Quaternary ammonium compounds, benzyl C12-C16 (even numbered)-alkyldimethyl chlorides

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

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

Guideline:

EPA OPPTS 830.6303 (Physical State)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.6302 (Color)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.6304 (Odor)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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

Due to the hygroscopic behaviour the substance deliquesced when it was bought to air for several minutes.

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).

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

The vapour pressure was determined using the isothermal thermo gravimetric effusion method according to OECD Guideline 104, EU Method A.4 and EPA OPPTS 830.7950 (Brekelmans, 2012).

Vapour pressure:

0.006 Pa

at the temperature of:

25 °C

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Based on the available information and in line with the biocides assessment report, the test substance is non-sensitising to the skin.  

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Study 1: A modified Draize test was conducted to determine the skin sensitisation potential of the test substance, C12 -16 ADBAC (50% active in water) according to EU Method B.6. For the induction phase, 0.1 mL of 0.1% test substance in the 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 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 well-defined erythema and very slight oedema on 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 2: A Buehler test was conducted to determine the skin sensitisation potential of the test substance, C12-16 ADBAC (80.9% active in water/alcohol) according to OECD Guideline 406 and US EPA OPPTS 870.2600, 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 3: A guinea pigs maximisation test (GPMT) was conducted to determine the skin sensitisation potential of the test substance, C12 -16 ADBAC (purity not specified) according to the Magnusson and Kligman method. 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, animals have 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 the 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 similar to a GPMT was conducted to determine the skin sensitisation potential of the test substance, C12-16 ADBAC (50% active in water) 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 day 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 the challenge, but these reactions after the 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 similar to the Buehler test was performed to assess the skin sensitisation potential of the test substance, C12-16 ADBAC (0.1% active in water) 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 the 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).

Two more skin sensitisation studies (Basketter 1996, 1998) were identified for the test substance, C12-16 ADBAC (purity not specified) from literature sources, which compared the skin sensitisations results obtained from standard guinea pig tests with Local lymph mode assay (LLNA). The Basketter (1996) study compared the results obtained with various substances, including the present test substance, in an LLNA assay, a GPMT and a Buehler test. Although the test substance was evaluated as non-sensitising in the guinea pig test, the LLNA result was positive. As per the study authors, 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. To evaluate possible false-positive results, a range of non-sensitising irritant chemicals, including the test substance were tested in the LLNA (Basketter, 1998). The stimulation index for the test substance did not exceed the factor 3 and thus the outcome was considered negative by the study authors. 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).

Also, the Biocides assessment report on C12-16 ADBAC, published by the Italian authorities in June 2015, concluded that the test substance is not a skin sensitiser under the experimental conditions tested. Although no experimental data is available, C12-16-ADBAC/BKC is not expected to be a respiratory sensitizer (ECHA biocides assessment report, 2015).

Therefore, based on the available information and in line with the biocides assessment report, the test substance is non-sensitising to the skin.  

Endpoint conclusion:

no study available

Additional information:

As per the Biocides assessment report on C12-16 ADBAC, published by the Italian authorities in June 2015, although no experimental data is available, C12-16-ADBAC is not expected to be a respiratory sensitizer (ECHA biocides assessment report, 2015).

Based on the absence of skin sensitisation responses in available in vivo studies, the test substance does not warrant a classification for the skin sensitisation endpoint, according to the EU CLP criteria (Regulation EC 1272/2008).