Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.41 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
Dose descriptor starting point:
NOAEL
DNEL value:
40 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
35.26 mg/m³
Explanation for the modification of the dose descriptor starting point:

Repeated dose toxicity information is available from an oral sub-chronic toxicity study (OECD 408 - Repeated Dose 90-day Oral Toxicity Study in Rodents, see below). For inhalation exposure, route-to-route extrapolation is applied. The dose descriptor starting point is converted into the modified dose descriptor starting point using the following equation (see Guidance IR&CSA Chapter R.8, Figure R. 8-3, p 21):

correctedinhalatory NOAEC

= oral NOAEL x 1 / 0.38 (m³ / kg / d) x (Absoral-rat /Absinh-human) x 6.7 m³ (RV: 8h, standard) / 10 m³ (RV: 8h, light work)

= 40 x 1/0.38 x 0.5/1 x 6.7/10

= 35.26 mg/m³

AF for differences in duration of exposure:
2
Justification:
sub-chronic (90/100 d) to chronic extrapolation factor
AF for interspecies differences (allometric scaling):
1
Justification:
already included in route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
default AF
AF for intraspecies differences:
5
Justification:
default AF for workers
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
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:
3.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 050 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL originates from a 28 d dermal repeated-dose toxicity study. Correction for differences in experimental and worker exposure conditions (dermal dose application for 7 days per week and 6 hours per day versus dermal worker exposure at only 5 days per week and 8 hours per day) results in a corrected/modified dose descriptor starting point of 1050 mg/kg w/day (1000 mg/kg bw/day x 7/5 (days per week) x 6/8 (hours per day).

AF for differences in duration of exposure:
6
Justification:
subacute (28 d) to chronic extrapolation factor
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling from rat to man
AF for other interspecies differences:
2.5
Justification:
default AF
AF for intraspecies differences:
5
Justification:
default AF for worker
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.348 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
Dose descriptor starting point:
NOAEL
DNEL value:
40 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
17.39 mg/m³
Explanation for the modification of the dose descriptor starting point:

Repeated dose toxicity information is available from an oral sub-chronic toxicity study (OECD 408 - Repeated Dose 90 -day Oral Toxicity Study in Rodents, see below). For inhalation exposure, route-to-route extrapolation is applied. The dose descriptor starting point is converted into the modified dose descriptor starting point using the following equation (see Guidance IR&CSA Chapter R.8, Figure R. 8-3, p 21):

correctedinhalatory NOAEC

= oral NOAEL x 1 / 1.15 (m³ / kg / d) x (Absoral-rat /Absinh-human)

= 40 x 1/1.15 x 0.5/1

= 17.39 mg/m³

AF for differences in duration of exposure:
2
Justification:
sub-chronic (90/100 d) to chronic extrapolation factor
AF for interspecies differences (allometric scaling):
1
Justification:
already included in route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
default AF
AF for intraspecies differences:
10
Justification:
default AF for general population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
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:
0.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL originates from a 28 d dermal repeated-dose toxicity study with rats. Correction for differences in experimental and general population exposure conditions (dermal dose application for 7 days per week and 6 hours per day versus dermal general population exposure at 7 days per week and 24 hours per day) results in a corrected/modified dose descriptor starting point of 250 mg/kg bw/day (1000 mg/kg bw/day x 6/24 (hours per day).

AF for differences in duration of exposure:
6
Justification:
subacute (28 d) to chronic extrapolation factor
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling from rat to man
AF for other interspecies differences:
2.5
Justification:
default AF
AF for intraspecies differences:
10
Justification:
default AF for general population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.2 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
Dose descriptor starting point:
NOAEL
DNEL value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point (NOAEL) originates from an oral sub-chronic repeated dose toxicity study (OECD 408 - Repeated Dose 90-day Oral Toxicity Study in Rodents, see below). Adjustment/correction of the dose descriptor starting point (40 mg/kg bw/day) is not required.

AF for differences in duration of exposure:
2
Justification:
sub-chronic (90/100 d) to chronic extrapolation factor
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling from rat to man
AF for other interspecies differences:
2.5
Justification:
default AF
AF for intraspecies differences:
10
Justification:
default AF for general population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population