7-anilino-4-hydroxy-3-[[6-methoxy-4-[(6-sulpho-2,4-xylyl)azo]-m-tolyl]azo]naphthalene-2-sulphonic acid, sodium salt, compound with 2,2',2''-nitrilotriethanol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.263 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:

15 mg/kg bw/day

Modified dose descriptor starting point:

other: NAEC

Value:

18.375 mg/m³

Explanation for the modification of the dose descriptor starting point:

No infromation on Direct Violet 051 is vailable in order to derive DNEL value. For this reason data on Similar Substance 01 have been taken into account.

No long-term exposure data is available for the inhalation route, therefore, the NOAEL resulted from an animal study after an oral administration of the substance for at least 28 days to rats, is used. Route-to route extrapolation is therefore needed from the oral to the inhalation route. The most sensitive value was found in the Reproductive/Developmental Screening Test combined with Repeated Dose Toxicity test.

The NOAEL value was calculated to be 15 mg/kg bw/day, as at the higher dose (40 mg/kg bw) toxic effects were observed on testes.

To calculate the DNEL it is necessary first to calculate the NAECworkers, inhalation applying the following formula:

NAECworkers, inhalation= NOAELrat, oral÷ 4 × 70 kg ÷ 10 m3× 1.4 × 0.5 = 15 mg/kg bw/day ÷ 4 × 70 kg ÷ 10 m3× 1.4 × 0.5 = 18.375 mg/m3

As the NOAEL value was particular to rats, an assessment factor of 4 was considered for interspecies differences; the standard body weight considered for workers is 70 kg, therefore, the NOAEL is multiplied by a factor of 70 kg. A worker is considered to be exposed to 10 m3 for 8 hours per day for 5 days out of 7, therefore, the NOAEL value is multiplied by 10 m3 and a factor of 1.4 to account for weekends.

Finally, absorption of a substance by the inhalation route is considered to be 100 % once it reaches the alveolar level, whereas absorption via the oral route is considered generically to be 50 %, therefore, the NOAEL value is multiplied by 0.5 to account for absorption differences.

The DNELworkers was then calculated as follows:

DNELworkers, inhalation = NAECworkers,inhalation/Overall AF = 18.375 mg/m3 / 75 = 0.2625 mg/m3

The overall assessment factors (AF) is calculated multiplying the AFs detailed below.

AF for dose response relationship:

1

Justification:

AF for dose response relationship is considered 1 as the source study uses a NOAEL

AF for differences in duration of exposure:

6

Justification:

AF for differences in duration of exposure is considered 6 as the source study is a sub-acute toxicity study (63-day reproductive/developmental screening combined with repeated dose toxicity; OECD 422)

AF for interspecies differences (allometric scaling):

1

Justification:

Interspecies differences are already considered in the original formula (above), whereby the NOAEL was multiplied by a factor of 4 to allow for differences between rats and humans

AF for other interspecies differences:

2.5

Justification:

Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)

AF for intraspecies differences:

5

Justification:

AF for intraspecies differences is considered 5 to allow for potential differences in the population of workers

AF for the quality of the whole database:

1

Justification:

Good standard of quality of database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.7 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):

300

Dose descriptor starting point:

NOAEL

Value:

15 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

210 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No information on Direct Violet 051 is vailable in order to derive DNEL value. For this reason data on Similar Substance 01 have been taken into account.

No long-term exposure data is available for the inhalation route, therefore, the NOAEL resulted from an animal study after an oral administration of the substance for at least 28 days to rats, is used. Route-to route extrapolation is therefore needed from the oral to the inhalation route. The most sensitive value was found in the Reproductive/Developmental Screening Test combined with Repeated Dose Toxicity test.

The NOAEL value was calculated to be 15 mg/kg bw/day, as at the higher dose (40 mg/kg bw) toxic effects were observed on testes.

