Copper, diammine[5,5'-bi-1H-tetrazolato(2-)-kN1, kN1']

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13.3 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):

75

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

882 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 422 Combined Repeated Oral Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening in Wistar rats resulted to a NOAEL of 1,000 mg/kg/day. According to the guidance, the following route to route extrapolation is realized : NOAECcorr=NOAELoral*(1/0.38 m³/kg/d) *(ABSoral- rat/ABSinh-human) *(6.7 m³ (8h) /10 m³ (8h)) = 1,000 mg/kg/d*(1/0.38 m³/kg/d) *(0.5*1) *0.67= 882 mg/m³ ; It is assumed that default oral absorption rate is 50% of that of inhalation absorption (default factor of the R8 guidance, regarding to particle size, this consideration is conservative). ABSoral/rat=oral absorption rate in rats, ABSinh. /human=inhalation absorption rate in humans

AF for dose response relationship:

1

Justification:

Starting point is NOAEL.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (equivalent to a sub-acute study). The guidance indicates that for subacute to chronic extrapolation a factor 6 sould be applied.

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in the NOAEC calculation.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

5

Justification:

According to the guidance, 5 is the default assessment factor for workers.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

141.1 mg/m³

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

Dose descriptor starting point:

other: NOEL

Value:

2 000 mg/kg bw/day

Modified dose descriptor starting point:

other: NOEC

Value:

1 763.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 423 acute oral toxicity study in rats resulted to a NOEL of 2,000 mg/kg/day. According the guidance, the following route to route extrapolation is realized (extrapolation from oral route) : NOAECcorr=NOAELoral*(1/0.38 m³/kg/d) *(ABSoral- rat/ABSinh-human) *(6.7 m³(8h) /10 m³(8h)) = 2000 mg/kg/d*(1/0.38 m³/kg/d) *(0.5*1) *0.67= 1763.2 mg/m³; It is assumed that default oral absorption rate is 50% of that of inhalation absorption (default factor of the R8 guidance, regarding to particle size, this consideration is conservative). ABSoral/rat=oral absorption rate in rats, ABSinh. /human=inhalation absorption rate in humans.

AF for dose response relationship:

1

Justification:

Starting point is a NOEL.

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in the NOEC calculation.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

5

Justification:

According to the guidance, 5 is the default assessment factor for workers.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.3 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):

300

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 422 Combined Repeated Oral Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening in Wistar rats resulted to a NOAEL of 1,000 mg/kg/day. According the guidance, the following route to route extrapolation is realized : NOAECcorr=NOAELoral*(ABSoral- rat/ABScut-human) = 1,000 mg/kg/d*(1) = 1,000 mg/kg/day ; By default, it is assumed that oral and dermal absorption rates are equal, ABSoral/rat=oral absorption  rate in rats, ABScut. /human=cutaneaous absorption rate in humans.

AF for dose response relationship:

1

Justification:

Starting point is the NOAEL.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (equivalent to a sub-acute study). The guidance indicates that for subacute to chronic extrapolation a factor 6 should be applied.

AF for interspecies differences (allometric scaling):

4

Justification:

According to the guidance, 4 is the allometric scaling factor for rats.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

5

Justification:

According to the guidance, 5 is the default assessment factor for workers.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

40 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

other: NOEL

Value:

2 000 mg/kg bw/day

Modified dose descriptor starting point:

other: NOEL

Value:

2 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 423 acute oral toxicity study in rats resulted to a NOEL of 2,000 mg/kg/day.

According the guidance, the following route to route extrapolation is realized : NOAECcorr=NOAELoral*(ABSoral- rat/ABScut-human) = 2,000 mg/kg/d*(1) = 2,000 mg/kg/day ; By default, it is assumed that oral and dermal absorption rates are equal, ABSoral/rat=oral absorption  rate in rats, ABScut. /human=cutaneaous absorption rate in humans.

AF for dose response relationship:

1

Justification:

Starting point is a NOEL.

AF for interspecies differences (allometric scaling):

4

Justification:

According to the guidance, 4 is the allometric scaling factor for rats.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

5

Justification:

According to the guidance, 5 is the default assessment factor for workers.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.9 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):

150

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

882 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 422 Combined Repeated Oral Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening in Wistar rats resulted to a NOAEL of 1,000 mg/kg/day. According to the guidance, the following route to route extrapolation is realized : NOAECcorr=NOAELoral*(1/0.38 m³/kg/d) *(ABSoral- rat/ABSinh-human) *(6.7 m³ (8h) /10 m³ (8h)) = 1,000 mg/kg/d*(1/0.38 m³/kg/d) *(0.5*1) *0.67= 882 mg/m³ ; It is assumed that default oral absorption rate is 50% of that of inhalation absorption (default factor of the R8 guidance, regarding to particle size, this consideration is conservative). ABSoral/rat=oral absorption  rate in rats, ABSinh. /human=inhalation absorption rate in humans

AF for dose response relationship:

1

Justification:

Starting point is NOAEL.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (equivalent to a sub-acute study). The guidance indicates that for subacute to chronic extrapolation a factor 6 should be applied.

