Registration Dossier

Administrative data

Description of key information

Based on the results of the read across study, the test substance, 'iso and antesion C10-40 AAP EDM-ES' was determined to be non-sensitising to the skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Reason / purpose:
data waiving: supporting information
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
Refer to section 13 of IUCLID for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The in vivo study data were obtained in studies performed before any in vitro sensitization tests tests had been validated and accepted for regulatory purposes. Additionally, literature data demonstrates that an LLNA method is unreliable for surfactant substance, and may provide false positive results [1]. Therefore, an LLNA method is not deemed reliable for assessing the skin sensitisation of the substance.

[1]: Evaluating the sensitization potential of surfactants: Integrating data from the local lymph node assay, guinea pig maximization test, and in vitro methods in a weight-of-evidence approach. Ball et al. Regulatory Toxicology and Pharmacology 60 (2011) 389–400
Species:
guinea pig
Strain:
other: Pirbright-White
Sex:
male
Details on test animals and environmental conditions:
Test animals
- Age at study initiation: no data
- Weight at study initiation: 300 - 430 g
- Housing: max. 2 animals in one cage, Macrolon cages
- Diet: ad libitum; Ssniff-G (Alleindiät für Meerschweinchen), Ssniff Versuchstier-Diaten GmbH, 4770 Soest/Westfalen
- Water: ad libitum
- Acclimation period: 9 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 40-70
- Air changes (per hr): 10 per h
- Photoperiod: 12 h daily
Route:
intradermal
Vehicle:
water
Concentration / amount:
Dose range finding study: intradermal: 0.1%, 0.5%, 1%, 5%
Day(s)/duration:
1 d (24 h)
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Dose range finding study: epicutaneous: 5%, 20%, 50%, 100%
Day(s)/duration:
1 d (24 h)
Adequacy of induction:
not specified
Route:
intradermal
Vehicle:
water
Concentration / amount:
Main study: intradermal: 5%
Day(s)/duration:
2 d (48 h)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Main study: epicutaneous: 20%
Day(s)/duration:
2 d (48 h)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Challenge: epicutaneous: 5%
Day(s)/duration:
1 d (24 h)
Adequacy of challenge:
other: subirritative concentration based on pre-test
No. of animals per dose:
Range finding: 6 animals (4 epicutaneous, 2 intradermal)
Main Study: 10 animals (test group), 5 animals (control group)
Details on study design:
The test was performed according to a modified version of the Magnusson-Kligman Guinea Pig Maximisation Test. This investigation was performed according to HLD test plan P 3/152, 3-rd revision as well as according to the recommended guidelines of the USA Interagency Regulatory Liaison Group (IRLG, January, 1981).

Range finding tests:
Four animals were treated dermally in a preliminary study under occlusiv conditions (exposure period 24 h) with the following concentrations of the sample: epicutaneous: 5%, 20%, 50%. Reading 3 h p.a.
Two animals were treated intradermal: 0.1%, 0.5%, 1%, 5% (aqueous solution). Reading 24 h p.a.

Main study
(A) Induction exposure
(A.1) Intradermal injection – Performed on Test Day 1
Based on the pretest results, the test item concentration of 5% was selected for intradermal induction in the main study. An area of dorsal skin from the scapular region (approximately 6 x 8 cm) was clipped free of hair. Three pairs of intradermal injections (0.1 mL/site) were made just within the boundaries of a 4 x 6 cm area in the clipped region as follows:

- Test groups:
1) 0.1 mL Complete Adjuvant (50 % v/v in water for injection) (Bactoadjuvant Completa H 37 Ra, Difco Laboratories, Detroit, Michigan)
2) 0.1 mL 5 % v/v test substance in Aqua dest.
3) 0.1 mL 5 % v/v test substance in Aqua dest. emulsified in 50 % Adjuvant

- Control group:
1. 0.1 mL Complete Adjuvant (50 % v/v in water for injection)
2. 0.1 mL aqua dest
3. 0.1 mL Complete Adjuvant (50 % v/v in aqua dest.)