To calculate the DNEL it is necessary first to calculate the NAECworkers, dermal applying the following formula:

NOAELworkers, dermal= NOAELrat, oral x 1.4/0.1 = 15 mg/kg bw/day × 1.4/0.1 = 210 mg/kg bw

A worker is considered to be exposed to a substance for 5 days out of 7, therefore, the NOAEL value is multiplied by a factor of 1.4.

A default value of 100 % skin absorption is allocated to substances with a molar mass below 500 and a partition coefficient between log Pow-1 and 4. In the case of Direct Violet 051 the molecular mass and/or partition coefficient values are outside the given range, therefore a skin absorption value of 10 % is allocated.

The DNELworkers, dermal was then calculated as follows:

DNELworkers, dermal= NOAECworkers,dermal/Overall AF = 210 mg/kg bw/ 300 = 0.7 mg/kg bw

The overall assessment factors (AF) is calculated multiplying the AFs detailed below.

AF for dose response relationship:

1

Justification:

AF for dose response relationship is considered 1 as the source study uses a NOAEL

AF for differences in duration of exposure:

6

Justification:

AF for differences in duration of exposure is considered 6 as the source study is a sub-acute toxicity study (63-day reproductive/developmental screening combined with repeated dose toxicity; OECD 422)

AF for interspecies differences (allometric scaling):

4

Justification:

An AF value of 4 is provided for interspecies differences between the rat and human

AF for other interspecies differences:

2.5

Justification:

Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)

AF for intraspecies differences:

5

Justification:

AF for intraspecies differences is considered 5 to allow for potential differences in the population of workers

AF for the quality of the whole database:

1

Justification:

Good standard of quality of database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.037 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:

15 mg/m³

Modified dose descriptor starting point:

other: NAEC

Value:

5.625 mg/m³

Explanation for the modification of the dose descriptor starting point:

No information on Direct Violet 051 is available in order to derive DNEL value. For this reason data on Similar Substance 01 have been taken into account.

No long-term exposure data is available for the inhalation route, therefore, the NOAEL resulted from an animal study after an oral administration of the substance for at least 28 days to rats, is used. Route-to route extrapolation is therefore needed from the oral to the inhalation route. The most sensitive value was found in the Reproductive/Developmental Screening Test combined with Repeated Dose Toxicity test.

The NOAEL value was calculated to be 15 mg/kg bw/day, as at the higher dose (40 mg/kg bw) toxic effects were observed on testes.

To calculate the DNEL it is necessary first to calculate the NAEChuman, inhalation applying the following formula:

NAEChuman, inhalation= NOAELrat, oral÷ 4 × 60 kg ÷ 20 m3× 0.5 = 15 mg/kg bw/day ÷ 4 × 60 kg ÷ 20 m3× 0.5 = 5.625 mg/m3

As the NOAEL value was particular to rats,an assessment factor of 4 was considered for interspecies differences; the standard body weight considered for the general population is 60 kg, therefore, the NOAEL is multiplied by a factor of 60 kg. A person is considered to be exposed to 20 m3 for 24 hours per day for 7 days a week, therefore, the NOAEL value is multiplied by 20 m3. Finally, absorption of a substance by the inhalation route is considered to be 100 % once it reaches the alveolar level, whereas absorption via the oral route is considered generically to be 50 %, therefore, the NOAEL value is multiplied by 0.5 to account for absorption differences.

The DNELhumans was then calculated as follows:

DNELhumans, inhalation= NAEChumans,inhalation/Overall AF = 5.625 mg/m3/ 150 = 0.0375 mg/m3

The overall assessment factors (AF) is calculated multiplying the AFs detailed below.

