A 2:1:1 mixture of: trisodium N(1')-N(2):N(1''')-N(2'')-η-6-[2-amino-4-(or 6)-hydroxy-(or 4-amino-2-hydroxy)phenylazo]-6''-(1-carbaniloyl-2-hydroxyprop-1-enylazo)-5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'-azobenzene-1,2'-diolato-O(1),O(2'))-chromate; trisodium N(1')-N(2):N(1''')-N(2'')-η-6,6''-bis(1-carbaniloyl-2-hydroxyprop-1-enylazo)-5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'azobenzene-1,2'-diolato-O(1),O(2'))-chromate; trisodium N(1')-N(2):N(1''')-N(2'')-η-6,6''-bis[2-amino-4-(or 6)-hydroxy-(or 4-amino-2-hydroxy)phenylazo]5',5'''-disulfamoyl-3,3''-disulfonatobis(naphthalene-2,1'azobenzene-1,2'-diolato-O(1),O(2'))-chromate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.64 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:

100 mg/kg bw/day

Modified dose descriptor starting point:

other: NAEC

Value:

123 mg/m³

Explanation for the modification of the dose descriptor starting point:

NOAEL (No Observed Adverse Effect Level) on females for general toxicity by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: exposure route, study duration, presence of adverse effects, parameters observed.

Starting from an oral NOAEL, a corrected value is obtained considering: 8h- breathing volume of rat (0.38 m³/kg bw), 8h- breathing volume of human general population (6.7 m³), 8 h- workers (10 m³) and correction for differences between human and experimental exposure conditions (7 d /5 d). As no experimental data on absorption by inhalation is available, worst case assumption for absorption is applied: 50 % orally and 100 % by inhalation.

NAEC inh for worker = 100 mg/kg bw/d / (0.38 m³/kg bw) × (6.7 m³/10 m³(8h)) × (7 d /5 d) × 0.5

AF for dose response relationship:

1

Justification:

NOAEL used for NAEC derivation

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

allometric scaling has been already considered in starting point derivation

AF for other interspecies differences:

2.5

Justification:

toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)

AF for intraspecies differences:

5

Justification:

workers

AF for the quality of the whole database:

1

Justification:

good quality of available data

AF for remaining uncertainties:

1

Justification:

no significant uncertainties remaining

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

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:

0.467 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:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

140 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NOAEL (No Observed Adverse Effect Level) on females for general toxicity by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: exposure route, study duration, presence of adverse effects, parameters observed.

Starting from an oral NOAEL, a corrected value is obtained considering: the correction for differences between human and experimental exposure conditions (7 d /5 d)

Based on the assumption that dermal absorption is not generally higher than oral absorption, no default factor for bioavailability should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:

1

Justification:

NOAEL (oral) used

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

study performed on rat

AF for other interspecies differences:

2.5

Justification:

toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)

AF for intraspecies differences:

5

Justification:

workers

AF for the quality of the whole database:

1

Justification:

good quality of available data

AF for remaining uncertainties:

1

Justification:

no significant uncertainties remaining

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

The DNELs (Derived No Effect Levels) for both inhalation and dermal long-term exposures related to systemic effects, are estimated starting from the NOAEL (No Observed Adverse Effect Level) for oral route. Specifically, the NOAEL considered is the one obtained on females for general toxicity by oral route determined in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route); it is selected as the most representative starting dose based on: exposure route, study duration, presence of adverse effects, parameters observed. Therefore, the calculation of NOAEL_{inhalation, dermal} should be done considering the differences between the experimental conditions and the real human exposure situation.

In order to accout the interspecies difference between rat and human, variability and uncertainty within and between species the NOAEL has to be corrected, using the appropriate assessment factors for DNEL calculation.

No DNEL is derived for inhalation acute exposure related to systemic effects, as, based on the physicochemical properties (i.e. negligible vapour pressure and inhalable fraction particle size) inhalation is not an appropriate route of exposure. Analogously, no DNEL via inhalation route is derived for either long-term or acute local effects because significant exposure is unlikely to occur. In addition, it should be noted that the applied RMM and OCs contribute to minimised the possibility of inhalation exposure.

