Registration Dossier

Administrative data

Description of key information

Based on the available weight of evidence information from studies for substances representative of the main constituents, the test substance isconsidered to be non-sensitising to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
From May 25, 2005 to June 13, 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 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:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA:J
Sex:
female
Details on test animals and environmental conditions:
Source: Jackson Laboratories
Acclimation: 5 days
Number of animals: 37 females (nulliparous and non-pregnant)
Body weight: 16 - 21g
Body weight variation was within +/- 20% of the sex mean.
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle.
Diet: Fresh PMI (Diet #5001)
Water: free access to tap water.
Vehicle:
other: Ultrapure liquid petrolatum
Concentration:
0, 2.5, 5, 10 and 25% w/w
No. of animals per dose:
5
Details on study design:
The test substance concentrations selected for the main study were based on the results of a pre-screen test. In the main study, four experimental groups of five female CBA/J mice were treated with test substance concentrations of 2.5, 5, 10 or 25% w/w for three consecutive days, by topical application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone (Liquid petrolatum). A positive control group with a-hexylcinnamaldehyde (HCA - 50%) was also included in the experiment. Five days after the last exposure, all animals were injected with 5-bromo-2'-deoxy-uridine (BrdU) and the draining (auricular) lymph nodes were then isolated and pooled for each animal. Cells were fixed using 70% ethanol and used for the measurement of the cell number and the BrdU determination (percentage of proliferating cells in "S" phase). Flow cytometry was conducted for analysis and stimulation index (SI) was recorded
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
SI
Positive control results:
The SI value calculated for the positive control was 9.6 and ear swelling was observed in this group.
Key result
Parameter:
SI
Value:
ca. 0.9
Variability:
+/- 0.7
Test group / Remarks:
2.5%
Key result
Parameter:
SI
Value:
ca. 0.9
Variability:
+/- 0.6
Test group / Remarks:
5%
Key result
Parameter:
SI
Value:
ca. 0.7
Variability:
+/- 0.3
Test group / Remarks:
10%
Key result
Parameter:
SI
Value:
ca. 0.3
Variability:
+/- 0.1
Test group / Remarks:
25%
Cellular proliferation data / Observations:
- SI values were similar among the control and test groups and were below 3. Three concentrations (i.e.2.5, 5 and 25%) induced ear swelling.
- No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.
Interpretation of results:
other: not classified based on EU CLP criteria
Conclusions:
Based on the results of the read across study, the test substance, is considered to be non-sensitiser to the skin.
Executive summary:

A study was conducted to determine the skin sensitisation potential of the read across substance, 'Reaction mass of mono- and di- hexadecyl phosphate esters, potassium salts and phosphoric acid' (98.5%) according to OECD Guideline 429 and US EPA OPPTS 870.2600 (LLNA), in compliance with GLP. The read across substance concentrations selected for the main study were based on the results of a pre-screen test. In the main study, four experimental groups of five female CBA/J mice were treated with read across substance concentrations of 2.5, 5, 10 or 25% w/w for three consecutive days, by topical application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone (Liquid petrolatum). A positive control group with a-hexylcinnamaldehyde (HCA - 50%) was also included in the experiment. Five days after the last exposure, all animals were injected with 5-bromo-2'-deoxy-uridine (BrdU) and the draining (auricular) lymph nodes were then isolated and pooled for each animal. Cells were fixed using 70% ethanol and used for the measurement of the cell number and the BrdU determination (percentage of proliferating cells in "S" phase). Flow cytometry was conducted for analysis and stimulation index (SI) was recorded. Mortality/viability, body weights, clinical signs, ear size and irritation (and other local effects) were recorded as well. SI values were similar among the control and test groups and were below 3. Three concentrations (i.e.2.5, 5 and 25%) induced ear swelling. No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period (MBRL, 2005). Based on the results of the read across study, the test substance is considered to be non-sensitising to the skin.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
From March 24, 1998 to April 24, 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The epicutaneous induction and challenge were performed under semi-occlusive conditions.
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:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
epicutaneous induction and challenge performed under semi-occlusive conditions
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
yes
Remarks:
epicutaneous induction and challenge performed under semi-occlusive conditions
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid GPMT study was available before REACH came into force, therefore no additional LLNA study was conducted.
Species:
guinea pig
Strain:
Himalayan
Sex:
female
Details on test animals and environmental conditions:
Test animals
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: 416 ± 23 g (mean ± SD, control group); 434 ± 24 g (mean ± SD, treatment group)
- Housing: animals were housed in groups of 5 in labelled metal cages with wire-mesh floors (ITL, Bergen, the Netherlands)
- Diet: standard guinea pig diet (LC 23-B, pellet diameter 4mm, including ascorbic acid (1600 mg/kg); Hope farms, Woerden, the Netherlands), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 d

