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EC number: 905-287-4 | CAS number: 1638758-52-7
- 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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7.05 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 12.34 mg/m³
- Most sensitive endpoint:
- acute toxicity
DNEL related information
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- NOAEC
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.75 mg/kg bw/day
- Most sensitive endpoint:
- acute toxicity
DNEL related information
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- NOAEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - workers
Acute toxicity - systemic
Available dose-descriptors per endpoint as a result of hazard assessment |
||||
Endpoint |
Quantitative dose-descriptor |
Associated Effect |
Remarks on Study |
|
Systemic Effect |
||||
Acute toxicity |
Oral |
NOAEL 175 mg/kg |
Reduced food consumption |
Rat |
Derm. |
No data |
- |
- |
|
Inhal. |
No data |
- |
- |
Dose descriptor selection
The lowest, reliable NOAEL observed was selected from an acute rat oral study on mixed xylenols. A further study on mixed ethyl phenols returned the same NOAEL value. The available data for all three cresol isomers was already provided (therefore reports were not available to enable complete evaluation and suitability for the LD50 / LOAEL values set). These studies are in excess of 40 years old and consequently not conducted to any guideline, with data absent. The LOAEL determined have been dictated by the dose levels set, with clinical signs of toxicity observed at the LOAEL similar to that observed at higher doses in both the guideline compliant studies on ethylphenols and xylenols. Comparable signs of toxicity were reported compared to the xylenols and ethyl phenols, furthermore, based on structural similarities, if these studies were performed to modern guideline requirements it is reasonable to assume that comparable NOAEL would be obtained.
Assessment of mode of action
The identified endpoint of and the observed effects have a threshold.
Acute Dermal - systemic
Dose description modification
Guidance [1. Appendix R8-1] was followed for route to route extrapolation as no relevant dose descriptor were available for dermal exposure. As noted in [1.] R.8.4.2, as no information regarding dermal absorption is available, a worse case scenario that 100% of the dose will be absorbed dermally has been assumed.
NOAELcorr = NOAEL / Allometric scaling*(ABS oral rat / ABS derm rat) * (ABS derm rat / ABS derm human)
NOAELcorr (general) = 175mg/kg bw / 4 * (50% (default) / 100% (default)) * (100% (default) / 100% (default)) = 21.88 mg/kg bw
Assessment factors
Default assessment factors [1. R-8.4.3.3.] were applied.
Assessment factor = Interspecies * Intraspecies (worker) * Exposure duration * Dose-response * Quality of whole database
Assessment factor (general) = 2.5 * 5 * 1 * 1 * 1 = 12.5
DNEL derivation
DNEL = NOAELcorr / Assessment factor
DNEL = 21.88 mg/kg bw/day / 12.5 = 1.75 mg/kg bw/day
Acute Inhalation - systemic
Dose description modification
Guidance [1. Appendix R8 -1] was followed for route to route extrapolation as no relevant dose descriptor were available for inhalation exposure. As noted in R.8.4.2, as no information regarding inhalation absorption is available, a worse case scenario that 100% of the dose will be absorbed via the inhalation route. The dose descriptor was modified to take into account an 8 hour exposure and the respiratory volume corrected for light work.
NOAECcorr = NOAEL *1 / rat resp. volume * oral / inhalation absorption * human resting resp. volume / worker resp. volume
NOAECcorr(general) = 175 mg/kg/bw *(1 / 0.38) * (50% (default) / 100%(default)) * 6.7 m3 (8hr) / 10 m3 (8hr) = 154.28 mg/m3
Assessment factors
Default assessment factors [1. R-8.4.3.3.] were applied.
