Trisodium bis[(3'-nitro-5'-sulfonato-(6-amino-2-[4-(2-hydroxy-1-naphtylazo)phenylsulfonylamino]pyrimidin-5-azo)benzene-2',4-diolato)]chromate(III)

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:

other: NAEC

Value:

176.32 mg/m³

Explanation for the modification of the dose descriptor starting point:

NOAEL from oral repeated dose toxicity study (28 days) in rats was selected as the most representative starting dose based on: 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) and 8 h- workers (10 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 worker = 200 mg/kg bw/d / (0.38 m³/kg bw) × (6.7 m³/10 m³ (8h)) × 0.5

AF for dose response relationship:

1

Justification:

NOAEL used for NAEC derivation

AF for differences in duration of exposure:

6

Justification:

subacute (28 d) 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

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:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Route of original study:

Dermal

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

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:

no hazard identified

Additional information - workers

HAZARD VIA INHALATION ROUTE

Systemic effects long term exposure

No experimental evidence of absorption via inhalation is available, however a DNEL is computed mainly considering that the substance is a powder with MMD of 3.1 µm.

Absorption may occur via the respiratory tract as well as via the gastrointestinal tract if inhaled particles are swallowed.

For DNEL calculation, NOAEL from oral repeated dose toxicity study (28 days) in rats was selected as the most representative starting dose based on: 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) and 8 h- workers (10 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 for worker = 200 mg/kg bw/d / (0.38 m³/kg bw) × (6.7 m³/10 m³(8h)) × 0.5 = 176.32 mg/m³

An overall assessment factor of 75 to be applied is calculated considering AF for dose response relationship 1 (NOAEL used for NAEC derivation), AF for difference in duration of exposure 6 (subacute (28 d) to chronic), AF for interspecies differences 1 (allometric scaling has been already considered in starting point derivation), AF for other interspecies differences 2.5 (toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)), AF for intraspecies differences 5 (workers), AF for quality of the whole database 1 (good quality of available data) and AF for remaining uncertainties 1 (no significant uncertainties remaining).

Therefore, DNEL is calculated: 176.32 mg/m³ / 75 = 2.35 mg/m³.

Systemic effects short term exposure

According to “ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health”, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Since the substance is not classified for acute toxicity, no DNEL derivation is necessary and no hazard is identified.

Local effects long and short term exposures

Since no inhalation test was performed, no local effect could be observed. However, since the substance is non irritant to eye, an effect on mucous is not expected and no hazard is idenfied.

HAZARD VIA DERMAL ROUTE

Systemic effects long and short term exposure

The substance is classified as Skin Sensitizer sub-category 1B according to the CLP Regulation (EC 1272/2008). According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation” medium hazard is associated to the substance.

Local effects long and short term exposures

As no skin irritation was observed in short term studies (i.e. acute dermal toxicity and skin irritation/corrosion), local effects for dermal route during both short and long term exposure are not expected.

HAZARD TO THE EYE

As the available test showed that the substance is not irritant to eye, no hazard is identified.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.58 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:

other: NAEC

Value:

86.96 mg/m³

Explanation for the modification of the dose descriptor starting point:

NOAEL from oral repeated dose toxicity study (28 days) in rats was selected as the most representative starting dose based on: 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 = 200 mg/kg bw/d / (1.15 m³/kg bw) × 0.5 = 86.96 mg/m³

AF for dose response relationship:

1

Justification:

NOAEL used for NAEC derivation

AF for differences in duration of exposure:

6

Justification:

subacute (28 d) 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

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

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Route of original study:

Dermal

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Route of original study:

Dermal

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:

0.33 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

Explanation for the modification of the dose descriptor starting point:

No extrapolation is necessary as NOAEL from oral repeated dose toxicity study (28 days) in rats 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:

NOEL used for NAEC derivation

AF for differences in duration of exposure:

6

Justification:

subacute (28 d) 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

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

HAZARD VIA INHALATION ROUTE

Systemic effects long term exposure

No experimental evidence of absorption via inhalation is available, however a DNEL is computed mainly considering that the substance is a powder with MMD of 3.1 µm.

Absorption may occur via the respiratory tract as well as via the gastrointestinal tract if inhaled particles are swallowed.

For DNEL calculation, NOAEL from oral repeated dose toxicity study (28 days) in rats was selected as the most representative starting dose based on: 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 = 200 mg/kg bw/d / (1.15 m³/kg bw) × 0.5 = 86.96 mg/m³

An overall assessment factor of 150 to be applied is calculated considering AF for dose response relationship 1 (NOAEL used for NAEC derivation), AF for difference in duration of exposure 6 (subacute (28 d) to chronic), AF for interspecies differences 1 (allometric scaling has been already considered in starting point derivation), AF for other interspecies differences 2.5 (toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)), AF for intraspecies differences 10 (general population), AF for quality of the whole database 1 (good quality of available data) and AF for remaining uncertainties 1 (no significant uncertainties remaining).

Therefore, DNEL is calculated: 86.96 mg/m³ / 150 = 0.58.

Systemic effects short term exposure

According to “ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health”, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Since the substance is not classified for acute toxicity, no DNEL derivation is necessary andno hazard is identified.

Local effects long and short term exposures

Since no inhalation test was performed, no local effect could be observed. However, since the substance is non irritant to eye, an effect on mucous is not expected and no hazard is idenfied.

HAZARD VIA DERMAL ROUTE

Systemic effects long and short term exposures

The substance is classified as Skin Sensitizer sub-category 1B according to the CLP Regulation (EC 1272/2008). According to “ECHA Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation” medium hazard is associated to the substance.

Local effects long and short term exposures

As no skin irritation was observed in short term studies (i.e. acute dermal toxicity and skin irritation/corrosion), local effects for dermal route in long and short exposure are not expected.

HAZARD VIA ORAL ROUTE

Systemic effects long term exposure

For DNEL calculation, NOAEL from oral repeated dose toxicity study (28 days) in rats was selected as the most representative starting dose based on: study duration, presence of adverse effects, parameters observed.

An overall assessment factor of 600 to be applied is calculated considering AF for dose response relationship 1 (NOAEL used for NAEC derivation), AF for difference in duration of exposure 6 (subacute (28 d) to chronic), AF for interspecies differences 4 ( rats were used in the available test), AF for other interspecies differences 2.5 (toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)), AF for intraspecies differences 10 (general population), AF for quality of the whole database 1 (good quality of available data) and AF for remaining uncertainties 1 (no significant uncertainties remaining).

Therefore, DNEL is calculated: 200 mg/kg bw / 600 = 0.33.

Systemic effects short term exposure

According to “ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health”, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Since the substance is not classified for acute toxicity, no DNEL derivation is necessary.

HAZARD TO THE EYE

As the available test showed that the substance is not irritant to eye, no hazard is identified.