Environmental conditions
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

In-life dates: From: 24 March 1998 To: 24 April 1998
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Day 1:
Intradermal: undiluted and 50% in 1:1 mixture (w/w) with FCA with water for injection

Epicutaenous:
Day 8: undiluted test substance
Day(s)/duration:
Day 1 and Day 8
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Intradermal:
Day 1 (3 pairs of injections, 0.1 mL/site): 1:1 mixture (w/w) FCA/water, corn oil, corn oil (w/v) in a 1:1 mixture (w/w) FCA (final concentration is 50% corn oil)

Epicutenous
Day 8: 0.5 mL corn oil
Day(s)/duration:
Day 1 and Day 8
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Day 1:
Intradermal: 5% solution of positive control substance

Day 8:
Epicutaneous: undiluted positive control substance
Day(s)/duration:
Day 1 and Day 8
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Test substance undiluted
Day(s)/duration:
Day 21
Adequacy of challenge:
highest non-irritant concentration
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
Control substance: Corn oil
Day(s)/duration:
Day 21
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
5 and 10% positive control substance solution
Day(s)/duration:
Day 21
No. of animals per dose:
10 (treatment group)
5 (control group)
Details on study design:
Range finding test:
Prior to the start of the main study, the intradermal and epidermal irritancy of the test substance was investigated to select suitable concentrations for the induction and challenge phase of the main study. The selection was based on the absence of toxicity and on the following criteria for each route and/or study phase:
Induction (intradermal and epidermal): The highest possible concentration that produced moderate irritation (the intradermal reactions may include slight necrosis (< 3 mm in diameter)).
Challenge: The maximum non-irritant concentration.

A series of test substance concentrations were tested. The first and subsequent concentrations were selected from the series: 100% (undiluted), 50%, 20%, 10%, 5%, 2%, 1% and if needed, further lower concentrations using the same steps. The test system and procedures were identical to those used during the main study, unless otherwise specified. The four animals were 5-9 weeks old. The body weights were determined prior to treatment (results not shown).

Intradermal Injections:
A series of four test substance concentrations was used; the highest concentration was the maximum concentration that could technically be injected (undiluted). One animal received 50 and 100% (undiluted), and the second animal received 10 and 20%, respectively, in duplicate (0.1 mL/site) in the clipped scapular region. The injection sites were assessed for irritation 24 and 48 h after treatment. Slight erythema was observed at the injection site of the undiluted test substance 48 h after exposure. The undiluted test substance was selected for the induction phase in the main study.

Epidermal application:
A series of four test substance concentrations (10, 20, 50 and 100%) was used. All concentrations could technically be applied. Two different concentrations were applied (0.5 mL each) per animal to the clipped flank, using Metalline patches (2x3 cm) mounted on Medical tape, which were held in place with Micropore tape and subsequently Coban elastic bandage (semi-occlusive covering). The animals receiving intradermal injections were treated with the lowest concentrations (10 and 20%) and two further animals with the highest concentrations (50 and 100%). After 24 h, the dressing was removed and the skin cleaned of residual test substance. The treated skin areas were assessed for irritation 24 and 48 h after exposure. No skin irritation was observed at any of the treated sites at any of the reading time points. As the epidermal induction using the test substance did not cause any skin irritation, the test site of all animals was treated with 10% SDS approximately 24 h before the epidermal induction in the main study, to provoke a mild inflammatory reaction. The undiluted test substance was selected for the challenge phase in the main study.