Assessment factor = Interspecies * Intraspecies * Exposure duration * Dose-response * Quality of whole database
Assessment factor (general) = 2.5 * 5 * 1 * 1 * 1 = 12.5
DNEL derivation
DNEL = NOAELcorr / Assessment factor
DNEL = 154.28 mg/m3/ 12.5 = 12.34 mg/m3
Endpoint Specific DNELs for Workers |
||||
Endpoint |
Corrected dose-descriptor |
Overall AF |
Endpoint Specific DNEL |
|
Systemic |
|
Systemic |
||
Acute toxicity |
Oral |
N/A |
|
N/A |
Derm. |
21.88 mg/kg |
12.5 |
1.75 mg/kg |
|
Inhal. |
154.28 mg/m3 |
12.5 |
12.34 mg/m3 |
Acute / repeat– dermal, local
Cresols and xylenols are classified under Directive 67/548/EEC as irritant/corrosive. Available animal studies show concordance with this classification. As such, a qualitative approach [[1]. R.8.5.3. Page 51-53]] has been taken, with the mixture considered to be corrosive when in contact with skin.
Acute / repeat– inhalation, local
None of the components of the mixture are classified for endpoints relating to short term inhalation toxicity, local effects. However cresols are reported to cause local irritation to nose and throat when inhaled [2] and therefore it is reasonable to assume that both xylenols and ethyl phenols are expected to cause a similar effect. As such, a qualitative approach has been taken, with the mixture considered to be irritant when inhaled.
Long term exposure
The sub acute repeat oral 28 day study conducted on ethyl phenols and xylenols confirms a NOAEL at 100 mg/kg/day for both test materials, where as sub-chronic and chronic studies on cresol isomers all report similar findings, with NOAEL values which were not only comparable between isomers but also not appreciably different from the NOAEL derived from a 28 day study, irrespective of whether the test material was administered via the diet or orally via gavage.
In respect of the reproductive data available on cresols, for all three isomers the NOAEL for both maternal and developmental toxicity in the rat exceeds 100 mg/kg bw so use of this value as the overall NOAEL is conservative. However, for all three isomers the NOAEL for maternal toxicity in the rabbit is 5 mg/kg bw and the parental NOAEL in the multigeneration study is 30 mg/kg bw. In addition the NOAEL for developmental toxicity in the rabbit was 50 mg/kg bw for o-cresol.
Reports of the studies which established these NOAELs are not available to JSC and only summaries can be used to assess whether these NOAELs are robust. These show that the NOAEL for maternal toxicity in the rabbit is based mainly on clinical signs such as audible respiration, hypoactivity and ocular discharge in rabbits receiving 50 mg/kg bw of all three isomers. There may have been some mortality (incidence not reported) in rabbits given 50 mg/kg bw p-cresol but the summary of mortality data for this study is ambiguous and, as no mortality was reported with either of the other two isomers, even if there was a death at 50 mg/kg bw it was probably not treatment related. As the clinical signs of toxicity were not particularly adverse and there was no evidence of developmental effects at any dose level of any isomer, 50 mg/kg bw can be considered a NOEL and the NOAEL in all three developmental toxicity studies of the cresol isomers should be ≥100 mg/kg bw.
The parental NOAEL in the multi generation study of all three isomers is based on observations of perioral wetness at 175 mg/kg. There was also a possible increase in still births at this dose level but there was no clear dose response suggesting that it was not treatment related. As the clinical signs of toxicity were mild and there was a considerable spacing between the LOAEL (30 mg/kg bw) and the NOAEL (175 mg/kg bw) it is likely that the true NOAEL for this study is approximately 100 mg/kg bw which is the overall NOAEL for xylenols.
o-Cresol is only a very small component of the xylenols and its presence is consequently unlikely to affect the NOAEL for any xylenol, the NOAEL of 50 mg/kg bw for developmental toxicity in the rabbit can therefore be ignored.
Cresols constitute <25% of xylenols and so would only affect NOAELs of mixtures in which they were present if they were significantly more toxic than xylenol isomers. Although the reports of reproductive and developmental toxicity studies of cresol isomers are not available, the data discussed above show they are probably of comparable toxicity to xylenol isomers so NOAELs for xylenols can be used to derive DNEL for xylenols containing cresols. This is also to be expected based on the similarity of the structures.