No DNEL is derived for dermal acute exposure, systemic and local effects, because no acute toxicity potential and no skin irritation were observed in short term studies (i.e. acute dermal toxicity and skin irritation/corrosion)

Since no substance-related local effects were observed in short term studies (i.e. acute dermal toxicity and skin irritation/corrosion), only the DNEL for long-term dermal systemic effects is derived.

Regarding the hazard for eyes, the substance can be considered as medium hazardous, based on its potential to cause eye damage according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Part E: Risk Characterisation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.29 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:

100 mg/kg bw/day

Modified dose descriptor starting point:

other: NAEC

Value:

43.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL (No Observed Adverse Effect Level) for general toxicity by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: expusure route, study duration, presence of adverse effects, parameters observed.

Starting from an oral NOAEL, a corrected value is obtained considering: 24 h- breathing volume of rat (1.15 m³/kg bw) and 24 h- breathing volume of human general population (20 m³). As no experimental data on absorption by inhalation is available, worst case assumption for absorption is applied: 50 % orally and 100 % by inhalation.

NAEC inh for general public = 100 mg/kg bw/d / (1.15 m³/kg bw) × 0.5

AF for dose response relationship:

1

Justification:

NOAEL used for NAEC derivation

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

allometric scaling has been already considered in starting point derivation

AF for other interspecies differences:

2.5

Justification:

toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

good quality of available data

AF for remaining uncertainties:

1

Justification:

no significant uncertainties remaining

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

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:

0.167 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:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NOAEL (No Observed Adverse Effect Level) on females for general toxicity by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: exposure route, study duration, presence of adverse effects, parameters observed.

Based on the assumption that dermal absorption is not generally higher than oral absorption, no default factor for bioavailability should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:

1

Justification:

NOAEL (oral) used

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

study performed on rat

AF for other interspecies differences:

2.5

Justification:

toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

good quality of available data

AF for remaining uncertainties:

1

Justification:

no significant uncertainties remaining

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.167 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:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The modification of dose description is not necessary, as NOAEL on females for general toxicity by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: study duration, presence of adverse effects, parameters observed.

AF for dose response relationship:

1

Justification:

NOAEL was used as a starting point

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rats were used in the available test

AF for other interspecies differences:

2.5

Justification:

toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

good quality of available data

AF for remaining uncertainties:

1

Justification:

no other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

The DNELs (Derived No Effect Levels) for inhalation, dermal and oral long-term exposures related to systemic effects, are estimated starting from the NOAEL (No Observed Adverse Effect Level) for oral route. Specifically, the NOAEL considered is the one obtained on females for general toxicity by oral route determined in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route); it is selected as the most representative starting dose based on: exposure route, study duration, presence of adverse effects, parameters observed.Therefore, the calculation of NOAEL_{inhalation, dermal, oral} should be done considering the differences between the experimental conditions and the real human exposure situation. In order to accout the interspecies difference between rat and human, variability and uncertainty within and between speciesthe NOAEL has to be corrected, using the appropriate assessment factors for DNEL calculation.

No DNEL is derived for inhalation acute exposure related to systemic effects, as, based on the physicochemical properties (i.e. negligible vapour pressure and inhalable fraction particle size) inhalation is not an appropriate route of exposure. Analogously, no DNEL via inhalation route is derived for either long-term or acute local effects because significant exposure is unlikely to occur. In addition, it should be noted that the applied RMM and OCs contribute to minimised the possibility of inhalation exposure.

No DNEL is derived for dermal acute exposure, systemic and local effects, because no acute toxicity potential and no skin irritation were observed in short term studies (i.e. acute dermal toxicity and skin irritation/corrosion)

Since no substance-related local effects were observed in short term studies (i.e. acute dermal toxicity and skin irritation/corrosion), only the DNEL for long-term dermal systemic effects is derived.

No DNEL is derived for oral exposure because no acute toxicity potential was observed up to 5000 mg/kg bw in the acute oral toxicity study

Regarding the hazard for eyes, the substance can be considered as medium hazardous, based on its potential to cause eye damage according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Part E: Risk Characterisation.