Main study
A) Induction exposure
- No. of exposures: 2, intradermal and epicutaneous
- Exposure period: single injection (epidermal) and 48 h (epicutaneous)
- Test groups:
Intradermal, Day 1 (3 pairs of injections, 0.1 mL/site):
Injection 1: a 1:1 mixture (w/w) Freunds Complete Adjuvant (FCA)/water for injection
Injection 2: undiluted test substance
Injection 3: undiluted test substance in a 1:1 mixture (w/w) with FCA (final concentration is 50% test substance)
48 h after intradermal injection (Day 3), the degree of erythema and edema was evaluated.

On Day 7, the scapular area between the injection sites was clipped and subsequently rubbed with 10% sodium dodecyl sulfate in vaseline using a spatula. This concentration of SDS provoked a mild inflammatory reaction.

Epicutaneous, Day 8:
0.5 mL undiluted test substance was applied to the SDS-treated skin area. The semi-occlusive dressing was kept in place for 48 h. The degree of erythema and edema was evaluated directly after cleaning the skin area with water (Day 10).

- Control group:
Intradermal, Day 1 (3 pairs of injections, 0.1 mL/site):
Injection 1: a 1:1 mixture (w/w) FCA/water
Injection 2: corn oil
Injection 3: corn oil (w/v) in a 1:1 mixture (w/w) FCA (final concentration is 50% corn oil)

On Day 7, the scapular area between the injection sites was clipped and subsequently rubbed with 10% sodium dodecyl sulfate (SDS, Boom, Meppel, the Netherlands) in vaseline using a spatula. This concentration of SDS provoked a mild inflammatory reaction.

Epicutaneous, Day 8: 0.5 mL corn oil

- Site: the shoulder region
- Frequency of applications: once (intradermal on Day 1 and epicutaneous on Day 8)
- Duration: Day 1 (intradermal), Day 8-10 (epicutaneous)
- Concentrations: undiluted (intradermal and epicutaneous)

B) Challenge exposure
- No. of exposures: 1 (challenge)
- Day(s) of challenge: 21
- Exposure period: 24 h
- Test groups: 0.5 mL test substance
- Control group: 0.5 mL test substance
- Site: approximately 20 mm x 30 mm, on one flank of the animals
- Concentration: undiluted
- Evaluation (h after challenge): 24 and 48 h after the challenge ended
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamicaldehyde, tech. 85%
Positive control results:
A reliability check is carried out at regular intervals with alpha-hexylcinnamic aldehyde to check the sensitivity of the test system and the reliability of the experimental methods used by the test laboratory. In an independent study performed in 1998 (report No. 217812), alpha-hexylcinnamic aldehyde induced sensitisation in 80% (8/10) of the Himalayan guinea pigs challenged with a 10% solution, and in 70% (7/10) of the guinea pigs challenged with a 5% solution. A 5% solution was used for intradermal induction and undiluted test substance was used for topical induction.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10% solution
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Sensitisation
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
5% solution
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
Sensitisation
Remarks on result:
positive indication of skin sensitisation

48 h after intradermal induction, slight to severe erythema was noted at all of the sites injected with FCA/water and FCA/test substance in 10/10 treated and 5/5 control animals. 4/5 control animals also exhibited necrosis at the FCA/test substance injection site. In 3/10 treated animals slight to well-defined erythema was observed at the injection site of the test substance. Following the topical induction, severe erythema and scabs were observed at the test site in 3/10 treated animals. A further 4/10 (in total 7/10) treated and 4/5 control animals exhibited only scabs. No edema was observed (see Table 1). 48 and 72 h after the challenge, no sensitisation was observed in the treated animals. There was no mortality, no signs of toxicity and no treatment-related effects on body weight.

Table 1: skin irritation effects of intradermal and epidermal induction

 

Group/

animal No.

