Copper(2+), bis[N-[amino(imino-.kappa.N)methyl]urea-.kappa.O]-, nitrate (1:2)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.35 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:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

176 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 407 repeated dose oral toxicity study in rats resulted to a NOAEL of 200 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)) = 200 mg/kg/d*(1/0.38 m³/kg/d) *(0.5*1) *0.67= 176 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 28 day study (sub-acute). 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:

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

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

21.16 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:

264.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 402 acute dermal toxicity study in rats resulted to an NOEL of 2000 mg/kg/day after 24 hours of cutaneous exposure. An OECD 423 acute oral toxicity study in rats resulted to a NOEL of 300 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)) = 300 mg/kg/d*(1/0.38 m³/kg/d) *(0.5*1) *0.67= 264.5 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 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

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

0.67 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:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 407 repeated dose oral toxicity study in rats resulted to a NOAEL of 200 mg/kg/day. According the guidance, the following route to route extrapolation is realized : NOAECcorr=NOAELoral*(ABSoral- rat/ABScut-human) = 200 mg/kg/d*(1) = 200 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 NOAEL.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral 28 day study (sub-acute). The guidance indicates that for subacute to chronic a factor 6 should be applied.

AF for interspecies differences (allometric scaling):

4

Justification:

According to the guidance, 4 is the allometric scaling factors 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

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:

Dermal

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

AF for dose response relationship:

1

Justification:

Starting point is NOEL.

AF for interspecies differences (allometric scaling):

4

Justification:

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

AF for other interspecies differences:

2.5

Justification:

In an 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

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.28 mg/cm²

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

other: NOEL (mg/cm²)

Value:

13.8

AF for dose response relationship:

1

Justification:

Starting point is NOEL of 2000 mg/kg converted in mg/cm².

AF for interspecies differences (allometric scaling):

4

Justification:

According to the guidance, allometric scaling should not be applied for local effects which are not dependent on metabolic rate or systemic absorption. However, no kinetic data are available.

AF for other interspecies differences:

2.5

Justification:

According to the guidance, default factor for remaining uncertainties for local effects is needed if tissue metabolism is involved. No kinetic data are available. Thus,on the safe side, a default 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

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:

1.17 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:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

176 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 407 repeated dose oral toxicity study in rats resulted to a NOAEL of 200 mg/kg/day. According 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)) = 200 mg/kg/d*(1/0.38 m³/kg/d) *(0.5*1) *0.67= 176 mg/m³ ; It is assumed that default oral absorption rate is 50% of that of inhalation absorption. 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 28 day study (sub-acute). The guidance indicates that for subacute to chronic 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 an 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

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.6 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:

264.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 402 acute dermal toxicity study in rats resulted to a NOEL of 2000 mg/kg/day after 24 hours of cutaneous exposure. An OECD 423 acute oral toxicity study in rats resulted to an NOEL of 300 mg/kg/day. According the guidance, the following route to route extrapolation is realized for the worst case (extrapolation from oral route) : NOAECcorr=NOAELoral*(1/0.38 m³/kg/d) *(ABSoral- rat/ABSinh-human) *(6.7 m³ (8h) /10 m³ (8h)) = 300 mg/kg/d*(1/0.38 m³/kg/d) *(0.5*1) *0.67= 264.5 mg/m³ ; It is assumed that default oral absorption rate is 50% of that of inhalation absorption. ABSoral/rat=oral absorption rate in rats, ABSinh. /human=inhalation absorption rate in humans.

AF for dose response relationship:

1

Justification:

Starting point is NOEL.

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in the NOEC calculation.

AF for other interspecies differences:

2.5

Justification:

In an 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

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

0.33 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:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 407 repeated dose oral toxicity study in rats resulted to a NOAEL of 200 mg/kg/day. According the guidance, the following route to route extrapolation is realized : NOAECcorr=NOAELoral*(ABSoral- rat/ABScut-human) = 200 mg/kg/d*(1) = 200 mg/m³ ; 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 NOAEL.

AF for differences in duration of exposure:

6

Justification:

DNEL is based on an oral 28 day study (sub-acute). 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 an 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

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:

Dermal

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

AF for dose response relationship:

1

Justification:

Starting point is 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 an 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

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.14 mg/cm²

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

other: NOEL (mg/cm²)

Value:

13.8

AF for dose response relationship:

1

Justification:

Starting point is NOEL of 2000 mg/kg converted in mg/cm².

AF for interspecies differences (allometric scaling):

4

Justification:

According to the guidance, allometric scaling should not be applied for local effects which are not dependent on metabolic rate or systemic absorption. However, no kinetic data are available.

AF for other interspecies differences:

2.5

Justification:

According to the guidance, default factor for remaining uncertainties for local effects is needed if tissue metabolism is involved. No data kinetic is available. Thus, on the safe side, a default 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

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.33 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:

200 mg/kg bw/day

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 28 day study (sub-acute)

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling factor for rats as compared to humans

AF for other interspecies differences:

2.5

Justification:

According to the guidance, default factor for remaining uncertainties for local effects is needed if tissue metabolism is involved. No data kinetic is available. Thus,on the safe side, a default 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

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3 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:

300 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Starting point is NOEL.

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling factor for rats as compared to humans

AF for other interspecies differences:

2.5

Justification:

According to the guidance, default factor for remaining uncertainties for local effects is needed if tissue metabolism is involved. No data kinetic is available. Thus,on the safe side, a default 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)