Diphosphoric acid, compound with 1,3,5-triazine-2,4,6-triamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.529 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

Value:

15 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

13.22 mg/m³

Explanation for the modification of the dose descriptor starting point:

Most sensitive endpoint is for oral exposure and there are no long term toxicity data available via the inhalation route.

The dose descriptor staring point was derived from the most sensitive toxicity endpoint which is the 28-day repeat oral toxicity NOAEL of 15 mg/kg/day. According to Table 2 of ECHA practical guide 14,

For workers inhalation NOAEC:

Inhalatory NOAEC= oral NOAEL*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.)=15mg/kg/d *(1/0.38 m3/kg/d)*0.67*0.5/1=13.22 mg/m3

AF for dose response relationship:

1

Justification:

default factor for starting point for DNEL derivation NOAEL

AF for differences in duration of exposure:

2

Justification:

although the study is a 28-day study, use of an AF for 90-day study is considered appropriate as it is considered that the repeat dose toxicity of MPP is sufficiently characterized in the available data and that subchronic toxicity testing would be unlikely to provide further relevant information.

AF for interspecies differences (allometric scaling):

1

Justification:

not needed for inhalation DNEL

AF for other interspecies differences:

2.5

Justification:

default value

AF for intraspecies differences:

5

Justification:

default value

AF for the quality of the whole database:

1

Justification:

the key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties:

1

Justification:

no other uncertainties

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:

0.15 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):

100

Dose descriptor starting point:

NOAEL

Value:

15 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

15 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Most sensitive endpoint is for oral exposure and there are no long term toxicity data available via the dermal route.

The dose descriptor staring point was derived from the most sensitive toxicity endpoint which is the 28-day repeat oral toxicity NOAEL of 15 mg/kg/day. According to Table 2 of ECHA practical guide 14, NOAEL oral =NOAEL dermal x (absorption oral/absorption dermal). In the absence of any data it is assumed that 100% absorption occurs for both oral and dermal routes and therefore NOAEL oral = NOAEL dermal = 15mg/kg/day.  

AF for dose response relationship:

1

Justification:

default factor for starting point for DNEL derivation NOAEL

AF for differences in duration of exposure:

2

Justification:

although the study is a 28-day study, use of an AF for 90-day study is considered appropriate as it is considered that the repeat dose toxicity of MPP is sufficiently characterized in the available data and that subchronic toxicity testing would be unlikely to provide further relevant information.

AF for interspecies differences (allometric scaling):

4

Justification:

allometric scaling factor for the rat

AF for other interspecies differences:

2.5

Justification:

default value

AF for intraspecies differences:

5

Justification:

default value

AF for the quality of the whole database:

1

Justification:

the key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties:

1

Justification:

no other uncertainties

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:

medium hazard (no threshold derived)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.13 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

Value:

15 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

6.52 mg/m³

Explanation for the modification of the dose descriptor starting point:

Most sensitive endpoint is for oral exposure and there are no long term toxicity data available via the inhalation route.

The dose descriptor staring point was derived from the most sensitive toxicity endpoint which is the 28-day repeat oral toxicity NOAEL of 15 mg/kg/day. According to Table 2 of ECHA practical guide 14,

For general population inhalation NOAEC:

Inhalatory NOAECcorr=NOAELoral*(1/1.15 m3/kg/d)*(ABSoral-rat/ABSinh-human) = 15 mg/kg/d*(1/1.15 m3/kg/d)*(0.5/1)=6.52 mg/m3

AF for dose response relationship:

1

Justification:

default factor for starting point for DNEL derivation NOAEL

AF for differences in duration of exposure:

2

Justification:

although the study is a 28-day study, use of an AF for 90-day study is considered appropriate as it is considered that the repeat dose toxicity of MPP is sufficiently characterized in the available data and that subchronic toxicity testing would be unlikely to provide further relevant information.

AF for interspecies differences (allometric scaling):

1

Justification:

not needed for inhalation DNEL

AF for other interspecies differences:

2.5

Justification:

default value

AF for intraspecies differences:

10

Justification:

default value

AF for the quality of the whole database:

1

Justification:

the key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties:

1

Justification:

no other uncertainties

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:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.075 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

Value:

15 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

15 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Most sensitive endpoint is for oral exposure and there are no long term toxicity data available via the dermal route.

The dose descriptor starting point was derived from the most sensitive toxicity endpoint which is the 28-day repeat oral toxicity NOAEL of 15 mg/kg/day. According to Table 2 of ECHA practical guide 14, NOAEL oral =NOAEL dermal x (absorption oral/absorption dermal). In the absence of any data it is assumed that 100% absorption occurs for both oral and dermal routes and therefore NOAEL oral = NOAEL dermal = 15mg/kg/day.  

AF for dose response relationship:

1

Justification:

default factor for starting point for DNEL derivation NOAEL

AF for differences in duration of exposure:

2

Justification:

although the study is a 28-day study, use of an AF for 90-day study is considered appropriate as it is considered that the repeat dose toxicity of MPP is sufficiently characterized in the available data and that subchronic toxicity testing would be unlikely to provide further relevant information.

AF for interspecies differences (allometric scaling):

4

Justification:

allometric scaling factor for the rat

AF for other interspecies differences:

2.5

Justification:

default value

AF for intraspecies differences:

10

Justification:

default value

AF for the quality of the whole database:

1

Justification:

The key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties:

1

Justification:

No other uncertainties

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:

0.075 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

Value:

15 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

not applicable - route to route extrapolation is not required

AF for dose response relationship:

1

Justification:

Default factor for starting point for DNEL derivation NOAEL

AF for differences in duration of exposure:

2

Justification:

although the study is a 28-day study, use of an AF for 90-day study is considered appropriate as it is considered that the repeat dose toxicity of MPP is sufficiently characterized in the available data and that subchronic toxicity testing would be unlikely to provide further relevant information.

AF for interspecies differences (allometric scaling):

4

Justification:

allometeric scaling factor for the rat

AF for other interspecies differences:

2.5

Justification:

default value

AF for intraspecies differences:

10

Justification:

default value

AF for the quality of the whole database:

1

Justification:

The key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)