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EC number: 203-576-3 | CAS number: 108-38-3
- 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: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP status not known, data fromguideline studies, published in peer reviewed literature,no restrictions, fully adequate for assessment (although very limited data on evaluation of xylene in the LLNA included.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- GLP compliance:
- not specified
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- not specified
- Sex:
- not specified
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 100%
- Details on study design:
- The assay was conducted using the standard protocol that contains the essential elements of the Guideline. Stimulation indices (SI) were derived by comparing cell proliferation in auricular lymph nodes from treated animals (quantified using thymidine incorporation) with that of the vehicle control group. The criterion for a positive response in the LLNA is that a SI of 3 or more is induced by one or more application concentrations of the test substance compared with the concurrent control group.
- Parameter:
- SI
- Remarks on result:
- other: SI = 3.1. This result indicates a very slightly positive result at the highest concentration tested 100%.
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: No data
- Interpretation of results:
- not sensitising
- Conclusions:
- Xylene is not a skin sensitiser.
- Executive summary:
The sensitisation potential of mixed xylenes when tested in the LLNA was described by Basketter et al. (1996), who reported an SI = 3.1 following topical treatment of mice with neat (100%) substance. However while this finding is suggestive of a slightly positive result, it appears to be a false positive given the absence of structural alerts present in the substance, the very weak response obtained (recorded only at the very highest concentration tested), and the absence of any corroborative information from clinical experience, or from other human studies (Basketter and Kimber, 2010) A subsequent statistical analysis of LLNA data for 134 chemicals (including mixed xylenes) performed by Basketter et al. (1999) concluded that a SI “cut-off” value of 3.5 would lead to greater specificity in the interpretation of LLNA results, and also reduce the occurrence of occasional false positive results such as that reported for mixed xylenes (Basketter and Kimber, 2010).
Reference
Basketter et al. (1996) discussed the merits and methodology behind the LLNA assay, and presented tabulated results for a wide range of substances including mixed xylenes.
Basketter et al. (1999) conducted a statistical analysis (using Receiver Operating Characteristic curves) of data for 134 chemicals tested in the LLNA and in the guinea pig, or for which human information was available, to determine the specificity and sensitivity of the test.
Basketter and Kimber (2010) performed a weight of evidence evaluation of the sensitisation potential of mixed xylenes which included their own LLNA findings together with other chemical and biological considerations.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Non-Human Information
There is no relevant non-human information for the individual isomers.
The sensitisation potential of mixed xylenes when tested in the standard local lymph node assay was reported by Basketter et al. (1996), who obtained a stimulation index of 3.1 following topical treatment of mice with neat (100%) substance. However while this finding is suggestive of sensitisation (according to the strict interpretative criteria of the Guideline), it appears to be a false positive given the absence of structural alerts present, the very weak response obtained (recorded only at the very highest concentration tested), and a lack of any corroborative information from clinical experience, or from other human studies (discussed Basketter and Kimber, 2010). A subsequent statistical analysis of LLNA data for 134 chemicals (including mixed xylenes) performed by Basketter et al. (1999) concluded that a SI “cut-off” value of 3.5 would lead to greater specificity in the interpretation of LLNA results, and also reduce the occurrence of occasional false positive results such as the SI = 3.1 for undiluted mixed xylenes (Basketter and Kimber, 2010). Overall it is concluded that this publication does not provide convincing evidence that mixed xylenes possess a potential to induce or elicit skin sensitisation.