AF for dose response relationship:

1

Justification:

AF for dose response relationship is considered 1 as the source study uses a NOAEL

AF for differences in duration of exposure:

6

Justification:

AF for differences in duration of exposure is considered 6 as the source study is a sub-acute toxicity study (63-day reproductive/developmental screening combined with repeated dose toxicity; OECD 422)

AF for interspecies differences (allometric scaling):

1

Justification:

Interspecies differences are already considered in the original formula (above), whereby the NOAEL was multiplied by a factor of 4 to allow for differences between rats and humans

AF for other interspecies differences:

2.5

Justification:

Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)

AF for intraspecies differences:

10

Justification:

AF for intraspecies differences is considered 10 to allow for potential differences in the general population such as age, health, race

AF for the quality of the whole database:

1

Justification:

Good standard quality data base

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.25 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:

15 mg/kg bw/day

Modified dose descriptor starting point:

other: NOAEL dermal

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No information on Direct Violet 051 is available in order to derive DNEL value. For this reason data on Similar Substance 01 have been taken into account.

No long-term exposure data is available for the inhalation route, therefore, the NOAEL resulted from an animal study after an oral administration of the substance for at least 28 days to rats, is used. Route-to route extrapolation is therefore needed from the oral to the inhalation route. The most sensitive value was found in the Reproductive/Developmental Screening Test combined with Repeated Dose Toxicity test.

The NOAEL value was calculated to be 15 mg/kg bw/day, as at the higher dose (40 mg/kg bw) toxic effects were observed on testes.

To calculate the DNEL it is necessary first to calculate the NOAELhuman, dermal applying the following formula:

NOAELhuman, dermal= NOAELrat, oral/ 0.1 = 15 mg/kg bw/day / 0.1 = 150 mg/kg bw

A default value of 100 % skin absorption is allocated to substances with a molar mass below 500 and a partition coefficient between log Pow-1 and 4. In the case of Direct Violet 051 the molecular mass and/or partition coefficient values are outside the given range, therefore a skin absorption value of 10 % is allocated.

The DNELhumans, dermalwas then calculated as follows:

DNELhumans, dermal= NOAEChumans,dermal/Overall AF = 150 mg/kg bw/ 600 = 0.25 mg/kg bw

The overall assessment factors (AF) is calculated multiplying the AFs detailed below.

AF for dose response relationship:

1

Justification:

AF for dose response relationship is considered 1 as the source study uses a NOAEL

AF for differences in duration of exposure:

6

Justification:

AF for differences in duration of exposure is considered 6 as the source study is a sub-acute toxicity study (63-day reproductive/developmental screening combined with repeated dose toxicity; OECD 422)

AF for interspecies differences (allometric scaling):

4

Justification:

An AF value of 4 is provided for interspecies differences between the rat and human

AF for other interspecies differences:

2.5

Justification:

Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)

AF for intraspecies differences:

10

Justification:

AF for intraspecies differences is considered 10 to allow for potential differences in the general population

AF for the quality of the whole database:

1

Justification:

Good standard quality of database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.025 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:

15 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No information on Direct Violet 051 is vailable in order to derive DNEL value. For this reason data on Similar Substance 01 have been taken into account.

No long-term exposure data is available for the inhalation route, therefore, the NOAEL resulted from an animal study after an oral administration of the substance for at least 28 days to rats, is used. Route-to route extrapolation is therefore needed from the oral to the inhalation route. The most sensitive value was found in the Reproductive/Developmental Screening Test combined with Repeated Dose Toxicity test.

The NOAEL value is considered 15 mg/kg bw/day.

The overall assessment factors (AF) is calculated multiplying the AFs detailed below.

AF for dose response relationship:

1

Justification:

AF for dose response relationship is considered 1 as the source study uses a NOAEL

AF for differences in duration of exposure:

6

Justification:

AF for differences in duration of exposure is considered 6 as the source study is a sub-acute toxicity study (63-day reproductive/developmental screening combined with repeated dose toxicity; OECD 422)

AF for interspecies differences (allometric scaling):

4

Justification:

An AF value of 4 is provided for interspecies differences between the rat and human

AF for other interspecies differences:

2.5

Justification:

Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences)

AF for intraspecies differences:

10

Justification:

AF for intraspecies differences is considered 10 to allow for potential differences in the general population

AF for the quality of the whole database:

1

Justification:

Good/standard quality database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)