Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
DNEL value:
1.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL obtained in two occupational studies was 0.2 mg/kg/day. No correction factor for difference in absorption was applied because total absorption by inhalation was assumed (worst-case : occupational studies showed partial absorption, likely due to particle-size dependence). The concentration of 1.4 mg/m3 is obtained when considering a worker mean bodyweight of 70 kg and a respiratory volume of 10 m3 for a working day of 8 h.
AF for dose response relationship:
1
Justification:
A NOAEL was identified
AF for differences in duration of exposure:
1
Justification:
Chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Human to human extrapolation
AF for other interspecies differences:
1
Justification:
Human to human extrapolation
AF for intraspecies differences:
5
Justification:
The default AF is applied in a conservative approach althought the NOAEL was obtained in the same population (workers)
AF for the quality of the whole database:
1
Justification:
All relevant parameters assessed, reliable study
AF for remaining uncertainties:
1
Justification:
None
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEL
DNEL value:
10.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOAEL obtained in two occupational studies was 0.2 mg/kg/day. 1.85% absorption by dermal route is considered in humans based on sodium chlorate and read-across approach (see 7.1 and 7.1.2), leading to a point of departure of 0.2/0.0185 = 10.8 mg/kg/day.
AF for dose response relationship:
1
Justification:
A NOAEL was identified
AF for differences in duration of exposure:
1
Justification:
Chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Human to human extrapolation
AF for other interspecies differences:
1
Justification:
Human to human extrapolation
AF for intraspecies differences:
5
Justification:
The default AF is applied in a conservative approach althought the NOAEL was obtained in the same population (workers)
AF for the quality of the whole database:
1
Justification:
All relevant parameters assessed, reliable study
AF for remaining uncertainties:
1
Justification:
None
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:
low hazard (no threshold derived)

Additional information - workers

Two key studies, with equal weight, for repeat-dose toxicity of Ammonium Perchlorate: Braverman 2005 and Lamm 1999 occupational studies, with chronic exposure (around 6 years) to Ammonium Perchlorate mainly by inhalation. These were the most relevant values of a whole range of data on repeat-dose toxicity (in rats, mice and humans, with various durations). Both studies, carried out in the same manufacturing plant, led to the same systemic NOAEL of 0.20 mg/kg/day.

Starting point modification and the applied assessment factors are described and justified in the tables below.

Route of human exposure(for all lines)

Dermal

Inhalation

Repeated-dose DNEL, based on chronic occupational studies (two consistent K2 studies)

Point of departure:

0.20

mg/kg/day, NOAEL systemic value (converted from inhalative route)

 

Value

Justification

Value

Justification

Correction for difference in absorption:

1/0.0185

1.85% absorption by dermal route in human based on sodium chlorate and read-across

1

total absorption by inhalation assumed (worst-case : occupational studies showed partial absorption, likely due to particle-size dependence)

Corrected point of departure:

10.8

mg/kg/day, takes into account partial absorption

1.40

mg/m3, considers 10 m3/worker/8h, 70 kg/worker

Assessment Factor type, subtype

Value

Justification

Value

Justification

Interspecies, kinetics

1

human to human

Interspecies, other

1

Intraspecies, kinetics x dynamics

5

worker to worker : however the AF is applied as if the NOAEL represented the « mean » worker, in a worst-case

Exposure duration

1

chronic to chronic

Dose-response relationship

1

NOAEL. No data on dose-effect curve

Quality of whole database

1

all relevant parameters assessed, reliable study

Overall Assessment Factor

5

product of all above AFs

5

product of all above AFs

Resulting DNEL:

2.2

mg/kg/day

0.28

mg/m3


General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70 µg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
700 µg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL obtained in two occupational studies was 0.2 mg/kg/day. No correction factor for difference in absorption was applied because total absorption by inhalation was assumed (worst-case : occupational studies showed partial absorption, likely due to particle-size dependence). The concentration of 0.7 mg/m3 is obtained when considering a general population mean bodyweight of 70 kg and a respiratory volume of 20 m3 for a whole day of 24 h.
AF for dose response relationship:
1
Justification:
A NOAEL was identified
AF for differences in duration of exposure:
1
Justification:
Chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Human to human extrapolation
AF for other interspecies differences:
1
Justification:
Human to human extrapolation
AF for intraspecies differences:
10
Justification:
The default AF is applied in a conservative approach althought the NOAEL was obtained in a similar population (workers) (a factor of 2 is generally considered between workers and general population for intraspecies differences)
AF for the quality of the whole database:
1
Justification:
All relevant parameters assessed, reliable study
AF for remaining uncertainties:
1
Justification:
None
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
DNEL value:
0.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOAEL obtained in two occupational studies was 0.2 mg/kg/day. No correction factor for difference in absorption was applied because total absorption by inhalation was assumed (worst-case : occupational studies showed partial absorption, likely due to particle-size dependence).
AF for dose response relationship:
1
Justification:
A NOAEL was identified
AF for differences in duration of exposure:
1
Justification:
Chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Human to human extrapolation
AF for other interspecies differences:
1
Justification:
Human to human extrapolation
AF for intraspecies differences:
10
Justification:
The default AF is applied in a conservative approach althought the NOAEL was obtained in a similar population (workers) (a factor of 2 is generally considered between workers and general population for intraspecies differences)
AF for the quality of the whole database:
1
Justification:
All relevant parameters assessed, reliable study
AF for remaining uncertainties:
1
Justification:
None
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Two key studies, with equal weight, for repeat-dose toxicity of Ammonium Perchlorate: Braverman 2005 and Lamm 1999 occupational studies, with chronic exposure (around 6 years) to Ammonium Perchlorate mainly by inhalation. These were the most relevant values of a whole range of data on repeat-dose toxicity (in rats, mice and humans, with various durations). Both studies, carried out in the same manufacturing plant, led to the same systemic NOAEL of 0.20 mg/kg/day.

Starting point modification and the applied assessment factors are described and justified in the tables below.

Route of human exposure(for all lines)

Oral

Inhalation

Repeated-dose DNEL, based on chronic occupational studies (two consistent K2 studies)

Point of departure:

0.20

mg/kg/day, NOAEL systemic value (converted from inhalative route)

 

Value

Justification

Value

Justification

Correction for difference in absorption:

1

total absorption by oral route

1

total absorption by inhalation assumed (worst-case : occupational studies showed partial absorption, likely due to particle-size dependence)

Corrected point of departure:

0.20

mg/kg/day

0.70

mg/m3, considers 20 m3/person/24h, 70 kg/person

Assessment Factor type, subtype

Value

Justification

Value

Justification

Interspecies, kinetics

1

human to human

Interspecies, other

1

Intraspecies, kinetics x dynamics

10

worker to general population : however the AF is applied as if the NOAEL represented the « mean » worker, in a worst-case

Exposure duration

1

chronic to chronic

Dose-response relationship

1

NOAEL. No data on dose-effect curve

Quality of whole database

1

all relevant parameters assessed, reliable study

Overall Assessment Factor

10

product of all above AFs

10

product of all above AFs

Resulting DNEL:

20

µg/kg/day

70

µg/m3