resorcinol; 1,3-benzenediol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.6 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEL

Value:

80 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

140 mg/m³

Explanation for the modification of the dose descriptor starting point:

A 14 -day range finding study (Industrial Health Foundation Inc., 1977) is the only available inhalation study. This study is considered inadequate for assessing endpoints such as histopathological examination. Therefore, the NOAEL from the key oral study (CIT, 2004) was used for DNEL derivation, with route-to-route extrapolation based on default values from the ECHA guidance, and assuming 8 hour/day worker exposure.

AF for dose response relationship:

1

Justification:

Best professional judgment and ECHA default for NOAEL-based DNEL calculation. Presumes minimal or no uncertainty in the oral NOAEL. Criteria met in regards to dose spacing, shape and slope of dose-response curve, extent/severity of effect at LOAEL, quality of study (=1, valid without restriction).

AF for differences in duration of exposure:

2

Justification:

ECHA default for subchronic to chronic extrapolation.

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA default. Allometrric scaling is not required when using the oral NOAEL to estimate an inhalation DNEL.

AF for other interspecies differences:

2.5

Justification:

ECHA default.

AF for intraspecies differences:

5

Justification:

ECHA default.

AF for the quality of the whole database:

1

Justification:

Best professional judgement. Although the inhalation data base is limited to a single 14-day range finding study with one test concentration in rats, the oral database is of good/standard quality.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

132.8 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

5

Dose descriptor:

NOAEC

Value:

664 mg/m³

AF for dose response relationship:

1

Justification:

The DNEL derivation is based on a NOAEC.

AF for differences in duration of exposure:

1

Justification:

ECHA default

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA default

AF for other interspecies differences:

1

Justification:

ECHA default

AF for intraspecies differences:

5

Justification:

ECHA default

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

40 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):

100

Dose descriptor starting point:

NOAEL

Value:

80 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

4 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No dermal repeat-dose study available. Therefore, the NOAEL from the key oral study (CIT, 2004) was used for DNEL derivation, with route-to-route extrapolation based on default values from the ECHA guidance, and assuming 8 hour/day worker exposure.

AF for dose response relationship:

1

Justification:

Best professional judgment and ECHA default for NOAEL-based DNEL calculation. Presumes minimal or no uncertainty in the oral NOAEL. Criteria met in regards to dose spacing, shape and slope of dose-response curve, extent/severity of effect at LOAEL, quality of study (=1, valid without restriction).

AF for differences in duration of exposure:

2

Justification:

ECHA default for subchronic to chronic extrapolation.

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA default.

AF for other interspecies differences:

2.5

Justification:

ECHA default.

AF for intraspecies differences:

5

Justification:

ECHA default.

AF for the quality of the whole database:

1

Justification:

Best professional judgment. Although no repeated dose dermal studies were identified, the oral data base is of a good/standard quality.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

repeated dose toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

Based on available data, the most relevant reproducible effect, body weight changes, was identified as the basis for establishing the DNEL. This value is more conservative than those identified in association with local and/or acute effects. As such, and in accordance with ECHA Guidance Document R.8, Characterization of Dose[Concentration]-Response for Human Health dated May 2008, DNELs for several of the above identified population groups and effects were not performed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.39 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEL

Value:

80 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

69 mg/m³

Explanation for the modification of the dose descriptor starting point:

Only one inhalation study available. In this study, only one concentration was used, with a small number of animals and no histopathological examination. The 90-day inhalation study is considered invalid as it does not meet the requirements of current guidelines. Therefore, the NOAEL from the key oral study (CIT, 2004) was used for DNEL derivation, with route-to-route extrapolation based on default values from the ECHA guidance, and assuming 24 hour/day exposure.

AF for dose response relationship:

1

Justification:

Best professional judgment and ECHA default for NOAEL-based DNEL calculation. Presumes minimal or no uncertainty in the oral NOAEL. Criteria met in regards to dose spacing, shape and slope of dose-response curve, extent/severity of effect at LOAEL, quality of study (=1, valid without restriction).

AF for differences in duration of exposure:

2

Justification:

ECHA default for subchronic to chronic extrapolation.

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA default. Allometrric scaling is not required when using the oral NOAEL to estimate an inhalation DNEL.

AF for other interspecies differences:

2.5

Justification:

ECHA default.

AF for intraspecies differences:

10

Justification:

ECHA default.

AF for the quality of the whole database:

1

Justification:

Best professional judgement. Although the inhalation data base is limited to a single 14-day range finding study with one test concentration in rats, the oral database is of good/standard quality.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

33 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

Dose descriptor:

NOAEC

Value:

330 mg/m³

AF for dose response relationship:

1

Justification:

The DNEL derivation is based on a NOAEC.

AF for differences in duration of exposure:

1

Justification:

ECHA default

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA default

AF for other interspecies differences:

1

Justification:

ECHA default

AF for intraspecies differences:

10

Justification:

ECHA default

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20 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):

200

Dose descriptor starting point:

NOAEL

Value:

80 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

4 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No dermal repeat-dose study available. Therefore, the NOAEL from the key oral study (CIT, 2004) was used for DNEL derivation, with route-to-route extrapolation based on default values from the ECHA guidance, and assuming 24 hour/day exposure.

AF for dose response relationship:

1

Justification:

Best professional judgment and ECHA default for NOAEL-based DNEL calculation. Presumes minimal or no uncertainty in the oral NOAEL. Criteria met in regards to dose spacing, shape and slope of dose-response curve, extent/severity of effect at LOAEL, quality of study (=1, valid without restriction).

AF for differences in duration of exposure:

2

Justification:

ECHA default for subchronic to chronic extrapolation.

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA default.

AF for other interspecies differences:

2.5

Justification:

ECHA default.

AF for intraspecies differences:

10

Justification:

ECHA default.

AF for the quality of the whole database:

1

Justification:

Best professional judgment. Although no repeated dose dermal studies were identified, the oral data base is of a good/standard quality.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

repeated dose toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.4 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):

200

Dose descriptor starting point:

NOAEL

Value:

80 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

80 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Best professional judgment and ECHA default for NOAEL‐based DNEL calculation. Presumes minimal or no uncertainty in the oral NOAEL. Criteria met in regards to dose spacing, shape and slope of dose‐response curve, extent/severity of effect at LOAEL, quality of study (=1, valid without restriction).

AF for differences in duration of exposure:

2

Justification:

ECHA default for subchronic to chronic extrapolation.

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA default.

AF for other interspecies differences:

2.5

Justification:

ECHA default.

AF for intraspecies differences:

10

Justification:

ECHA default.

AF for the quality of the whole database:

1

Justification:

Best professional judgment and ECHA default. Presumes a good/standard quality oral data base.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - General Population

Based on available data, the most relevant reproducible effect, body weight changes, was identified as the basis for establishing the DNEL. This value is more conservative than those identified in association with local and/or acute effects. As such, and in accordance with ECHA Guidance Document R.8, Characterization of Dose[Concentration]-Response for Human Health dated May 2008, DNELs for several of the above identified population groups and effects were not performed.