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Diss Factsheets
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EC number: - | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation
- Remarks:
- other: QSAR
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Assessment made with accepted QSAR model (TOXTREE)
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- The mechanism of toxicity for most skin sensitizers is by covalent bond formation with skin proteins. It is accepted that for a chemical to have skin sensitizing potential it must either be directly electrophilic or have the potential to be converted (via oxidation or metabolism) into an electrophile These reactions can be described in terms of nucleophilic-electrophilic reaction chemistry. Therefore, a QSAR analysis may be made via assesment of a chemical's potential mechanism of action which enables prediction of the substances nucleophilic-electrophilic reaction chemistry.
- GLP compliance:
- no
- Type of study:
- other: Expert report based on QSAR model
- Species:
- other: The QSAR model
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: expert judgment
- Conclusions:
- Evaluation of alkylated naphthalene with the TOXTREE model for skin sensitization alerts indicates the substance has no structural alerts for sensitization. The weight of the available evidence indicates the substance is not sensitizing.
- Executive summary:
The sensitization potential of Alkylated Naphthalene was made using the QSAR model in the TOXTREE set of models. In order to reduce both the cost and the numbers of animals tested for skin sensitization determination, the use of quantitative structure-activity relationships (QSAR) has been encouraged and should be part of compliance testing strategies.
The mechanism of toxicity for most skin sensitizers is by covalent bond formation with skin proteins. It is accepted that for a chemical to have skin sensitizing potential it must either be directly electrophilic or have the potential to be converted (via oxidation or metabolism) into an electrophile [1]. These reactions can be described in terms of nucleophilic-electrophilic reaction chemistry. Therefore, the initial step in QSAR analysis is the assessment of a chemical's potential mechanism of action which enables placement of the substance in an appropriate reactivity domain.
A recently published dataset of 210 LLNA test results was used as the primary training data in order to derive the SMARTS patterns for the five mechanisms of action. The goal of Enoch et al. [2] was to create a series of SMARTS patterns capable of reproducing the expert classification recently published by Roberts et al. [3]. The SMARTS strings developed covered a number of possible reactions within each of the five electrophilic mechanisms. In addition, a range of likely oxidation and metabolism transformations were included. The SMARTS patterns correctly identified the mechanisms of action of 203 of the 208 chemicals investigated. In the majority of cases (195) only a single mechanism of action was assigned to each chemical, however for the remaining 13 chemicals two potential mechanisms were identified.
Having defined the initial SMARTS patterns, a second recently published series of 44 LLNA assay results with mechanisms of action assigned to them was used to validate the rules [4]. The mechanisms assigned by the SMARTS patterns were in agreement with those assigned by Roberts et al. [4] for 40 out of the 44 chemicals. In six cases more than a single possible mechanism was suggested, with three chemicals being assigned to the SN2 and acylation mechanisms and two chemicals flagging both the SN2 and Michael addition mechanisms.
Evaluation of alkylated naphthalene with the TOXTREE model for skin sensitization alerts indicates the substance has no structural alerts for sensitization. If a chemical fails to trigger any of the electrophilic rules coded in the SMARTS patterns, it does not necessarily mean that it will be a non-sensitizer. It should be recognized that animal-based studies do not identify all sensitizers also. Final evaluations should be based on a weight of evidence approach. For Alkylated Naphthalene it is significant, therefore, that no reports of sensitization reactions have been reported for the substance or its commercial product formulation.
Based on the modeling results and the history of use of the product, it is concluded that alkylated naphthalene poses acceptably low or negligible risks of sensitization effects and does not require classification.
References
[1] A.O. Aptula, G. Patlewicz, and D.W. Roberts, Skin sensitization: Reaction mechanistic applicability domains for structure–activity relationships, Chem. Res. Toxicol. 18 (2005), pp. 1420–1426.
[2]Enoch SJ,Madden JC,Cronin.2008. Identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach.SAR QSAR Environ Research.19(5-6): 555-78.
[3] D.W. Roberts, G. Patlewicz, P.S. Kern, F. Gerberick, I. Kimber, R.J. Dearman, C.A. Ryan, D.A. Basketter, and A.O. Aptula, Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitization, Chem. Res. Toxicol. 20 (2007),
pp. 1019–1030.
[4] D.W. Roberts, G. Patlewicz, S.D. Dimitrov, L.K. Low, A.O. Aptula, P.S. Kern,
G.D. Dimitrova, M.I.H. Comber, R.D. Phillips, J. Niemela, C. Madsen, E.B. Wedebye,
P.T. Bailey, and O.G. Mekenyan, A mechanistic evaluation of an external
validation study using reaction chemistry principles, Chem. Res. Toxicol. 20 (2007),
pp. 1321–1330.
Reference
The representative constituent of alkylated naphthalene was entered into the TOXNET program using the SMILES code for the substance.
The program made the following SMARTS evaluations for this structure (SMARTS are 2D structural descriptors) :
Nucleophilic Aromatic Substitution |
No |
Schiff Base Formation |
No |
Michael Acceptor |
No |
Acyl Transfer Agents |
No |
Nucleophilic Aliphatic Substitution |
No |
At least one alert for skin sensitisation? |
No |
Classification No skin sensitization alerts identified.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Evaluation of Alkylated Naphthalene with the TOXTREE model for skin sensitization alerts indicates the substance has no structural alerts for sensitization. The weight of the available evidence indicates the substance is not sensitizing.
Migrated from Short description of key information:
The TOXTREE model for skin sensitization alerts indicates the substance has no structural alerts for sensitization.
The history of use of the product indicates no incidences of human sensitization.
Justification for selection of skin sensitisation endpoint:
The sensitization potential of Alkylated Naphthalene was made using the QSAR model in the TOXTREE set of models. In order to reduce both the cost and the numbers of animals tested for skin sensitization determination, the use of quantitative structure-activity relationships (QSAR) has been encouraged and should be part of compliance testing strategies.
Justification for classification or non-classification
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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