Intradermal induction (Day 3), undiluted test substance

Epidermal induction (Day 10), undiluted test substance

Control

A

B

C

Erythema

Edema

16

E2

NA

E3

0p

0

17

E2

NA

N2

0a

0

18

E3

NA

N3

0a

0

19

E3

NA

N3

0

0

20

E2

NA

N3

0a

0

Experimental

 

 

 

 

 

21

E4

NA

E2

0a

0

22

E1

NA

E1

0

0

23

E2

E2

E2

0a

0

24

E2

NA

E1

0a

0

25

E1

NA

E1

4k

0

26

E1

NA

E1

0

0

27

E3

E1

E2

0a

0

28

E2

E1

E2

4s

0

29

E2

NA

E2

4k

0

30

E3

NA

E2

0

0

A. 1:1 mixture of FCA and water for injection

B. undiluted test substance (experimental group) or vehicle (control group)

C. 1:1 mixture of FCA and undiluted test substance (experimental group) or vehicle (control group)

a. small scabs

k. scabs

p. scaliness

s. eschar formation

 

Skin effect intradermal injections:

NA. No abnormalities

E. erythema

N. signs of necrosis (mm in diameter)

Interpretation of results:
other: not classified based on EU CLP criteria
Conclusions:
Based on the results of the read across study, the constituent 'linear or branched esters' can be considered to be non-sensitising to the skin.
Executive summary:

A study was conducted to determine the skin sensitisation potential of the read across substance, octyldodecyl isooctadecanoate (purity: assumed to be 100%), using guinea pig maximisation test (GPMT), according to OECD Guideline 406 and EU Method B.6, in compliance with GLP. The test was performed in 15 (10 test and 5 control) female albino Himalayan guinea pigs. Based on the preliminary study, undiluted substance (100%) was considered as induction and challenge phase concentration. In the main test, one treated group of ten females received 3 pairs of intradermal injections (0.1 mL/site) [i.e., Injection 1: a 1:1 mixture (w/w) Freud’s Complete Adjuvant (FCA)/water for injection, Injection 2: undiluted test substance, Injection 3: undiluted test substance in a 1:1 mixture (w/w) with FCA (final concentration is 50% test substance)] on Day 1. 48 h after intradermal injection (i.e., on Day 3), the degree of erythema and edema was evaluated. On Day 7, the scapular area between the injection sites was clipped and subsequently rubbed with 10% sodium dodecyl sulfate (SDS) in Vaseline using a spatula. This concentration of SDS provoked a mild inflammatory reaction. On Day 8, 0.5 mL undiluted read across substance was applied to the SDS-treated skin area under semi-occlusive conditions for 48 h. The degree of erythema and edema was evaluated directly after cleaning the skin area with water (Day 10). Similar procedure was followed for control substance (corn oil). For challenge phase, on Day 21, 0.5 mL of undiluted read across substance or control substance was applied to approximately 20 mm x 30 mm, on one flank of the animals and evaluation was made 24 and 48 h after the challenge ended. The animals were observed for mortality twice daily and for signs of toxicity at least once daily. The body weight of the animals was determined on Day 1 (prior to exposure) and at the end of the study period (Day 24). A reliability check was carried out by the lab at regular intervals with alpha-hexylcinnamic aldehyde to check the sensitivity of the test system and the reliability of the experimental methods. 48 h after intradermal induction of the test substance, slight to severe erythema was noted at all of the sites injected with FCA/water and FCA/test substance in 10/10 treated and 5/5 control animals. 4/5 control animals also exhibited necrosis at the FCA/test substance injection site. In 3/10 treated animals slight to well-defined erythema was observed at the injection site of the test substance. Following the topical induction, severe erythema and scabs were observed at the test site in 3/10 treated animals. A further 4/10 (in total 7/10) treated and 4/5 control animals exhibited only scabs. No edema was observed. 48 and 72 h after the challenge, no sensitisation was observed in the treated animals. There was no mortality, no signs of toxicity and no treatment-related effects on body weight. Under the study conditions, the read across substance was determined to be non-sensitiser to the skin (Notox, 1998). Based on the results of the read across study, similar non-sensitising behaviour can be expected for the constituent 'linear or branched esters'.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In absence of short-term toxicity to skin sensitization studies with the test substance, the endpoint has been assessed based on studies for read across substances representative of the main constituents, which can be categorised as phosphate esters (PSE i.e., mono- and di C16 PSE, K+), alcohols (i.e., C16-18 linear and branched alcohol) and esters (i.e., C16-18 linear and branched fatty acid esters). The results are presented below:

