Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.234 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):
35
Modified dose descriptor starting point:
NOAEC
Value:
1 163.19 mg/m³
Explanation for the modification of the dose descriptor starting point:
Exposure data available only from oral exposure data
AF for dose response relationship:
1
Justification:
Table R8-6
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic. Table R8-6
AF for interspecies differences (allometric scaling):
1.4
Justification:
Dog to human data. Table R8-3
AF for intraspecies differences:
5
Justification:
Worker. Table R8-6
AF for the quality of the whole database:
1
Justification:
Data reliable. Table R8-6
AF for remaining uncertainties:
2.5
Justification:
Table R8-6
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:
7.14 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):
35
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Exposure data available only from oral exposure data.
AF for dose response relationship:
1
Justification:
Table R8-6
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic. Table R8-6
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog to human data. Table R8-3
AF for intraspecies differences:
5
Justification:
workers. Table R8-6
AF for the quality of the whole database:
1
Justification:
data reliable. Table R8-6
AF for remaining uncertainties:
2.5
Justification:
Table R8-6
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Dermal NOAEL

Based on Appendix R. 8-2, Example B.5, as a worst case it is assumed that 100% adsorption orally to rats and by dermal adsorption to human are equivalent.

NOAEL (dermal) = 250 * 100/100

NOAEL (dermal) = 250 mg/kg/day.

Inhalation NOAEL

Calculation of inhalation NOAEL is based on formulae in R. 8 -3, as a worst case it is assumed 100% adsorption orally to rats and by inhalation to human are equivalent with suitable modification to account for test species being canine rather than rat. The granulometry data for this substance indicates that the substance is not respirable by humans; the vapour pressure of the substance is extremely low indicating the substance is non-volatile. Target endpoints are also assumed to be equivalent.

Canine respiration rate determined based on principles outlined in Handbook of Veterinary Nursing, H. Orpet, P. Welsh, 2002 Blackwell Science Ltd, ISBN:9780632052585

Assumptions made:

Tidal volume (canine) 10 ml/kg bw

Respiration rate 20 breaths per minute

Circuit factor 1.5

Respiratory volume (canine) = 10 x 20 x 1.5 = 300 ml/min/kg bw = 0.3l/min/kg bw

8h exposure = 0.3 x 0.001 x 60 x 8 = 0.144 m3/kg bw

For workers (8h exposure/d)

NOAEL (inhal) = 250 * 1/0.144 m3/kg/d * 100/100 * 6.7m3/10m3

NOAEL (inhal) = 1163.19 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.27 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):
70
Modified dose descriptor starting point:
NOAEC
Value:
578.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
Exposure data available only from oral exposure data
AF for dose response relationship:
1
Justification:
Table R8-6
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic. Table R8-6
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog to human data. Table R8-3
AF for intraspecies differences:
10
Justification:
general population. Table R8-6
AF for the quality of the whole database:
1
Justification:
data reliable. Table R8-6
AF for remaining uncertainties:
2.5
Justification:
Table R8-6
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:
3.57 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):
70
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Exposure data only available from oral exposure data.
AF for dose response relationship:
1
Justification:
Table R8-6
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic. Table R8-6
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog to human data. Table R8-3
AF for intraspecies differences:
10
Justification:
general population. Table R8-6
AF for the quality of the whole database:
1
Justification:
data reliable. Table R8-6
AF for remaining uncertainties:
2.5
Justification:
Table R8-6
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

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:
3.57 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):
70
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Table R8-6
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic. Table R8-6
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog to human data. Table R8-3
AF for intraspecies differences:
10
Justification:
general population. Table R8-6
AF for the quality of the whole database:
1
Justification:
data reliable. Table R8-6
AF for remaining uncertainties:
2.5
Justification:
Table R8-6
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

Dermal NOAEL

Based on Appendix R. 8-2, Example B.5, as a worst case it is assumed that 100% adsorption orally to rats and by dermal adsorption to human are equivalent.

NOAEL (dermal) = 250 * 100/100

NOAEL (dermal) = 250 mg/kg/day

Inhalation NOAEL

Calculation of inhalation NOAEL is based on formulae in R. 8 -3, as a worst case it is assumed 100% adsorption orally to rats and by inhalation to human are equivalent with suitable modification to account for test species being canine rather than rat. The granulometry data for this substance indicates that the substance is not respirable by humans; the vapour pressure of the substance is extremely low indicating the substance is non-volatile. Target endpoints are also assumed to be equivalent.

Canine respiration rate determined based on principles outlined in Handbook of Veterinary Nursing, H. Orpet, P. Welsh, 2002 Blackwell Science Ltd, ISBN:9780632052585

Assumptions made:

Tidal volume (canine) 10 ml/kg bw

Respiration rate 20 breaths per minute

Circuit factor 1.5

Respiratory volume (canine) = 10 x 20 x 1.5 = 300 ml/min/kg bw = 0.3l/min/kg bw

24h exposure = 0.3 x 0.001 x 60 x 24 = 0.432 m3/kg bw

For workers (8h exposure/d)

NOAEL (inhal) = 250 * 1/0.432 m3/kg/d * 100/100

NOAEL (inhal) = 578.70 mg/m3