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Description of key information

A maximization test was carried out on 25 volunteers.Methyl abietate was tested at a 2% concentration in petrolatum and produced no sensitization reaction. Therefore Methyl abietate (127-25-3) was considered to be not sensitizing in human

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from secondary source
Qualifier:
equivalent or similar to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
To assess the sensitizing potential of Methyl abietate using the Maximization assay
GLP compliance:
not specified
Type of study:
other: Human Maximization test
Justification for non-LLNA method:
No data available
Specific details on test material used for the study:
- Name of the test material: Methyl abietate
- IUPAC name: methyl (1R,4aR,4bR,10aR)-1,4a-dimethyl-7-(propan-2-yl)-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carboxylate
- Molecular formula: C21H32O2
- Molecular weight: 316.4818 g/mol
- Substance type: Organic
- Smiles: COC(=O)[C@]1(C)CCC[C@]2(C)[C@H]3CCC(=CC3=CC[C@@H]12)C(C)C
Species:
other: Human
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data available
Route:
other: No data available
Vehicle:
petrolatum
Concentration / amount:
2%
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
2%
No. of animals per dose:
25
Details on study design:
No data available
Challenge controls:
No data available
Positive control substance(s):
not specified
Statistics:
No data available
Positive control results:
No data available
Reading:
1st reading
Group:
test chemical
Dose level:
2%
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
No skin sensitization reaction was observed
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: Not sensitizing
Conclusions:
A maximization test was carried out on 25 volunteers.Methyl abietate was tested at a 2% concentration in petrolatum and produced no sensitization reaction. Therefore Methyl abietate (127-25-3) was considered to be not sensitizing in human
Executive summary:

A maximization test was carried out on 25 volunteers.Methyl abietate was tested at a 2% concentration in petrolatum and produced no sensitization reaction. Therefore Methyl abietate (127-25-3) was considered to be not sensitizing in human.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Skin sensitization

In different studies, Methyl abietate (127-25-3) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in human and guinea pig for target chemical, Methyl abietate (127-25-3) and its structurally similar read across substancesglyceryl rosinate(8050-31-5)andBis(2-ethylhexyl)adipate (DEHA)(103-23-1). the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across

The experimental study conducted by D.L.J. Opdyke (Food and Cosmetics Toxicology, Volume 12, Issues 7–8, December 1974, Page 931)A maximization test was carried out on 25 volunteers. Methyl abietate was tested at a 2% concentration in petrolatum and produced no sensitization reaction. Therefore Methyl abietate (127-25-3) was considered to be not sensitizing in human.

The skin sensitization potential of Methyl abietate (127-25-3) was estimated by SSS (2017) using OECD QSAR toolbox v 3.3 with log kow as the primary descriptor and considering the six closest read across substances Methyl abietate(127-25-3)was predicted to be not sensitizing to the skin of female CBA/CaCrl mouse.

Prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be negative on guinea pig and human for Methyl abietate Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for Methyl abietate (127-25-3) estimated to be not sensitizing when applied to human and guinea pig skin.

The experimental study conducted byM. Hausen, A. Krueger, J. Mohnert, H. Hahn and A.Konig(Contact Dermatitis1989: 20: 41-50). Sensitization was carried out by a method containing modifications of the FCA-method and the guinea pig maximization test (GPMT) on Female Albino guinea pigs of the Pirbright white strain, weight 280-350 g, were kept 3 to a cage, at a constant temperature of 22-24°C, a relative humidity of 50-55%, under artificial illumination for 10 h a day, and nourished with Altrornin® and water ad libitum. Readings were performed every day at the same time under the same lighting conditions. 10 animals were used for each substance. The compound was pulverize in a mortar with a pestle and stirred with a magnetic stirrer after the addition of 4 ml of Freund's complete adjuvant until the material became completely dissolved. Then, 4 ml physiological saline was added and an emulsion was prepared by mixing these 2 solvents in a 5 ml syringe until emulsification was complete. Intradermal injections of 6 x 0.1- 0.15 ml of this emulsion, containing 30 mg of test compound, were made in a semicircular arc on the clipped and shaved shoulder area (4 x 6 cm) from left to right, in such a way that the whole quantity of the emulsion was exhausted for the 10 animals (including common losses).This procedure was repeated on the 5th and 9th days, leaving a gap of 2-3 cm between the rows of injection.

In challenge phase, 11 days after induction, open epicutaneous elicitation was performed by applying 0.05 ml of subirritant doses of the compounds to the clipped and shaved right flank of the treated animals. The reactions were read at 24, 48 and 72 h. The mean responses were computed as the quotient of the sum of all reactions obtained divided by the total number of treated animals. Methyl abietate was considered to be a moderate sensitizer.

Also it is further Supported by experimental study conducted byMonice M. Fiume, Bart A. Heldreth(Int J Toxicology. 2004; 23, Suppl 2:55-94.) to evaluate the skin sensitizing potential of read across substanceglyceryl rosinate(8050-31-5)in human.The Maximization assay was conducted to evaluate the sensitization potential of blush containing 2% glyceryl rosinate.27 healthy adult volunteers aged from 18 – 56 years old (11 male and 16 female) were tested. Contact allergy was not observed in any of the subjects during either of the two grading periods (all scores = 0).It was concluded that blush containing 2% glyceryl rosinate(8050-31-5) did not possess a detectable contact sensitizing potential and hence it is considered not skin sensitizing in human.

Also it is further supported by experimental study conducted byOECD SIDS(SIDS Initial Assessment Report for SIAM 10, page no 51, 2000) to evaluate the skin sensitizing potential of read across substanceBis(2-ethylhexyl)adipate (DEHA)(103-23-1). A guinea pig maximization test was carried out on 10 male guinea pig. Bis(2-ethylhexyl)adipate (DEHA)(103-23-1)was tested at a 0.1 %concentration in olive oil. In induction phase intradermal injection given 3times per week for 3 weeks .After 2 weeks rest period challenge dose given. After 24hr of challenge dose evolution was carried out. The average area and height of the reaction at challenge were smaller than during induction was observed. Hence Bis(2-ethylhexyl)adipate (DEHA)(103-23-1) was considered to be not sensitizing in male guinea pig.

 

Thus based on the above predictions onMethyl abietate (127-25-3) as well as its read across and applying weight of evidence, it can be concluded that Methyl abietate (127-25-3) is not a skin sensitizer. Thus comparing the above studies with the criteria of CLP regulation, Methyl abietate (127-25-3) can be considered as not classified for skin sensitization.

 

 

 

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, Methyl abietate (127-25-3) can be considered as not classified for skin sensitization.