Registration Dossier

Administrative data

Description of key information

TERPINOLENE MONOCONSTITUENT, one of the main constituent of the registered substance, is classifed as skin senitiser 1B. Therefore, according to the rules of classification criteria of Regulation (EC) No 1272/2008 (CLP), REACTION MASS OF 2,2,6-TRIMETHYL-1-OXASPIRO[2.5]OCT-5-ENE AND 4-ISOPROPYLIDENE-1-METHYLCYCLOHEXENE is classified as skin sensitiser 1B.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
TERPINOLENE MONOCONSTITUENT (source substance) is one of the main constituents of the registered substance (target substance).
Reason / purpose for cross-reference:
read-across source
Positive control results:
The threshold positive value of 3 for the SI was reached in the positive control group (SI = 8.94). The experiment was therefore considered valid.
Parameter:
SI
Remarks on result:
other: see table 7.4.1/1
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see table 7.4.1/1

Table 7.4.1/1: Results of skin sensitization

Treatment and concentrations

No. of nodes per group

dpm per group

dpm per node

Stimulation index (SI)

Increase in ear thickness (% between Day 1 and Day 6)

Irritation level

EC3 value

Vehicle

8

2706

338.25

-

-1.03

-

-

2.5 %

8

3347

418.38

1.24

-1.00

I

8 %

5 %

8

5781

722.63

2.14

5.15

I

10 %

8

9290

1161.25

3.43

2.04

I

25 %

8

39074

4884.25

14.44

1.01

I

50 %

8

55509

6938.63

20.51

10.00

II

α-hexylcinnamaldehyde

8

24195

3024.38

8.94

-

-

-

                            

dpm = disintegrations per minute

I = non-irritant (increase in ear thickness < 10 %)

II = slightly irritant (increase in ear thickness = 10 to 25 %)

EC3 value = theoretical concentration resulting in a SI value of 3

stimulation index = dpm of treated group / dpm of control group

 

 

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A dose-related increase in the SI was recorded at concentrations ≥ 2.5%, and the threshold positive value of 3 was exceeded at the concentration of 10%. In the absence of local irritation, the significant lymphoproliferative responses observed were attributed to delayed contact hypersensitivity.
Therefore, terpinolene monoconstituent is classified as sensitising "R43: May cause sensitisation by skin contact" according to Directive 67/548/EEC and skin sensitiser Category 1B according to CLP Regulation (EC) No 1272/2008.
Executive summary:

In a local lymph node assay performed according to OECD guideline No 429 and in compliance with GLP, terpinolene monoconstituent in Acetone/Olive oil (4/1, v/v) was administered to CBA/J 9 weeks old mice.

In a preliminary study, dryness of the skin and/or eryhema was observed on days 3 and/or 6 in ears of 2 animals treated at 50% or 100%. A notable increase in ear thickness was recorded at the concentration of 100%, showing the irritant potential of the test item at this concentration, therefore the highest concentration retained for the main test was 50%.

In a main study, five treated groups of four animals received applications of 25 μL of terpinolene monoconstituent to the external surface of both ears at the concentrations of 2.5, 5, 10, 25, and 50% for 3 consecutive days.

The positive control used was α-hexylcinnamaldehyde which presented a stimulation index of 8.94. Therefore, the positive control gave acceptable positive results and the study can be considered as valid.

No clinical signs and no mortality were observed during the main test. No local reactions and no notable increase in ear thickness were observed at any of the concentrations. Stimulation index for 2.5, 5, 10, 25, and 50 % were 1.24, 2.14, 3.43, 14.44 and 20.51, respectively. The calculated effective concentration inducing a SI of 3 (EC3) was 8%.

A dose-related increase in the SI was recorded at concentrations ≥ 2.5%, and the threshold positive value of 3 was exceeded at the concentration of 10%. In the absence of local irritation, the significant lymphoproliferative responses observed were attributed to delayed contact hypersensitivity.

Therefore, terpinolene monoconstituent is classified as sensitising "R43: May cause sensitisation by skin contact" according to Directive 67/548/EEC and skin sensitiser Category 1B according to CLP Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Data were available from scientific litterature about the sensitisation of TERPINOLENE MONOCONSTITUENT, one of the main contituents of the registered substance.

In a LLNA performed according to OECD 429 Guideline and in compliance with GLP, groups of CBA/J mice (4 females/dose) were exposed to 25 µL

of terpinolene monoconstituent in Acetone/Olive oil (4/1, v/v) at concentrations of 0 (vehicle control), 2.5, 5, 10, 25 and 50 % (v/v) to the dorsal surface of both ears for three consecutive days.

No clinical signs and no mortality were observed during the main test. No local reactions and no notable increase in ear thickness were observed at any of the tested concentrations. Stimulation Index for 2.5, 5, 10, 25, and 50 % were 1.24, 2.14, 3.43, 14.44 and 20.51, respectively. The calculated effective concentration inducing a SI of 3 (EC3) was 8 %. A dose-related increase in the SI was recorded at concentrations higher than 2.5%, and the threshold positive value of 3 was exceeded at the concentration of 10%. In the absence of local irritation, the significant lymphoproliferative responses observed were attributed to delayed contact hypersensitivity. Therefore, terpinolene monoconstituent was considered as skin sensitising.

REACTION MASS OF 2,2,6-TRIMETHYL-1-OXASPIRO[2.5]OCT-5-ENE AND 4-ISOPROPYLIDENE-1-METHYLCYCLOHEXENE is classified as skin sensitiser 1B.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Data were available from scientific litterature about the sensitisation of TERPINOLENE MONOCONSTITUENT, one of the main contituents of the registered substance.

TERPINOLENE MONOCONSTITUENT one of the main constituent of the registered substance, is classifed as skin senitiser 1B because

positive response was indiced in a LLNA with an EC3 = 8%.

Therefore, according to the rules of classification criteria of Regulation (EC) No 1272/2008 (CLP), REACTION MASS OF 2,2,6-TRIMETHYL-1-OXASPIRO[2.5]OCT-5-ENE AND 4-ISOPROPYLIDENE-1-METHYLCYCLOHEXENE is classified as skin sensitiser 1B.