Constituent: PSE - read across study:

A study was conducted to determine the skin sensitisation potential of the read across substance, 'Reaction mass of mono- and di- hexadecyl phosphate esters, potassium salts and phosphoric acid' (98.5%) according to OECD Guideline 429 and US EPA OPPTS 870.2600 (LLNA), in compliance with GLP. The read across substance concentrations selected for the main study were based on the results of a pre-screen test. In the main study, four experimental groups of five female CBA/J mice were treated with read across substance concentrations of 2.5, 5, 10 or 25% w/w for three consecutive days, by topical application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone (Liquid petrolatum). A positive control group with a-hexylcinnamaldehyde (HCA - 50%) was also included in the experiment. Five days after the last exposure, all animals were injected with 5-bromo-2'-deoxy-uridine (BrdU) and the draining (auricular) lymph nodes were then isolated and pooled for each animal. Cells were fixed using 70% ethanol and used for the measurement of the cell number and the BrdU determination (percentage of proliferating cells in "S" phase). Flow cytometry was conducted for analysis and stimulation index (SI) was recorded. Mortality/viability, body weights, clinical signs, ear size and irritation (and other local effects) were recorded as well. SI values were similar among the control and test groups and were below 3. Three concentrations (i.e.2.5, 5 and 25%) induced ear swelling. No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period (MBRL, 2005).

Constituent: Alcohol - study on hexadecan-1-ol and read across studies:

Study 1: A study was conducted to determine the skin sensitisation potential of the test substance, 'hexadecan-1-ol', according to the Magnusson & Kligman, 1969 method, using guinea pig maximisation test (GPMT). In induction test, 5% test substance in olive oil, vaseline or ethanol was applied by intracutaneous and occlusive epicutaneous route to the test animals. Challenge test was performed by applying 25% test substance as open patches via epicutaneous route. No evidence of allergic reaction was reportedly observed in any of 20 guinea pigs. Under the study conditions, the test substance was determined to be non-skin sensitiser (Gloxhuber, 1977, OECD SIDS, 2006).

Supporting study on hexadecan-1-ol from OECD SIDS dossier:

A study was conducted to determine the skin sensitisation potential of hexadecan-1-ol (purity:>95%) using GPMT, according to OECD 406, in compliance with GLP. Based on a primary irritation screening study, 1%, 50% and 25-50% test substance solutions in arachis oil were chosen for the intradermal induction, intradermal challenge and topical challenge respectively. A Draize scale was used for erythema and oedema scoring. No sensitisation reactions were observed in any of the test or control animals. Body weights and weight gain over the observation period were comparable in test and control groups. Well defined to moderate erythema was observed at the intradermal injection site 24 h after induction and well-defined erythema at 48 h. Following topical induction very slight to well defined erythema was noted 1 h after patch removal and very slight erythema was observed in 2/10 test animals at 24 h. No skin reactions were observed following topical challenge. No evidence of allergic reaction was reportedly observed in any of 15 guinea pigs. Under the study conditions, the test substance was determined to be non-sensitiser to the skin (OECD SIDS, 2006).

Study 2: A study was conducted to determine the skin sensitisation potential of the read across substance, '1-octanol', using human maximisation test. 25 human volunteers were tested with 2% test substance in petrolatum. No evidence of sensitisation reactions was noted during the study. Under the study conditions, the read across substance was determined to be non-skin sensitiser (Opdyke, 1973).

