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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.78 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
Value:
144.58 mg/m³
Explanation for the modification of the dose descriptor starting point:
82 mg/kg/day x (1/0.38 x 6.7/10) - No correction for inhalatory and oral absorption rates. The vapour pressure is small (0.00287 Pa at 20°C), therefore MOTE has a low volatility
AF for dose response relationship:
1
Justification:
use of a NOAEL as dose descriptor and the low toxicity of the test substance
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
good quality of the whole database
AF for remaining uncertainties:
2.5
Justification:
remaining differences
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:
82 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
Value:
8 200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
82 mg/kg/day x (100/1)
AF for dose response relationship:
1
Justification:
use of a NOAEL as dose descriptor and the low toxicity of the test substance
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat
AF for other interspecies differences:
1
Justification:
no difference in dermal absorption between rats and human as worst-case assumption (rat skin is generally more permeable than human skin)
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
good quality of the whole database
AF for remaining uncertainties:
2.5
Justification:
remaining differences
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

For acute effects, no significant effects that would justify systemic DNEL derivation were observed in the corresponding acute toxicity studies. For local effects, the substance was only slightly irritating to the rabbit skin, with mean values not triggering classification and with no data on dose-response available, and not-irritating to the rabbit eye.

Occupational exposure to MOTE may occur by inhalation or dermal route. For long-term systemic effects, DNEL derivation was performed following the method proposed in the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8.

In a previously conducted OECD TG 421 study (Waalkens-Berendsen, 2009 - Reproduction/Developmental Toxicity Sceening Test), evidence was already obtained that possible effects on thymus weights from repeated exposure to MOTE of pregnant/lactating females were not accompanied by any microscopic findings. As the OECD TG 408 study (Lina, 2014 - Repeated Dose 90-Day Oral Toxicity in Rodents), performed at the same dose levels, lasts considerably longer and includes many more toxicological endpoint, this study has been considered the more appropriate and the key study for systemic long-term DNELs derivation.

For the inhalation long-term systemic DNEL, no correction for inhalatory and oral absorption rates was applied. The vapour pressure is very low (0.00287 Pa at 20°C), therefore MOTE has a low volatility and would not be available for inhalation as a vapour.

For the dermal long-term systemic DNEL, an in-vitro dermal absorption study performed on DOT(EHMA) (Ward, 2003) showed a very low absorption rate through the rat skin. Reading-across from this substance was considered appropriate, because both substances are liquid, with a high molecular weight (>500 g/mol), and may be too large to be absorbed though the skin. Moreover, their vapour pressure are very low. Although the rat skin is generally considered to be more permeable than human skin, as a worst-case assumption the same extent of dermal absorption (1%) has been used.

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:
DNEL (Derived No Effect Level)
Value:
41 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
Value:
8 200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
82 x (100/1)
AF for dose response relationship:
1
Justification:
use of a NOAEL as dose descriptor and the low toxicity of the test substance
AF for differences in duration of exposure:
2
Justification:
subchonic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat
AF for other interspecies differences:
1
Justification:
no difference in dermal absorption between rats and humans as worst-case assumption
AF for intraspecies differences:
10
Justification:
default for the general population
AF for the quality of the whole database:
1
Justification:
good quality of the whole database
AF for remaining uncertainties:
2.5
Justification:
Remaining differences
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.41 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
Value:
82 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
same extent of oral absorption in rats and humans
AF for dose response relationship:
1
Justification:
use of a NOAEL as dose descriptor and the low toxicity of the test substance
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat
AF for other interspecies differences:
1
Justification:
same extent of oral absorption in rats and humans
AF for intraspecies differences:
10
Justification:
default for the genral population
AF for the quality of the whole database:
1
Justification:
good quality of the whole database
AF for remaining uncertainties:
2.5
Justification:
remaining differences
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

The same endpoint used for setting the long-term systemic DNELs for workers has been used for deriving long-term systemic DNELs for the general population; the increased AF of 10 for intraspecies sensitivity has been considered to be sufficiently protective.


 


The inhalation route of exposure is considered to be not relevant for the general population and therefore no DNEL has been derived.