Therefore, the oral sub-acute study has been used to derive dermal and inhalation DNEL. As the duration of the study does not appreciably alter the NOAEL, there is no need to take into account an additional assessment factor for duration extrapolation [[1.] pg 35]].
Available dose-descriptors per endpoint as a result of hazard assessment |
||||
Endpoint |
Quantitative dose-descriptor |
Associated Effect |
Remarks on Study |
|
Systemic Effect |
||||
Repeat toxicity (sub-acute) |
Oral |
NOAEL 100 mg/kg |
Adverse clinical observations (urine-stained fur, increased kidney, liver and ovarian relative weight). |
Rat |
Derm. |
No data |
- |
- |
|
Inhal. |
No data |
- |
- |
Long term exposure –dermal systemic
Guidance [1. Appendix R8-1] was followed for route to route extrapolation as no relevant dose descriptor was available for dermal exposure. As noted in R.8.4.2, as no information regarding dermal absorption is available, a worse case scenario that 100% of the dose will be absorbed dermally has been assumed.
NOAELcorr = NOAEL/Allometric scaling*(ABS oral rat / ABS derm rat) * (ABS derm rat / ABS derm human)
NOAELcorr (general) = 100mg/kg bw/4 * (50% (default) / 100% (default)) * (100% (default) / 100% (default)) = 12.5 mg/kg bw
Assessment factors
Default assessment factors [1. R-8.4.3.3.] were applied.
Assessment factor = Interspecies * Intraspecies * Exposure duration * Dose-response * Quality of whole database
Assessment factor (general) = 2.5 * 5 * 1 * 1 * 1 = 12.5
DNEL derivation
DNEL = NOAELcorr / Assessment factor
DNEL = 12.5 mg/kg bw/day / 12.5 = 1.00 mg/kg bw/day
Long term exposure – inhalation systemic
Dose description modification
Guidance [1. Appendix R8-1] was followed for route to route extrapolation as no relevant dose descriptor were available for inhalation exposure. As noted in R.8.4.2, as no information regarding inhalation absorption is available, a worse case scenario that 100% of the dose will be absorbed via the inhalation route. The dose descriptor was modified to take into account an 8 hour exposure and the respiratory volume corrected for light work.
NOAECcorr = NOAEL *1 / rat resp. volume * oral / inhalation absorption * human resting resp. volume / worker resp. volume
NOAECcorr(general) = 100 mg/kg/bw *(1 / 0.38) * (50% (default) / 100%(default)) * 6.7 m3 (8hr) / 10 m3 (8hr) = 88.16 mg/m3
Assessment factors
Default assessment factors [1. R-8.4.3.3.] were applied.
Assessment factor = Interspecies * Intraspecies * Exposure duration * Dose-response * Quality of whole database
Assessment factor (general) = 2.5 * 5 * 1 * 1 * 1 = 12.5
DNEL derivation
DNEL = NOAELcorr / Assessment factor
DNEL = 88.16 mg/kg bw/day / 12.5 = 7.05 mg/kg bw/day
Endpoint Specific DNELs for Workers |
||||
Endpoint |
Corrected dose-descriptor |
Overall AF |
Endpoint Specific DNEL |
|
Systemic |
Systemic |
|||
Repeat toxicity |
Oral |
N/A |
N/A |
N/A |
Derm. |
12.5 mg/kg |
12.5 |
1.00 mg/kg |
|
Inhal. |
88.16 mg/m3 |
12.5 |
7.05 mg/m3 |
References:
1. ECHA, (May, 2008). Guidance on information requirements and chemical safety assessment. Chapter, R.8. – Dose [concentration]-response regarding human health.
2. New
Jersey Department of Health and Senior Services. Cresols (mixed isomers)
hazardous substance fact
sheet.http://nj.gov/health/eoh/rtkweb/documents/fs/0537.pdf
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - General Population
No exposure to general population, therefore no requirement to establish DNEL for the general population.
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