Cinnamonitrile

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Justification for type of information:

Data is from peer reviewed journals

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Correlation between experimental human and murine skin sensitization induction thresholds

Author:

Anne Marie Api, David Basketter, and Jon Lalko

Year:

2015

Bibliographic source:

Cutaneous and ocular toxicology, 34, no. 4, (2015), 298-302.

Reference 2

Reference Type:

publication

Title:

Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients

Author:

Anne Marie Api , David A. Basketter ,, Peter A. Cadby , Marie-France Cano , Graham Ellis, G. Frank Gerberick , Peter Griem , Pauline M. McNamee , Cindy A. Ryan , Robert Safford

Year:

2008

Bibliographic source:

Regulatory Toxicology and Pharmacology 52 (2008) 3–23

Reference 3

Reference Type:

publication

Title:

Skin sensitization in chemical risk assessment: Report of a WHO/IPCS international workshop focusing on dose–response assessment

Author:

Henk van Loveren , Amanda Cockshott , Tom Gebel , Ursula Gundert-Remy

Year:

2008

Bibliographic source:

Regulatory Toxicology and Pharmacology 50 (2008) 155–199

Reference 4

Reference Type:

secondary source

Title:

Opinion on fragrance allergens in cosmetic products

Author:

Scientific Committee on Consumer Safety

Year:

2012

Bibliographic source:

Scientific Committee on Consumer Safety adopted this opinion at its 15th plenary meeting 2012.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Principles of method if other than guideline:

To evaluate the skin sensitization potential of Cinnamonitrile by Mouse Local Lymph Node Assay

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Cinnamonitrile

EC Number:

217-552-5

EC Name:

Cinnamonitrile

Cas Number:

1885-38-7

Molecular formula:

C9H7N

IUPAC Name:

cinnamonitrile

Details on test material:

IUPAC: Cinnamonitrile
CAS No:1885-38-7
EC No: 217-552-5
Commen name: Cinnamyl Nitrile
Molecular formula : C9H7N
Molecular weight : 129.161 g/mol
substance type: organic
InChI: 1S/C9H7N/c10-8-4-7-9-5-2-1-3-6-9/h1-7H/b7-4+
Smiles :N#C\C=C\c1ccccc1
physical state: colourless to yellow liquid

Specific details on test material used for the study:

IUPAC: Cinnamonitrile
CAS No:1885-38-7
EC No: 217-552-5
Commen name: Cinnamyl Nitrile
Molecular formula : C9H7N
Molecular weight : 129.161 g/mol
substance type: organic
InChI: 1S/C9H7N/c10-8-4-7-9-5-2-1-3-6-9/h1-7H/b7-4+
Smiles :N#C\C=C\c1ccccc1
Physical state: colorless- yellow liquid

In vivo test system

Study design: in vivo (LLNA)

Vehicle:

other: 1:3 ethanol :diethyl phthalate.

Concentration:

25 µl (Each group received one of five test concentrations prepared as a w/v%.)

No. of animals per dose:

Total=5

Details on study design:

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: EC 3 value
TREATMENT PREPARATION AND ADMINISTRATION: Groups of female CBA/CA mice were dosed topically on the dorsum of each ear with 25 µl of test fragrance in 1:3 ethanol: diethyl phthalate.

Each group received one of five test concentrations prepared
as a w/v%.

Positive control substance(s):

other: Concurrent vehicle control used- 1:3 ethanol:diethyl phthalate

Results and discussion

In vivo (LLNA)

Results

Key result

Parameter:

EC3

Value:

> 2 500

Remarks on result:

other: skin sensitizing

Cellular proliferation data / Observations:

The stimulation index (SI) values were calculated for each dose level. An SI of 3 or more was considered to give a positive response.

Applicant's summary and conclusion

Interpretation of results:

other: Skin sensitizing

Conclusions:

The EC3 value obtained from LLNA assay performed to assess the sensitizing potential of cinnamyl nitrile was > 2500 microgram/sq cm. Based on this value, cinnamyl nitrile can be considered to be sensitizing to skin.

Executive summary:

Skin sensitization potential of Cinnamonitrile was evaluated by Local Lymph Node Assay (LLNA) The LLNAs were conducted according to the method described inOECD Guideline 429. Groups of female CBA/CA mice (n= 5) were dosed topically on the dorsum of each ear with 25 ml of test material in 1:3 ethanol :diethyl phthalate. Each group received one of five test concentrations prepared as a w/v%. A concurrent vehicle control group was similarly treated with 1:3 ethanol: diethyl phthalate. Dosing occurred daily for three consecutive days. The animals received no treatment for two days and on the sixth day after the first application, all mice were injected intravenously via the tail vein with 250 ml of phosphate buffered saline containing 20 µCi of radiolabelled methyl thymidine (3HTdR). Five hours later, the mice were euthanized and the draining auricular lymph nodes were excised and pooled . Suspensions of the lymph node cells were prepared by mechanical disaggregation through 200-mesh stainless steel gauze. The cell suspensions were washed three times with phosphate buffered saline and precipitatedovernight at 4 °C with 5% w/v trichloroacetic acid (TCA). The samples were then pelleted by centrifugation. The cells were resuspended in 1ml of TCA and transferred to scintillation vials containing 10 ml of scintillation fluid. The incorporation of 3HTdR was measured by β- scintillationcounting and expressed as disintegrations per minute (dpm) per lymph node.

No description of the effects observed during the study and observation phase have been reported.

The EC3 value obtained from LLNA assay performed to assess the sensitizing potential of cinnamyl nitrile was > 2500 microgram/sq cm. Based on this value, cinnamyl nitrile can be considered to be sensitizing to skin.