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in the NOAEC calculation.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

10

Justification:

According to the guidance, 10 is the default assessment factor for general population.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

70.5 mg/m³

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

other: NOEL

Value:

2 000 mg/kg bw/day

Modified dose descriptor starting point:

other: NOEC

Value:

1 763.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 423 acute oral toxicity study in rats resulted to a NOEL of 2,000 mg/kg/day. According the guidance, the following route to route extrapolation is realized (extrapolation from oral route) : NOAECcorr=NOAELoral*(1/0.38 m³/kg/d) *(ABSoral- rat/ABSinh-human) *(6.7 m³(8h) /10 m³(8h)) = 2000 mg/kg/d*(1/0.38 m³/kg/d) *(0.5*1) *0.67= 1763.2 mg/m³; It is assumed that default oral absorption rate is 50% of that of inhalation absorption (default factor of the R8 guidance, regarding to particle size, this consideration is conservative). ABSoral/rat=oral absorption rate in rats, ABSinh. /human=inhalation absorption rate in humans.

AF for dose response relationship:

1

Justification:

Starting point is a NOEL.

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in the NOEC calculation.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

10

Justification:

According to the guidance, 10 is the default assessment factor for general population.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.7 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):

600

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 422 Combined Repeated Oral Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening in Wistar rats resulted to a NOAEL of 1,000 mg/kg/day. According the guidance, the following route to route extrapolation is realized : NOAECcorr=NOAELoral*(ABSoral- rat/ABScut-human) = 1,000 mg/kg/d*(1) = 1,000 mg/kg/day ; By default, it is assumed that oral and dermal absorption rates are equal, ABSoral/rat=oral absorption  rate in rats, ABScut. /human=cutaneaous absorption rate in humans.

AF for dose response relationship:

1

Justification:

Starting point is the NOAEL.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (equivalent to a sub-acute study). The guidance indicates that for subacute to chronic extrapolation a factor 6 should be applied.

AF for interspecies differences (allometric scaling):

4

Justification:

According to the guidance, 4 is the allometric scaling factor for rats.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

10

Justification:

According to the guidance, 10 is the default assessment factor for general population.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

other: NOEL

Value:

2 000 mg/kg bw/day

Modified dose descriptor starting point:

other: NOEL

Value:

2 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 423 acute oral toxicity study in rats resulted to a NOEL of 2,000 mg/kg/day.

According the guidance, the following route to route extrapolation is realized : NOAECcorr=NOAELoral*(ABSoral- rat/ABScut-human) = 2,000 mg/kg/d*(1) = 2,000 mg/kg/day ; By default, it is assumed that oral and dermal absorption rates are equal, ABSoral/rat=oral absorption  rate in rats, ABScut. /human=cutaneaous absorption rate in humans.

AF for dose response relationship:

1

Justification:

Starting point is a NOEL.

AF for interspecies differences (allometric scaling):

4

Justification:

According to the guidance, 4 is the allometric scaling factor for rats.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

10

Justification:

According to the guidance, 10 is the default assessment factor for general population.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.7 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):

600

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Starting point is a NOAEL.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (equivalent to a sub-acute study). The guidance indicates that for subacute to chronic extrapolation a factor 6 should be applied.

AF for interspecies differences (allometric scaling):

4

Justification:

According to the guidance, 4 is the allometric scaling factor for rats.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

10

Justification:

According to the guidance, 10 is the default assessment factor for general population.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

other: NOEC

Value:

2 000 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Starting point is a NOEL.

AF for interspecies differences (allometric scaling):

4

Justification:

According to the guidance, 4 is the allometric scaling factor for rats.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific data on interspecies differences (toxicokinetic and toxicodynamic differences) an additional factor of 2.5 is applied.

AF for intraspecies differences:

10

Justification:

According to the guidance, 10 is the default assessment factor for general population.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results.

AF for remaining uncertainties:

1

Justification:

No specific concerns (an additional factor to address genotoxicity deficiencies could have been retained here, however, a qualitative risk assessment was conducted in the CSR to consider this gap)

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified