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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:
16.33 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):
150
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
other: NAEC human worker
Value:
2 450 mg/m³
Explanation for the modification of the dose descriptor starting point:

NAEC human worker

[(NOEL 1000/4) x 70]/10;

NOEL= 1000 mg/kg bw day;

4= allometric scaling factor for rat;

70 kg/bw: mean human body weight;

10 mg/m^3 air default worker breathing volume

In  order  to  consider  the  difference  between  worker  exposure  (5  days)  and  experimental  exposure

conditions (7 days) = 1.4; the NAEC is multiplied by 1.4

1750*1.4 (NAEC*1.4) = 2450 mg/kg b.w day

AF for dose response relationship:
1
Justification:
Sufficient data about curve of dose/response. No additional severity factor.
AF for differences in duration of exposure:
6
Justification:
From sub acute to chronic (28 days)
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling needed because the starting point (NAEC human worker) has just been corrected for the human evaluation.
AF for other interspecies differences:
2.5
Justification:
Additional factor for other interspecies differences ( i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). Remaining differences.
AF for intraspecies differences:
5
Justification:
For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill.
AF for the quality of the whole database:
1
Justification:
Test in compliant with OECD and EU guidelines.
AF for remaining uncertainties:
2
Justification:
100% absorption for the inhalative route for animals and 50 % is adsorbed by oral route humans is assumed.
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:
4.67 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):
300
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Repeated oral study is the best way to assess the dermal route in absence of a repeated dermal study. In  order  to  consider  the  difference  between  worker  exposure  (5  days)  and  experimental  exposure conditions (7 days) = 1.4; the NOAEL is multiplied by 1.4

1000*1.4 (NOAEL*1.4) = 1400 mg/kg b.w day

AF for dose response relationship:
1
Justification:
Sufficient data about curve of dose/response. No additional severity factor.
AF for differences in duration of exposure:
6
Justification:
From sub acute to chronic (28 days)
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
Additional factor for other interspecies differences (i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). Remaining differences.
AF for intraspecies differences:
5
Justification:
For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill.
AF for the quality of the whole database:
1
Justification:
GLP compliant with OECD and EU guidelines.
AF for remaining uncertainties:
1
Justification:
Assuming 100% of absorption
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not a skin irritant, therefore no local effect is be expected.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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:
2.91 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):
300
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
other: NAEC
Value:
875 mg/m³
Explanation for the modification of the dose descriptor starting point:

NAEC (oral rat-Human gen. population)= [1000 mg/kg bw( NOAEL)/4 ((assessment factor interspecies) X 70 kg (human body weight): 20 m^3 (24h human breathing volume)]

AF for dose response relationship:
1
Justification:
Sufficient data about curve of dose/response. No additional severity factor.
AF for differences in duration of exposure:
6
Justification:
From sub acute to chronic (28 days)
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling needed because the starting point (NAEC human worker) has just been corrected for the human evaluation.
AF for other interspecies differences:
2.5
Justification:
Additional factor for other interspecies differences (i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). Remaining differences.
AF for intraspecies differences:
10
Justification:
For threshold effects, this factor of 10 is the standard procedure, as a default, when assessing exposure to the general population. It is recognised that there re differences between children and adults in toxicokinetics (especially babies in their first months) and toxicodynamics (especially at different stages of development). These differences may render children more or less susceptible to the toxic effects of a substance.
AF for the quality of the whole database:
1
Justification:
GLP compliant with OECD and EU guidelines.
AF for remaining uncertainties:
2
Justification:
100% absorption for the inhalative route for animals and 50 % is adsorbed by oral route humans is assumed.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No inhalatory repeated dose study has been performed; nevertheless the substance is not a respiratory irritant and is not classified for acute toxicity or skin sensitisation.

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:
1.67 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Repeated oral study is the best way to assess the dermal route in absence of a repeated dermal study.

AF for dose response relationship:
1
Justification:
Sufficient data about curve of dose/response. No additional severity factor.
AF for differences in duration of exposure:
6
Justification:
From sub acute to chronic (28 days)
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
Additional factor for other interspecies differences ( i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). Remaining differences.
AF for intraspecies differences:
10
Justification:
For threshold effects, this factor of 10 is the standard procedure, as a default, when assessing exposure to the general population. It is recognised that there re differences between children and adults in toxicokinetics (especially babies in their first months) and toxicodynamics (especially at different stages of development). These differences may render children more or less susceptible to the toxic effects of a substance.
AF for the quality of the whole database:
1
Justification:
GLP compliant with OECD and EU guidelines.
AF for remaining uncertainties:
1
Justification:
100% absorption for the inhalative route for animals and humans is assumed.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

 The substance is not a skin irritant, therefore no local effect is expected.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.67 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Sufficient data about curve of dose/response. No additional severity factor.
AF for differences in duration of exposure:
6
Justification:
From sub chronic to chronic (28 days)
AF for interspecies differences (allometric scaling):
4
Justification:
No allometric scaling needed because the starting point (NAEC human worker) has just been corrected for the human evaluation.
AF for other interspecies differences:
2.5
Justification:
Additional factor for other interspecies differences (i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). Remaining differences.
AF for intraspecies differences:
10
Justification:
For threshold effects, this factor of 10 is the standard procedure, as a default, when assessing exposure to the general population. It is recognised that there re differences between children and adults in toxicokinetics (especially babies in their first months) and toxicodynamics (especially at different stages of development). These differences may render children more or less susceptible to the toxic effects of a substance.
AF for the quality of the whole database:
1
Justification:
GLP compliant with OECD and EU guidelines.
AF for remaining uncertainties:
1
Justification:
No remaining uncertanties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not a skin irritant, therefore no local effect is expected.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population