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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
Not sensitising by structural similarity to acetyl tributyl citrate
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Remarks:
- Predates Commission Regulation (EU) 2016/1688
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Justification for type of information:
- An analogue approach is used for the hazard assessment of several human health endpoints. The hypothesis for the analogue approach is that data can be read-across from data-rich substances, namely acetyl tributyl citrate (ATBC, CAS 77-90-7), acetyl triethyl citrate (CAS 77-89-4) and triethyl citrate (TEC, CAS 77-93-0) to acetyl trihexyl citrate (ATHC, CAS 24817-92-3). The analogue approach is based on common breakdown products via physical and biological processes, and similar functional groups, according to Annex XI, Section 1.5, of Regulation EC No. 1907/2006. Read-across to ATHC is indicated in order to avoid unnecessary in vivo testing according to Article 25 of Regulation EC No. 1907/2006.
The analogue approach to evaluating the safety of triethyl citrate is adopted here, reflecting the approach used by various expert panels and authoritative bodies in their safety assessment of TEC, included JECFA, EFSA, U.S. FDA, EPA and CIR. The use of analogues for hazard evaluation is justified (Scenarios 1 and 2 of the RAAF, 2015) because the substances have common breakdown products via physical and biological processes, which reflects the similar functional groups in their chemical structure. The proposed analogues have similar functional groups, including: a citric acid (tricarboxylic acid) backbone, three short-chain alkyl esters, and an acetyl group (except for TEC). Other than the acetyl group, there are no other functional groups which may introduce additional toxicities. The substances display similar classification based on similar toxicities.
The target substance is expected to have essentially the same effect in the toxicity test/endpoint as does the source substance. Dose descriptors obtained for derivation of a DNEL are adequate and appropriate, and do not underestimate the hazards of the registered substance.
This information is adequate to fulfill the data requirements of Annex IX, to be the basis for classification and labelling decisions, and for risk assessment. - Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Principles of method if other than guideline:
- predates establishment of OECD 406 guideline
- GLP compliance:
- not specified
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The in vivo study was commissioned prior to the passage of Commission Regulation (EU) 2016/1688 amending Regulation (EC) No. 1907/2006 on these testing obligations.
- Species:
- guinea pig
- Route:
- intradermal and epicutaneous
- Vehicle:
- other: 0.01% Dobs/saline
- Concentration / amount:
- Induction: 2.5% in 0.01% Dobs/saline.
Induction-dermal: (occlusive patch application) with 100%.
Challenge (covered patch application) with 50% in absolute ethanol - Day(s)/duration:
- 21
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: ethanol
- Concentration / amount:
- Induction: 2.5% in 0.01% Dobs/saline.
Induction-dermal: (occlusive patch application) with 100%.
Challenge (covered patch application) with 50% in absolute ethanol - Day(s)/duration:
- 21
- Adequacy of challenge:
- highest non-irritant concentration
- No.:
- #2
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: ethanol
- Concentration / amount:
- 50%
- Day(s)/duration:
- 7
- Adequacy of challenge:
- highest non-irritant concentration
- No.:
- #3
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: ethanol
- Concentration / amount:
- 50%
- Day(s)/duration:
- 7
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- 10 (one dose group)
- Details on study design:
- Ten guinea pigs according to the Magnusson-Kligman guinea pig maximization test method. Sensitization was induced by intradermal injections of both test substance and Freunds Adjuvant and the induction process supplemented seven days later by the test substance applied to the shoulder injection sites (2 in x 2 in) under occlusion (adhesive plaster, Poroplast, wound around trunk). The animals were challenged by occluded patch 14 days later. Second and third challenges were made in a weekly interval.
- Challenge controls:
- negative controls: 4 vehicle treated and 4 non-treated
- Positive control substance(s):
- no
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 2
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 3
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Remarks:
- One animal killed in extremis
- Key result
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50% induction
- No. with + reactions:
- 2
- Total no. in group:
- 9
- Remarks on result:
- no indication of skin sensitisation
- Remarks:
- same results at 48 h
- Key result
- Reading:
- other: Rechallenge #2
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 2
- Total no. in group:
- 9
- Remarks on result:
- no indication of skin sensitisation
- Remarks:
- all resolved at 48 h
- Interpretation of results:
- GHS criteria not met
- Remarks:
- GHS
- Conclusions:
- The test substance, ATBC, showed no evidence of sensitisation in guinea pigs, under the conditions of a guideline Magnusson Kligman Maximisation Test. Two rechallenges were undertaken on the test animals in order to verify the absence of sensitisation. This data is appropriate for read-across to the larger ester,acetyl trihexyl citrate, rather than data from smaller esters, TEC or ATEC.
Reference
Animal 2 was killed in extremis due to an ulcerated neck application site. The positive reactions were mild and no more extreme than reactions in vehicle and/or untreated controls. Essentially none was considered a true positive.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
ATBC was non-sensitising in a GPMT. In the same experiment under the same conditions, smaller esters were postitive (triethyl citrate, acetyl triethyl citrate). It is likely that larger esters are likely less bioavailable, resulting in less risk for sensitisation.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
A thorough in vivo study on dermal sensitisation was performed on a series of alkyl citrate esters. The smaller chain esters were sensitisers, but the larger acetyl tributyl citrate was clearly not sensitising in three dermal challenges of the substance. The most appropriate read-across analogue for ATHC is the larger ester, ATBC, which is less likely bioavailable via the dermal route. It is considered non-sensitising and is not classified according to Regulation EC No. 1272/2008.
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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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