(A.2) Epidermal induction - Performed one week after intradermal injection
- Volume: 0.5 mL
- Exposure period: 48 h
- Test groups: 10
- Control group: 5
- Site: the same site as for intradermal injection
- Frequency of applications: 1
- Concentrations: 20%
(B) Challenge exposure
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after induction
- Exposure period: 24 h
- Control group: aqua dest.
- Concentrations: 5 %
- Evaluation (h after challenge): 48 h, 72 h
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no skin reaction
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no skin reaction
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no skin reaction
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no skin reaction
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
other: GHS criteria not met
Conclusions:
Based on the results of the read across study, a similar non-sensitising behaviour can be expected for the test substance.
Executive summary:

A study was conducted to determine skin sensitisation potential of the read across substance, 'C11-unsatd. AAP TMA-MS' (active: 47%) in a guinea pig maximisation test (GPMT), according to a method similar to OECD Guideline 406. The test was performed in 15 (10 test and 5 control) male young adult Pirbright-White guinea pigs. The maximum compatible concentrations which led to slight irritation after intradermal and dermal application as well as the sub-irritative dose for the challenge application were determined in pre-tests. In the main test, one treated group of ten males received the test substance in a 50% mixture of Complete Adjuvant (50 % v/v in water for injection) on Day 1 by intradermal injections in the interscapular region at the concentration of 5% and on Day 8 by topical application to the clipped interscapular region at 20% (aqueous solutions). A control group of five males received water (vehicle) on Day 1 and Day 8 to the interscapular region. The induction phase was followed by a 14 d rest period. For challenge test, the test substance was applied topically on Day 22 to the posterior right flank at 20%. Cutaneous reactions were evaluated 48 and 72 h after challenge test. The sensitisation rate, i.e. the number of animals showing an allergic response expressed as a percentage of the total number of animals, was calculated. No allergic skin reactions were observed in test animals 48 and 72 h after the challenge exposure. No findings were observed in control animals. Therefore, the sensitisation rate was determined to be 0% for test substance. Under the study conditions, the read across substance was concluded to be non-sensitising to the skin of guinea pigs (Meisel, 1983). Based on the results of the read across study, a similar non-sensitising behaviour can be expected for the test substance, 'C18-unsatd and C22-unsatd. AAP EDM-ES'.

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

A study was conducted to determine skin sensitisation potential of the read across substance, 'C11-unsatd. AAP TMA-MS' (active: 47%), using Guinea Pig Maximisation test (GPMT), according to the method similar to the OECD Guideline 406, incompliance with GLP. The maximum compatible concentrations which led to slight irritation after intradermal and dermal application as well as the sub-irritative dose for the challenge application were determined in pre-tests. In the main test, one treated group of ten males received the test substance in a 50% mixture of Complete Adjuvant (50 % v/v in water for injection) on Day 1 by intradermal injections in the interscapular region at the concentration of 5% and on Day 8 by topical application to the clipped interscapular region at 20%. A control group of five males received water (vehicle) on Day 1 and Day 8 to the interscapular region. The induction phase was followed by a 14 d rest period. For challenge test, the test substance was applied topically on Day 22 to the posterior right flank at 20%. Cutaneous reactions were evaluated 48 and 72 h after challenge test. The sensitisation rate, i.e. the number of animals showing an allergic response expressed as a percentage of the total number of animals, was calculated. No allergic skin reactions were observed in test animals 48 and 72 h after the challenge exposure. No findings were observed in control animals. Therefore, the sensitisation rate was determined to be 0% for test substance. Based on the study results, the study author concluded that the test substance was non skin sensitiser. Under the study conditions, the test substance was determined to be non-sensitising to skin (Meisel, 1983). Based on the results of the read across study, similar absence of skin sensitisation potential is exected for the test substance, 'iso and anteiso C10-40 AAP EDM-ES'.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results of read across GPMT study, the test substance, 'iso and anteiso C10 -40 AAP EDM-ES', does not warrant classification for skin sensitisation, according to the EU CLP criteria (Regulation 1272/2008/EC).