Ammonium perchlorate

Toxicological Summary

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

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

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

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

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