The sensitisation potential of mixed xylenes was also assessed in a modified local lymph node assay where increased ear-draining lymph node weight and cell counts were used to quantify lymph node cell proliferation by 9 laboratories participating in a ring-trial. [3H]TdR incorporation in vitro by lymph node cells was also assessed in a single laboratory (assay not conducted by other laboratories). Acute skin inflammation (a potential confounder that can lead to "false positive" results) was also determined based on changes in ear tissue weight. Treatment with mixed xylenes was associated with a statistically significant increase in ear-draining lymph node weight and cell count in 7 of the 9 laboratories, and an increase in ear tissue weight in 3 of 9 laboratories. An increased (but not quantified) increase in 3[H]TdR incorporation by lymph node cells was also reported by one laboratory. Based on these findings, mixed xylene was considered an allergen by a majority of laboratories participating in the trial. However the methodology used was evaluated by an ECVAM Workshop (reported by Basketter et al., 2008) which concluded the assay methods deviated from the Guideline in terms of the strain of mouse, the choice of vehicle, the time of lymph node/lymph node cell collection, and the magnitude of the SI used to differentiate positive and negative samples. Overall, the ECVAM Workshop concluded that these differences represented a major change in methodology that required further validation. The use of [3H]TdR incorporation by lymph node cells in vitro (as opposed to incorporation of [3H]TdR following i.v. injection in vivo, as required by the Guideline) was not discussed by the ECVAM Workshop but is another change relative to the Guideline. When conducting a weight of evidence evaluation of the sensitisation potential of mixed xylenes, Basketter and Kimber (2010) also noted that these deviations meant that deviations meant that the findings were of limited toxicological relevance. Overall it is concluded that this publication does not provide convincing evidence that mixed xylenes possesses a potential to induce or elicit skin sensitisation.
Human information
From widespread use, there have been no reports of skin sensitising properties of xylene isomers (including mixed xylenes) as a result of skin contact. In a human maximization test (Kligman, 1966), mixed xylenes was tested at 100% and subjects were challenged at 25%. No skin sensitization resulted. This test is considered to be a highly sensitive detector of skin sensitizing potential; the results for more than 80 chemicals were presented in the publication which demonstrates the very considerable predictive sensitivity of this assay.
Conclusion
Mixed xylenes gave a marginal (SI = 3.1) response in a standard LLNA at the highest concentration tested (100%; Basketter et al., 1996) however an absence of chemical structural alerts, the very weak response obtained, and a lack of any corroborative human information indicates that this is a false positive (Basketter and Kimber, 2010). Results suggestive of a positive response obtained from a non-standard LLNA are considered unreliable given the extent of the methodological deviations present (Basketter et al., 2008; Basketter and Kimber, 2010). Results from a human maximisation test on mixed xylenes (Kligman, 1966) using an induction concentration of 100% were negative. Overall there is no convincing evidence that mixed xylenes possess a potential to induce or elicit skin sensitisation. Xylene gave a very slightly positive result in the LLNA when tested undiluted, but the result fits well with the criteria for a false positive. It is an unreactive chemical that would not be identified on the basis of chemical structure as being a potential skin sensitizer. Added to which is the clinical evidence demonstrating that xylene does not cause skin sensitization in humans, even when tested in a very rigorous human predictive assay. Thus, the evidence is that xylene isomers should not be classified as having a potential to cause skin sensitization.
Short description of key information:
A human maximization test, a sensitive detector of the skin sensitising properties of chemicals, found that xylene did not induce skin sensitisation. The individual xylene isomers are not considered to be skin sensitizers.
Justification for selection of skin sensitisation endpoint:
Mixed xylenes gave a marginal (SI = 3.1) response in a standard LLNA at the highest concentration tested (100%; Basketter et al., 1996) however an absence of chemical structural alerts, the very weak response obtained, and a lack of any corroborative human information indicates that this is a false positive (Basketter and Kimber, 2010). Results suggestive of a positive response obtained from a non-standard LLNA are considered unreliable given the extent of the methodological deviations present (Basketter et al., 2008; Basketter and Kimber, 2010). Results from a human maximisation test on mixed xylenes (Kligman, 1966) using an induction concentration of 100% were negative. Overall there is no convincing evidence that mixed xylenes possess a potential to induce or elicit skin sensitisation.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Additional information:
Short description of key information:
No data available, but no evidence of respiratory sensitisation reported from worker exposure to xylene isomers.
Justification for classification or non-classification
Xylene isomers (including mixed xylenes) are unreactive chemicals that would not be identified on the basis of chemical structure as being potential skin sensitizers. In addition, there is no clinical evidence demonstrating that xylenes cause skin sensitization in humans, even when tested in a very rigorous human predictive assay. Therefore, xylene isomers (including mixed xylenes) do not warrant classification as having a potential to cause skin sensitisation under CLP.
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