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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
98 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 091 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see discussion below and attached documentation to this record
Overall assessment factor (AF):
9
Modified dose descriptor starting point:
LOAEC
Value:
9 824 mg/m³
Explanation for the modification of the dose descriptor starting point:

An acute inhalation DNEL needs to be derived as the substance is classified for acute toxicity by the inhalation route. No suitable data is available, therefore a value for the systemic route therefore a value is derived by route to route extrapolation from the a LOAEL is based on the data from human poisoning incidents by the oral route. Of those values reported, the lowest estimated dose was 400mg/kg, which produced adverse but reversible symptoms. Route to route extrapolation can then be performed as shown:

Assume 5m3 inhaled over 4hrs exposure - half of normal workday exposure estimate of 10m3 over 8hrs, table R.8 -2, 57% absorption efficiency, 70kg worker = 9824mg/m3. (=400x70/5/0.57) (Inhalation absorption efficiency based on work of Johansson, 1986 - see chapter 7.1.1) Note that the theoretical inhalation figure used as the starting poin is above the saturated vapour concentration.

AF for dose response relationship:
3
Justification:
LOAEL to NOAEL extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
not required, human data
AF for other interspecies differences:
1
Justification:
not required, human data
AF for intraspecies differences:
3
Justification:
See document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
246 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
Dermal
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:
DNEL (Derived No Effect Level)
Value:
59 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
426 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: see discussion below and attached documentation to this record
Overall assessment factor (AF):
15
Modified dose descriptor starting point:
LOAEC
Value:
12 760 mg/m³
Explanation for the modification of the dose descriptor starting point:

An acute inhalation DNEL needs to be derived as the substance is classified for acute toxicity by the inhalation route. No suitable data is available, therefore a value for the systemic route therefore a value is derived by route to route extrapolation from the a LOAEL is based on the data from human poisoning incidents by the oral route. Of those values reported, the lowest estimated dose was 400mg/kg, which produced adverse but reversible symptoms. Route to route extrapolation can then be performed as shown:

 Assume 3.33m3 inhaled over 4hrs exposure - one sixth of consumer exposure estimate of 20m3 over 24hrs, table R-8.2, 57% absorption efficiency, 60kg consumer = 12760mg/m3. (=400x60/3.3/0.57) (Inhalation absorption efficiency based on work of Johansson, 1986 - see chapter 7.1.1) Note that this starting point is well in excess of the saturated vapour concentration.

AF for dose response relationship:
3
Justification:
LOAEL->NOAEL
AF for interspecies differences (allometric scaling):
1
Justification:
not required, human data
AF for other interspecies differences:
1
Justification:
not required, human data
AF for intraspecies differences:
5
Justification:
See attached document
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
147 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: see discussion below and attached documentation to this record
Overall assessment factor (AF):
10.9
Modified dose descriptor starting point:
LOAEL
Value:
69 mg/kg bw/day
AF for dose response relationship:
3
Justification:
LOAEL to NOAEL. There is evidence to suggest that the NOAEL is only a little less than the LOAEL
AF for differences in duration of exposure:
1
Justification:
No factor is used for study length as the data shows that the severity of effect does not increase from 90 days to lifetime exposure.
AF for interspecies differences (allometric scaling):
7.2
Justification:
For the oral route, the LOAEL (69mg/kg from the NTP key repeat dose oral study in mice - see chapter 7.5.1) is equivalent to a human dose of 9.5mg/kg (based on extrapolation using the PBPK model - see chapter 7.1.1 of IUCLID). This accounts for toxicokinetic effects. This is converted into an allometric scaling factor of 7.25
AF for other interspecies differences:
0.1
Justification:
based on lower sensitivity of humans to key effect of haemolysis. See IUCLID chapter 7.9.3.
AF for intraspecies differences:
5
Justification:
See document attached to this record
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26.7 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see discussion below and attached documentation to this record
Overall assessment factor (AF):
15
Modified dose descriptor starting point:
LOAEL
Value:
400 mg/kg bw/day
AF for dose response relationship:
3
Justification:
LOAEL to NOAEL
AF for interspecies differences (allometric scaling):
1
Justification:
not required, human data
AF for other interspecies differences:
1
Justification:
not required, human data
AF for intraspecies differences:
5
Justification:
See document attached to this record
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

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