation study was performed with 8 guinea pigs. The concentrations used were 100, 75, 50, 25, 1.25, 1.0, 0.75, 0.25 and 0.10%. w/w in distilled water. After treatment, the application sites were evaluated and scored. During the induction phase of the main study, 0.4 mL of a 1% w/w mixture of the test substance in distilled water was applied to the left side of each animal, once per week for three weeks. Twenty-seven days after the first induction dose, 0.4 mL of a 0.25% w/w (HNIC) mixture of the test substance in distilled water was applied to a naïve site on the right side of each test animal for challenge exposure. Ten additional animals exposed with 0.25% w/w mixture of the test substance in distilled water served as naive control group in the challenge phase only. Approximately 24 and 48 h after each induction and challenge dose, the animals were scored for erythema. Very faint to faint erythema (0.5 to 1) was observed in all test animals during induction. None of the test animals exhibited a positive skin sensitisation response (score greater than 0.5) at 24 or 48 h after challenge. Under the test conditions, the test substance was determined to be non-sensitising when applied topically to albino Hartley guinea pigs (Durando, 2005).

Study 2. A study was conducted to determine the skin sensitisation potential of the test substance according to EU Method B.6 (modified Draize test). For the induction phase, 0.1 mL of 0.1% test substance in water was injected intradermally into the back of each six guinea pigs. This procedure was repeated every other day, using a different injection site on each occasion, until a total of nine injections had been given. Injection sites were examined 24 h after each injection and scored for erythema and oedema using the Draize scale. After a two week interval, a single challenge intradermal injection of the same concentration and volume was given as for induction. Injection sites were examined 24 h after this challenge dose as before for erythema and oedema. The effects were compared to those produced by the priming doses in order to determine whether sensitisation had been produced. The priming injections elicited very slight to well defined erythema, and very slight to slight oedema on all occasions. The challenge dose produced a well-defined erythema and very slight oedema in all occasions. However, the challenge doses did not produce any greater reaction in any animal. Under the study conditions, the test substance was not considered sensitizing to guinea pig skin (Thomas, 1974).

Study 3. A study was conducted to determine the skin sensitisation potential of the test substance according to the Magnusson and Kligman method (guinea pigs maximisation test). Female albino guinea pigs received on Day 1 an intracutaneous injection of 0.1 mL of 0.1% test substance in isotonic saline with Freund's complete adjuvant (1:1) on the shaved part of the flank (approximately 6 x 4 cm). On Day 7, animas were applied an epicutaneous occlusive application for 48 h with 0.3 mL of 0.1% test substance in ethylene glycol monomethylether, water, Tween 80 (180/180/40) v/v. Finally, on Day 21, guinea pigs were challenged epicutaneously (open application) with 0.05 mL of test substance in water at the shaved ventral side of the animal. The response was monitored after 24 and 48 h next to a control group of 10 animals. Concentrations were previously ascertained by both intracutaneous and epicutaneous applications to determine irritation potential in three animals at 24 and 48 h, respectively. In all cases non-irritating concentrations were chosen. At 24 h after challenge, 4/20 animals showed a positive response consisting of slight erythema. After 48 h, 2/20 animals showed a slight macular erythema. Under the conditions of this study, the test substance was negative for skin sensitization (Schallreuter, 1996).  

Study 4. A study was conducted to determine the skin sensitisation potential of the test substance in albino guinea pigs. Five test animals were used for the study. The concentration of the test substance for the induction and challenge phases were an intradermal induction with 10 injections of 0.1% in water every alternate intradermal and a challenge with 1 injection of 0.1% in water two weeks after the 10th induction injection. Very slight erythema and oedema were noted 24 h after challenge, but these reactions after challenge were not substantially different from those after the induction injections. Under the study conditions and although the number of test animals was limited, the test substance was considered as a non-sensitising to guinea pig skin (Anonymous, 1969).

Study 5. A study was performed to assess the skin sensitisation potential of the test substance in the albino guinea pig. Ten male test animals were used for the study. The concentration of the test substance for the induction and challenge phases were first an epicutaneous induction of 8 applications of 0.1% in water every day and then an epicutaneous challenge of 1 application of 0.1% in water two weeks after the 8th induction application. No skin reactions were noted 24 h after the first induction application and 24 h after challenge. Under the study conditions and although the number of test animals was limited, the test substance was considered as a non-sensitising to guinea pig skin (Hixson, 1968).

Study 6. Studies were conducted to determine the skin sensitisation potential of the test substance. Basketter (1996) compared the results obtained with various substances, including the present test substance, in an LLNA assay, a guinea pig maximisation test (GMPT) and a Buehler test. Although the test substance was evaluated as non-sensitising in the guinea pig test, the LLNA result was positive. The LLNA test however, can give false positive results for strong irritants (as does the GPMT test), as was demonstrated by the non-sensitising irritant sodium dodecyl sulphate which was tested positive in the LLNA. In order to evaluate possible false-positive results, a range of non-sensitising irritant chemicals, including the test substance were tested in the LLNA. The stimulation index for the test substance did not exceed the factor 3 and thus the outcome was considered negative (Basketter, 1998). Under the study conditions and based on the literature data of LLNA, the test substance was not considered to be a skin sensitiser (Basketter, 1996 and 1998).

Endpoint conclusion:
no study available

The available in vivo skin sensitisation studies suggest that the test substance is not a skin sensitiser and therefore no classification is required for this endpoint according to CLP (EC 1272/2008) criteria.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion