Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.975 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):
30
Dose descriptor starting point:
NOAEL
Value:
237 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
208.93 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 500 mg/kg bw/day established in the combined 28-day repeated dose toxicity study/reproductive toxicity screening study (oral route, OECD 422; Griffiths, 2018) translates into a dose of 237 mg/kg bw/day of THEMAH (purity 47.3%) and was used to derive a DNEL long-term, systemic effects via the inhalation route. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point NOAEC is 208.93 mg/m³ = 237 mg/kg bw/day x 1/0.38 m³/kg/day x 0.67 x 0.5. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure for workers). For workers, the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under respective conditions (6.7 m³ for base level, 10 m³ for light activity).

A correction factor of 0.5 is applied as bioavailability after oral exposure is assumed to be 50% and the bioavailability after inhalation exposure is assumed to be 100%.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point; no additional assessment factor required
AF for differences in duration of exposure:
6
Justification:
difference in study duration, subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
included in the route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
default assessment factor, local effects
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.975 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):
120
Dose descriptor starting point:
NOAEL
Value:
237 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
237 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term dermal toxicity study is available for the test substance. However, data from an oral combined repeated dose toxicity study with reproduction/developmental toxicity screening study (OECD 422; Griffiths, 2018) could be used after extrapolation to the dermal route. The NOAEL was established at 500 mg/kg bw/d, which translates in a dose of 237 mg/kg bw/d (purity 47.3%). For route-to-route extrapolation from oral to dermal, no default factor (i.e. factor 1) should be applied as part of the overall assessment factor, as it is assumed that dermal absorption will not be higher than oral absorption (50%).

AF for dose response relationship:
1
Justification:
NOAEL was used as starting point; no additional assessment factor required
AF for differences in duration of exposure:
6
Justification:
difference in study duration subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
1
Justification:
default assessment factor, local effects
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

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 consumer use is expected, therefore no hazard assessment for the general population is performed.