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Toxicological information

Endpoint summary

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Description of key information

Based on the results of the read across studies, the test substance is not considered to sensitising to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Buehler test
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From May 02, 2005 to October 04, 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Literature data demonstrates that an LLNA method is unreliable for surfactant substance, and may provide false positive results.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Test animals
- Source: Elm Hill Breeding Labs, Chelmsford, MA, USA
- Age at study initiation: Young adult animals
- Weight at study initiation: 327-399 g
- Housing: The animals were group housed in suspended stainless steel caging with mesh floors or plastic perforated bottom caging which conform to the size recommendations according to ‘Guide for the care and use of laboratory animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times/wk.
- Diet: Pelleted Purina guinea pig chow # 5025, ad libitum
- Water: Filtered tap water, ad libitum
- Acclimation period: 3-17d

Environmental conditions
- Temperature: 19-22°C
- Humidity: 31-58%
- Photoperiod (hrs dark / hrs light): 12-h light/dark cycle

In-life dates: From: May 2, 2005 to: June 10, 2005
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 1% w/w mixture of the test substance in distilled water (0.4 mL)
Challenge: 0.25% w/w mixture of the test substance in distilled water (0.4 mL)
Day(s)/duration:
6h exposure, observations 24 and 48h after exposure
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 1% w/w mixture of the test substance in distilled water (0.4 mL)
Challenge: 0.25% w/w mixture of the test substance in distilled water (0.4 mL)
Day(s)/duration:
6h exposure, observations 24 and 48h after exposure
No. of animals per dose:
20 animals in the test substance group and 10 animals in the control group
Details on study design:
Range finding tests:
A preliminary irritation study was performed to determine the highest non-irritating concentration. 8 guinea pigs (5 males and 3 females) were exposed for 6 h period to various concentrations of the test substance as follows: 100, 75, 50, 25, 1.25, 1.0, 0.75, 0.25 and 0.10%.w/w in distilled water. The fur was removed by clipping the dorsal area and flanks of each guinea pig. The area was divided into two or four test sites on each animal. Two to four concentrations of the test substance were applied to the sites. 0.4 mL of each concentration was applied to a test site using a 25 mm Hill Top Chamber. The test sites were wrapped with non-allergenic adhesive tape. All animals were evaluated at approximately 24 hours, 2 days and one animal on Day 5. Each site was evaluated for erythema.

Main study
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6h
- Test groups: One test group, including 20 guinea pigs
- Control group: No control animals were employed in induction phase
- Site: Left side of each animal
- Frequency of applications: Once a week for three consecutive weeks
- Duration: 6 h/application
- Concentrations: 1 % w/w mixture of the test substance in distilled water (0.4 mL)
- Procedure for application: Once a week for three weeks, 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. Due to residual irritation from the previous doses, the dose site was moved each induction. Approximately 24 and 48h after each induction exposure, the skin was evaluated for local reactions (erythema).

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Twenty-seven days after the first induction dose
- Exposure period: 6h
- Test groups: One test group (20 animals) exposed with 0.25% w/w mixture of the test substance in distilled water
- Control group: One naive control group (10 animals) exposed with 0.25% w/w mixture of the test substance in distilled water
- Site: The test substance was applied to a naïve site on the right side of each test animal.
- Concentrations: 0.25% w/w mixture of the test substance in distilled water
- Evaluation (hr after challenge): These sites were evaluated for a sensitisation response approximately 24 and 48h after the challenge exposure.

Other: Historical Positive Control Validation Study: The procedures used in this study were validated using alpha-Hexylcinnamaldehyde Technical (HCA) grade as a positive control substance. A positive control validation study is run at no less than six months intervals at the testing laboratory. The results from the most recent positive control validation study performed on March 2005 are provided in the study report.
Challenge controls:
10 naive animals exposed with 0.25% w/w mixture of the test substance in distilled water
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamaldehyde
Positive control results:
Induction: Very faint to faint erythema (0.5-1.0) was noted for all of the positive control sites during the induction phase.
Challenge: Four of nine positive control animals exhibited signs of skin sensitisation response 24 and 48h after exposure. Very faint erythema was observed for four other sites after challenge. Very faint erythema was observed in three of five positive control naive test sites after 24h. Irritation persisted at one of these sites through 48h.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.25% w/w mixture of the test substance in distilled water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No animals with positive response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.25% w/w mixture of the test substance in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No animals with positive response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.25% w/w mixture of the test substance in distilled water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No animals with positive response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.25% w/w mixture of the test substance in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No animals with positive response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
75% w/w alpha-Hexylcinnamaldehyde (HCA) in mineral oil
No. with + reactions:
8
Total no. in group:
9
Remarks on result:
positive indication of skin sensitisation

Summary of results in the main study:

- Induction Phase: Very faint to faint erythema (0.5-1.0) was observed for all sites during the induction phase.

