Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Peer reviewed scientific publication

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1999

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Behavour in standard sensitisation tests were correlated with logP and chemical reactivity rates for four chemicals.
GLP compliance:
no
Type of study:
other: GP Maximization test, Adjuvant & Patch test and Buehler test

Test material

Constituent 1
Reference substance name:
3-(2-dodecenyl)succinic anhydride
EC Number:
243-296-9
EC Name:
3-(2-dodecenyl)succinic anhydride
Cas Number:
19780-11-1
IUPAC Name:
3-dodec-2-en-1-yldihydrofuran-2,5-dione
Test material form:
other: liquid
Details on test material:
2-dodecenyl-1-yl succinic anhydride, purchased from Aldrich Chemical Company, purity stated at 97%.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
not specified
Details on test animals and environmental conditions:
Purchased from Charles River Japan. They were 5-6 weeks old at the start of the test. They were housed as 5 animals per one aluminum cage (Yamato Scientific Co.l, Ltd, 450x550x350 mm) and given free access to filtered tap water and standard diet (GC-4, Oriental Yeast Co., Ltd) throughout the experimental period.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: acetone and corn oil
Concentration / amount:
varous concentrations
Challengeopen allclose all
Route:
other: epicutaneous, wrapped and open
Vehicle:
other: acetone and corn oil
Concentration / amount:
varous concentrations
No. of animals per dose:
5
Details on study design:
The GPMT was carried out as reported previously (Magnusson and Kligman, 1969). The adjuvant and patch test (APT) was carried out as previously reported (Sato, et.al., 1981). The Buehler test (BT) was carried out as previously reported (Buehler, 1965).
The octanol:water partition coefficient (log P) was calculated using a computer system (BioByte software Release 3.55, C-QSAR, Sub system (CLOGP) (Hansch et al., 1995).
Chemical reactivity rates were estimated by the decrease in the amount of 2-phenylethylamine (PEA) in reaction with nDDSA and the positive control compounds. Solutions of 50 mM in DMSO were mixed with 40 mM 2-PEA in DMSO and stirred with a magnetic stirrer for 90 minutes at room temperature. After the reaction, the amount of PEA was measured by HPLC (SUMIPAX ODS column (L-05-4615, 5 µm) 4.6 mm x 15 cm) with a Hitachi L-5200 Intelligent Pump equipped with a Hitachi L-4000 UV detector at 256 nm. The flow rate of eluents (MeOH/H20 = 40:60, v/v, containing 2% PIC B7) through the detector was 1 ml/min. The peak area (A) of PEA reacting with the test compound was divided by the peak area (B) of PEA before the reaction in order to estimate the reactivity rate for each chemical. Reactivity rates = (1-B/A) x 100(%).
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene, maleic anhydride, alpha-hexylcinnamic aldehyde

Results and discussion

Positive control results:
2,4-Dinitrochlorobenzene, maleic anhydride, alpha-hexylcinnamic aldehyde were positive in all three test protocols.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: GPMT challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
1 ppm (0.0001%)
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
at 1 ppm (0.0001%) induction and 1000 ppm (0.1%) challenge
Remarks on result:
other: Reading: other: GPMT challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 1 ppm (0.0001%). No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: at 1 ppm (0.0001%) induction and 1000 ppm (0.1%) challenge.
Reading:
other: APT challenge
Hours after challenge:
72
Group:
test chemical
Dose level:
10 ppm (0.001%)
No. with + reactions:
2
Total no. in group:
5
Clinical observations:
10 ppm (0.001%) induction, 100000 ppm (10%) challenge
Remarks on result:
other: Reading: other: APT challenge. . Hours after challenge: 72.0. Group: test group. Dose level: 10 ppm (0.001%). No with. + reactions: 2.0. Total no. in groups: 5.0. Clinical observations: 10 ppm (0.001%) induction, 100000 ppm (10%) challenge.
Reading:
other: BT challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
1000 ppm (0.1%)
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
1000 ppm (0.1%) induction and 100000 ppm (10%) challenge
Remarks on result:
other: Reading: other: BT challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 1000 ppm (0.1%). No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: 1000 ppm (0.1%) induction and 100000 ppm (10%) challenge.

Any other information on results incl. tables

nDDSA is positive in three sensitization protocols. The minimum induction concentrations were 1 ppm or 0.0001% (GPMT), 10 ppm or 0.001% (APT) and 1000 ppm or 0.1% (BT) as measured at the challenge phase. Minimum rechallenge concentrations of nDDSA were 100 ppm or 0.01% (GMPT and APT) and 1000 ppm or 0.1% (BT).

LogP was estimated through CLOGP QSAR program to be 5.0

Chemical reactivity of nDDSA with 2-phenylethylamine was 100%. Reactivity for maleic anhydride was 100%, for 2,4 -dinitrochlorobenzene was 60% and for alpha-hexylcinnamic aldehyde was 10%.

A chemical category is established for alkenyl succinic anhydrides with C8-C12 alkenyl side chains, based on common functional groups, similar physico-chemical properties, common breakdown/metabolic products via physical and biological processes, and a constant pattern in the changing of the potency across the category.  These include tetrapropenyl succinic anhydride (CAS 26544-38-7), octenyl succinic anhydride (CAS 26680-54-6), n-dodecenyl succinic anhydride (CAS 19780-11-1) and tripropenyl succinic anhydride (CAS 28928-97-4). Common functional groups are a  2,5-Furanedione (cyclic anhydride) ring, a carbon chain of length 8 to 12 carbons (with or without branching methyl groups), and one double bond in the carbon chain, location unspecified (except for n-DDSA where the alkene is C1-C2).  Common breakdown products are the dioic acids of the corresponding anhydride. A constant pattern may also be displayed in acute toxicity, dermal irritancy and biodegradation, with the lowest carbon chain length (C8) displaying the highest irritation potential in vivo and highest biodegradation potential. Irritation and degradation diminishes with increasing carbon chain length. Using the precautionary principle, all category members are classified as dermal sensitisers, so there is no variability in Classification and Labeling, or hazard assessment.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Subcategory 1A applies as 3/5 animals responded when induced with 0.01% in GPMT. Meet criteria of 30% response at ≤ 0.1% induction concentration. Criteria used for interpretation of results: EU
Conclusions:
2-Dodecenyl-1-yl succinic anhydride (nDDSA), a chemical category member with tetrapropenyl succinic anydride (TPSA), was tested in three standard sensitization protocols in guinea pigs, the guinea pig maximization test, adjuvant and patch test and Buehler test. The substance was positive in all three tests. The substance is classified as a dermal sensitizer, category 1A, according to Regulation EC No. 1272, 2008 and Regulation EU No. 286/2011. Therefore, TPSA is also considered a dermal sensitizer, category 1A. Read-across with the category is adequate to fulfill the information requirements, to be the basis for classification and labelling decisions, and for risk assessment.