Study 3: A study was conducted to determine the skin sensitisation potential of the read across substance, 'octadecan-1 -ol', using Official Methods of Analysis of cosmetics and beauty products from Official Journal of the French Republic of 21/4/71, edition Laws and Decrees, and of 5/6/73, edition. Compared to the original guideline, treatment time were reduced from 3 months to 8 weeks and daily readings were expressed as weekly average. The read across substance was suspended in polyoxyethylene sorbitan stearate (3%), preservative (0.2%) and water (to 100%). The read across substance (4 samples) was applied undiluted and as a 10% aqueous dispersion to the skin of rabbits for 60 days. After this, a challenge application was made after a 7-day rest period. No details were provided about negative and positive control substance groups. No data on results were provided other than the statement that 'undiluted test substance application was badly tolerated and 10% test substance application was relatively well tolerated'. Also, it was mentioned that no evidence of allergic reaction was reportedly observed. Under the study conditions, the read across substance was concluded to be non-skin sensitiser (Guillot, 1977).

Further, the presence of branched alcohols in the test substance are not expected to show difference in toxicity compared to the linear alcohols.

Constituent: Ester - read across study to branched ester:

A study was conducted to determine the skin sensitisation potential of the read across substance, octyldodecyl isooctadecanoate (purity: assumed to be 100%), using GPMT, according to OECD Guideline 406 and EU Method B.6, in compliance with GLP. The test was performed in 15 (10 test and 5 control) female albino Himalayan guinea pigs. Based on the preliminary study, undiluted substance (100%) was considered as induction and challenge phase concentration. In the main test, one treated group of ten females received 3 pairs of intradermal injections (0.1 mL/site) [i.e., Injection 1: a 1:1 mixture (w/w) Freud’s Complete Adjuvant (FCA)/water for injection, Injection 2: undiluted test substance, Injection 3: undiluted test substance in a 1:1 mixture (w/w) with FCA (final concentration is 50% test substance)] on Day 1. 48 h after intradermal injection (i.e., on Day 3), the degree of erythema and edema was evaluated. On Day 7, the scapular area between the injection sites was clipped and subsequently rubbed with 10% sodium dodecyl sulfate (SDS) in Vaseline using a spatula. This concentration of SDS provoked a mild inflammatory reaction. On Day 8, 0.5 mL undiluted read across substance was applied to the SDS-treated skin area under semi-occlusive conditions for 48 h. The degree of erythema and edema was evaluated directly after cleaning the skin area with water (Day 10). Similar procedure was followed for control substance (corn oil). For challenge phase, on Day 21, 0.5 mL of undiluted read across substance or control substance was applied to approximately 20 mm x 30 mm, on one flank of the animals and evaluation was made 24 and 48 h after the challenge ended. The animals were observed for mortality twice daily and for signs of toxicity at least once daily. The body weight of the animals was determined on Day 1 (prior to exposure) and at the end of the study period (Day 24). A reliability check was carried out by the lab at regular intervals with alpha-hexylcinnamic aldehyde to check the sensitivity of the test system and the reliability of the experimental methods. 48 h after intradermal induction of the test substance, slight to severe erythema was noted at all of the sites injected with FCA/water and FCA/test substance in 10/10 treated and 5/5 control animals. 4/5 control animals also exhibited necrosis at the FCA/test substance injection site. In 3/10 treated animals slight to well-defined erythema was observed at the injection site of the test substance. Following the topical induction, severe erythema and scabs were observed at the test site in 3/10 treated animals. A further 4/10 (in total 7/10) treated and 4/5 control animals exhibited only scabs. No edema was observed. 48 and 72 h after the challenge, no sensitisation was observed in the treated animals. There was no mortality, no signs of toxicity and no treatment-related effects on body weight. Under the study conditions, the read across substance was determined to be non-sensitiser to the skin (Notox, 1998).

Further, based on the OECD QSAR Toolbox profiling for the linear and branched esters, no difference in toxicity is expected with regard to the skin sensitization endpoint. Therefore, overall based on the available weight of evidence information from studies for substances representative of the main constituents, the test substance is considered to be non-sensitising to skin.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available weight of evidence information from studies for substances representative of the main constituents, the test substance does not warrant a classification for skin sensitisation according to the EU CLP criteria (Regulation 1272/2008/EC).