- Challenge Phase: 

Test group: None of the test animals exhibited a positive skin sensitisation response (score greater than 0.5) at 24 or 48h after challenge. Very faint erythema (0.5) was noted in 9 out of 20 test animals at 24h after challenge. Similar irritation persisted at two sites through 48h.

Naive Control group: Very faint erythema (0.5) was observed in 5 out of 10 test animals at 24h after challenge. Similar irritation persisted at two sites through 48h.

Table 1. The severity index of test and control group

Treatment

Severity

24 h

48 h

Test

0.23

0.05

Control

0.25

0.10
Interpretation of results:
other: CLP criteria not met
Remarks:
(non sensitising)
Conclusions:
Under the study conditions, the read across substance was determined to be non-sensitising in a Buehler test when applied topically to albino Hartley guinea pigs.
Executive summary:

A study was conducted to determine the skin sensitisation potential of the read across substance, C12-16 ADBAC (80.9% active in water/alcohol) 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 read across 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 read across 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 read across 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 read across substance was determined to be non-sensitising when applied topically to albino Hartley guinea pigs (Durando, 2005). Based on the results of the read across study, a similar non-sensitising potential can be expected for the test substance.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Modified Draize test
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Cited as Directive 84/449/EEC, B.6
Deviations:
no
GLP compliance:
no
Type of study:
other: Modification of the Draize technique (Draize, Woodward and Calvery 1944 NAS-NRC 1964).
Justification for non-LLNA method:
The Local Lymph Node Assay (LLNA; TG 429) was adopted in 2002.
Species:
guinea pig
Route:
intradermal
Vehicle:
water
Concentration / amount:
Induction 0.1% intracutaneous
Challenge 0.1% intracutaneous
Day(s)/duration:
1 day
Route:
intradermal
Vehicle:
water
Concentration / amount:
Induction 0.1% intracutaneous
Challenge 0.1% intracutaneous
Day(s)/duration:
1 day
No. of animals per dose:
6
Details on study design:
- 1st application: Induction 0.1 % intracutaneous
- 2nd application: Challenge 0.1 % intracutaneous
For the induction phase, 0.1 mL of a concentration of 0.1% of test substance in water was injected intradermally into the back of each six guinea pigs. This procedure was repeated every other days, using a different injection site on each occasion, until a total of nine injections had been given. Injection sites were examined 24h after each injection and scored for erythema and oedema using the Draize scale.
After completion of this series of priming injections the animals remained untreated for two weeks, and were then given a single challenge intradermal injection of the same concentration and volume as for induction. Injection sites were examined 24h 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.
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
Remarks on result:
other: See 'Any other information on results incl. tables'
Key result
Reading:
1st reading
Group:
negative control
Remarks on result:
not measured/tested
Key result
Reading:
1st reading
Group:
positive control
Remarks on result:
not measured/tested

Modified Draize test:

- The priming injections elicited very slight to well defined erythema, and very slight to slight oedma on all occasions.
- The challenge dose produced a well defined erythema and very slight oedema in all occasions.

As the challenge doses did not produce any greater reaction in any animal, it may be concluded that is not a sensitising
agent under the conditions of this experiment.

For result tables, kindly refer to the attached background material section of the IUCLID.

Interpretation of results:
other: CLP criteria not met
Remarks:
(non sensitising)
Conclusions:
Under the study conditions, the read across substance was not considered sensitizing to guinea pig skin.
Executive summary:

A study was conducted to determine the skin sensitisation potential of the read across substance, C12 -16 ADBAC (50% active in water) according to EU Method B.6 (modified Draize test). For the induction phase, 0.1 mL of 0.1% read across 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 read across substance was not considered sensitizing to guinea pig skin (Thomas, 1974). Based on the results of the read across study, a similar non-sensitising potential can be expected for the test substance.

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

Study 1: A study was conducted to determine the skin sensitisation potential of the read across substance, C12 -16 ADBAC (50% active in water) according to EU Method B.6 (modified Draize test). For the induction phase, 0.1 mL of 0.1% read across 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 read across substance was not considered sensitizing to guinea pig skin (Thomas, 1974).

Study 2: A study was conducted to determine the skin sensitisation potential of the read across substance, C12 -16 ADBAC, 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. Based on the results of the read across study, the test substance is considered to be non-sensitising when applied topically to albino Hartley guinea pigs (Durando, 2005). Based on the results of the read across study, a similar non-sensitising potential can be expected for the test substance.

The biocides assessment reports available from RMS Italy 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). 

Overall, based on the available information from the read across studies and in line with the biocides assessment report, the test substance is considered to be non-sensitising to the skin.   


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results of the read across studies, the test substance does not warrant a classification for the skin sensitisation endpoint, according to the EU CLP criteria (Regulation EC 1272/2008).