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EC number: 209-400-1 | CAS number: 576-26-1
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Modified dose descriptor starting point:
- NOAEC
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- Justification:
- default value - subacute to chronic
- AF for other interspecies differences:
- 2.5
- Justification:
- default value - remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- default value - workers
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 6 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor:
- NOAEC
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- Justification:
- default value - subacute to chronic
- AF for other interspecies differences:
- 2.5
- Justification:
- default value - remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- default value - workers
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 16 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- Overall assessment factor (AF):
- 12.5
- Dose descriptor starting point:
- NOAEC
- AF for dose response relationship:
- 1
- AF for other interspecies differences:
- 2.5
- Justification:
- default value - remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- default value - workers
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.2 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 300
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 60 mg/kg bw/day
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- Justification:
- default value - subacute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default value - rat
- AF for other interspecies differences:
- 2.5
- Justification:
- default value - remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- default value - workers
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.6 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - workers
Based on the physico-chemical parameters, it could be concluded that absorption will be 100% for all routes of exposure (more details can be found in the part on toxicokinetics).
DNEL for long-term exposure - systemic effects – inhalation :
Batelle Columbus Division (BCD) (1991) performed a repeated dose toxicity study in male and female rats that were exposed to 2,6-xylenol (67, 200, 670 mg/m³) by whole body inhalation for 6 hours/day, 5 days/week, for a total of ten exposures, conducted within 14 days. The NOAEC for local and systemic effects was determined to be 200 mg/m³.
To compensate for the difference in exposure duration, the inhalation NOAEC is multiplied by a factor 6h/day/8h/day and is 150 mg/m³.
Following assessment factors were used:
-interspecies differences: 2.5 (no allometric scaling is required for inhalation)
-intraspecies differences: 5
-differences in duration: 6
-dose-response relationship: 1
With an overall assessment factor of 75, a DNEL of 150 mg/m³/75 = 2 mg/m³ is derived for the inhalation route – long-term systemic effects.
DNEL for acute exposure - systemic effects – inhalation :
The substance is classified for acute oral toxicity therefore, to protect from any possible adverse acute systemic effect, a DNEL for acute exposure inhalation has been set at 3x the long-term systemic DNEL.
DNEL for long-term exposure - local effects – inhalation:
Batelle Columbus Division (BCD) (1991) performed a repeated dose toxicity study in male and female rats that were treated with 2,6-xylenol (67, 200, 670 mg/m³) by whole body inhalation for 6 hours/day, 5 days/week, for a total of ten exposures, conducted within 14 days. The NOAEC for local effects was determined to be 200 mg/m³.
To compensate for the difference in exposure duration, the inhalation NOAEC is multiplied by a factor 6h/day/8h/day and is 150 mg/m³.
Following assessment factors were used:
-interspecies differences: 2.5
-intraspecies differences: 5
-differences in duration: 6
-dose-response relationship: 1
With an overall assessment factor of 75, a DNEL of 150 mg/m³/75 = 2 mg/m³ is derived for the inhalation route – local effects.
DNEL for acute exposure - local effects – inhalation :
Batelle Columbus Division (BCD) (1991) performed a repeated dose toxicity study in male and female rats that were treated with 2,6-xylenol (67, 200, 670 mg/m³) by whole body inhalation for 6 hours/day, 5 days/week, for a total of ten exposures, conducted within 14 days. Local effects appeared after 1 day of exposure: the NOAEC for local effects was determined to be 200 mg/m³.
Although the study is a repeated dose study, effects were observed after the first day of exposure. Therefore, 200 mg/m³ can be used as the starting dose for the acute DNEL derivation.
Following assessment factors were used:
-interspecies differences: 2.5
-intraspecies differences: 5
-differences in duration: 1
-dose-response relationship: 1
With an overall assessment factor of 12.5, an acute DNEL of 200 mg/m³/12.5 = 16 mg/m³ is derived for the inhalation route – local effects.
DNEL for long-term exposure - systemic effects – dermal :
No long-term data were available for the dermal route of exposure. Therefore, reliable data for the oral route were used.
RTI International Center for Life Sciences (2005) performed a combined repeated dose toxicity study with reproduction/developmental toxicity screening test using a structurally related analogous. F0 Sprague-Dawley Rats were dosed (via gavage) premating through the day prior to necropsy. Recovery males, females and 28 days females were dosed for 28 days. F1 animals were dosed post-weaning until the day before scheduled necropsy, at least 7 weeks duration. Animals received 0, 10, 100, or 200 mg/kg bw/day. A parental and F0 offspring NOEL of >= 200 mg/kg bw/day was observed. In addition to this study, a pre-natal developmental toxicity study was conducted with the registered substance where female rats received 0, 60, 180 or 540 mg/kg bw/day from gestation day 6 to 15. A lowest NOAEL for maternal toxicity (systemic toxicity) was obtained in this study because treatment at 180 mg/kg bw/day caused reductions in body weight gain and food consumption, and a statistically significant lower terminal weight when corrected for the uterus weight. Therefore, the starting dose for DNEL derivation is the NOAEL of 60 mg/kg bw/day for maternal toxicity, the lowest NOAEL obtained among the available studies.
Following assessment factors were used:
- interspecies differences: 2.5 x 4 = 10
- intraspecies differences: 5
- differences in duration: 6
- dose-response relationship: 1
With an overall assessment factor of 300, a DNEL for long-term exposure - systemic effects of 60 mg/kg bw/300 = 0.2 mg/kg bw/day is derived.
DNEL for acute exposure - systemic effects – dermal :
The substance is classified for acute dermal toxicity therefore, to protect from any possible adverse acute systemic effect, a DNEL for acute exposure dermal has been set at 3x the long-term systemic DNEL.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
For the general population, no DNEL was derived since 2,6-xylenol is only used in closed systems: no indirect exposure via the environment will occur. Moreover, no consumer use is considered.
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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