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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.45 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
261.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral NOAEL / [sRV * time] *ABS(oral)/ABS(inhal) * no/light work = 300 mg/kg bw/d / [0.8 L/min/kg bw rat * 8*60 min] * 50%/100% * 6.7m3/10m3 = 300 /0.384 *1/2 *0.67 mg/m3
AF for dose response relationship:
1
Justification:
NOAEL of a GLP, OECD408 study with 3 doses
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
see route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default for worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
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
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral NOAEL * 1/1 *ABS(oral)/ABS(derm) = 300 mg/kg bw/d *1 *100%/50% = 300 *1 *2 mg/kg bw/d
AF for dose response relationship:
1
Justification:
NOAEL of a GLP, OECD408 study with 3 doses
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Extrapolation systemic effects rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Acute exposure - systemic effects

It is not necessary to derive a DNEL for acute effects based on the available data. In an acute oral study (BASF AG, 1974) the LD50 (rat) was 8000 mg/kg bw, but this route is not relevant for workers. There is no relevant risk to be expected from inhalative exposure since the inhalation hazard toxicity test (BASF 1974) showed no effects. This is supported by the read across to texanol (CAS 1115-77-4) and NPG (CAS 126-30-7). No systemic effect is also expected via the dermal route, as the LD50 for the read across substance texanol (CAS 25265 -77-4) was above 15200 mg/kg bw in rabbits.

Acute exposure - local effects

HPN is classified as "Risk of serious damage to eyes" (R41). A test was performed (as the guideline prescribes) with undiluted test substance. Therefore, this test does not provide dose-response data that could be used for the derivation of a DNEL.

It is not possible to derive a DNEL based on the available data. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent eye exposure.

Long-term exposure - systemic effects

The DNELs for inhalation and dermal long term exposure are derived from the subchronic oral NOAEL, which was obtained from an OECD 408 study (BASF SE, 2013). At 1000 mg/kg bw/day transient, treatment-related adverse findings were observed: head shaking, unsteady gate, semiclosed or closed eyes, poor general condition, adominal position, twitching, atonia splayed limbs, labored and intermitted respiration; therefore the NOAEL is 300 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.61 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
130.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral NOAEL / [sRV * time] *ABS(oral)/ABS(inhal) = 300 mg/kg bw/d / [0.8 L/min/kg bw rat * 24*60 min] * 50%/100% = 300 /1.15 /2 mg/m3
AF for dose response relationship:
1
Justification:
NOAEL of a GLP, OECD408 study with 3 doses
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No interspecies extrapolation for inhalation, see route to route
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
DNEL (Derived No Effect Level)
Value:
3 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral NOAEL * 1/1 *ABS(oral)/ABS(derm) = 300 mg/kg bw/d *1 *100%/50% = 300 *1 *2 mg/kg bw/d
AF for dose response relationship:
1
Justification:
NOAEL of a GLP, OECD408 study with 3 doses
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no extrapolation
AF for dose response relationship:
1
Justification:
NOAEL of a GLP, OECD408 study with 3 doses
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default general population
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:
15.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
LOAEL
DNEL value:
4 640 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no extrapolation
AF for dose response relationship:
3
Justification:
LOAEL to NOAEL.
AF for interspecies differences (allometric scaling):
4
Justification:
rat to huma
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Acute exposure - systemic effects

Inhalation and dermal exposure: same considerations as for the worker. An oral short-term DNEL may be considered. This DNEL is derived from an acute oral toxicity study comparable to OECD 401 (BASF, 1974). Five male and five female rats were gavaged with 35% aqueous solutions at dose levels of 4640 and 10000 mg/kg bw. The LOAEL was 4640 mg/kg bw, as one female but no male animal died.

Acute exposure - local effects

Same considerations as for the worker.

Long term exposure - systemic effects

The DNELs for inhalation and dermal long term exposure are derived from the subchronic oral NOAEL, which was obtained from a OECD 408 study (BASF SE; 2013). At 1000 mg/kg bw/day transient, treatment-related adverse findings were observed: head shaking, unsteady gate, semiclosed or closed eyes, poor general condition, abdominal position, twitching, atonia splayed limbs, labored and intermitted respiration; therefore the NOAEL is 300 mg/kg bw/day.