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A mixture of isomers of: 1,1'-[(3,5(or 2,4 or 4,6 or 2,6)-dihydroxy-o(or m or p)-phenylene)bis(azo-meta-phenyleneazo{1-[3-(dimethylamino)propyl]-1,2-dihydro-6-hydroxy-4-methyl-2-oxopyridine-5,3-diyl})]dipyridinium-dichloride-dihydrochloride; 1-(1-[3-(dimethylamino)propyl]-5-{3-[x-(4-{1-[3-(dimethylamino)propyl]-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-5-pyridinio-3-pyridylazo}phenylazo)-2,4(or 2,6 or 3,5 or 4,6)-dihydroxyphenylazo]phenylazo}-1,2-dihydro-6-hydroxy-4-methyl-2-oxo-3-pyridyl)pyridinium-dichloride-dihydrochloride (where x is variable)
EC number: 404-540-1 | CAS number: 159405-95-5 BRAUN HM 2763; BROWN HM 2763; BRUN HM 2763; BRUNO HM 2763
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 16.46 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:
- 1 234.21 mg/m³
- Explanation for the modification of the dose descriptor starting point:
8-h breathing volume of rat (0.38 m3/kg) and 8-h breathing volume of human (6.7 m3/kg in general population and 10 m3/kg in worker); days per week of exposure in
experimental animals (7 d/w) and in humans (5 d/w in workers).
No experimental data on absorption via oral and inhalation route available, thus worst case assumption for absorption: 50 % orally and 100 % by inhalation.Corrected inhalatory NOAEC = 1000 mg/kg bw/day × (1/0.38 m3/kg/day) × (50 %/100 %) × (6.7 m3 (8h)/10 m3 (8h)) × (7 d/w / 5 d/w) = 1234.21 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- not required, starting point is NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from subacute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- implicitly included in the corrected starting point
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor for remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- default factor for worker
- AF for the quality of the whole database:
- 1
- Justification:
- not required
- AF for remaining uncertainties:
- 1
- Justification:
- not required
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:
- medium hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
- Route of original study:
- Dermal
Acute/short term exposure
- Hazard assessment conclusion:
- high 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:
- medium hazard (no threshold derived)
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
Inhalation route - systemic effects
A DNEL for prolonged exposure was derived from the oral subacute study, which revealed a NOAEL = 1000 mg/kg bw/day (no LOAEL determined, substance not classified as to repeated dose toxicity properties).
No hazard was identified upon short-term exposure, since the substance was not classified as acutely toxic.
Inhalation route - local effects
Local effects by long-term and short-term inhalation were assessed, based on a eye irritation study, as no study by via inhalation was available. Medium and low hazard were identified due to uncertainties by exposure route and duration.
Dermal route - systemic effects
Absorption by dermal route is expected to be low, based on a high molecular weight and a low logPow of the substance. However, a positive response in the GPMT gave evidence of absorption to a certain extent.
Accordingly, both long-term and short-term exposure to test substance via dermal route was associated to a high hazard, as might cause hypersensitivity reactions.
Dermal route - local effects
In a skin irritation test, slight reversible irritation was seen, not leading to classification. Consequently, no hazard was identified for acute exposure by dermal route.
However, slight irritation signs were noted in the acute toxicity test, in the skin irritation test and in the preliminary screenings in the GPMT. As no data was available on possible effects upon prolonged exposure, a medium hazard was assumed.
No hazard for eyes was identified as the substance is not eye irritant.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.9 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:
- 434.78 mg/m³
- Explanation for the modification of the dose descriptor starting point:
No inhalation study is available and the NOAEC was derived by route to route extrapolation from the oral NOAEL.
24 h exposure time, extrapolation from 50 % bioavailability oral to 100 % bioavailability inhalation.
Corrected inhalatory NOAEC = 1000 mg/kg bw/day × (1/1.15 m3/kg/day) × (50 %/100 %) = 434.78 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- not required, starting point is NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from subacute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not for concentrations
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor for remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- default factor for general population
- AF for the quality of the whole database:
- 1
- Justification:
- not required
- AF for remaining uncertainties:
- 1
- Justification:
- not required
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:
- medium hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
- Route of original study:
- Dermal
Acute/short term exposure
- Hazard assessment conclusion:
- high 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:
- medium hazard (no threshold derived)
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:
- 1.67 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):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route-to-route extrapolation performed.
- AF for dose response relationship:
- 1
- Justification:
- not required, starting point is NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from subacute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- allometric scaling factor rat-human
- AF for other interspecies differences:
- 2.5
- Justification:
- default factor for remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- default factor for general population
- AF for the quality of the whole database:
- 1
- Justification:
- not required
- AF for remaining uncertainties:
- 1
- Justification:
- not required
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:
- no hazard identified
Additional information - General Population
Inhalation route - systemic effects
A DNEL for prolonged exposure was derived from the oral subacute study, which revealed a NOAEL = 1000 mg/kg bw/day (no LOAEL determined, substance not classified as to repeated dose toxicity properties).
No hazard was identified upon short-term exposure, since the substance was not classified as acutely toxic.
Inhalation route - local effects
Local effects by long-term and short-term inhalation were assessed, based on a eye irritation study, as no study via inhalation was available. Medium and low hazard were identified due to uncertainties by exposure route and duration.
Dermal route - systemic effects
Absorption by dermal route is expected to be low, based on a high molecular weight and a low logPow of the substance. However, a positive response in the GPMT gave evidence of absorption to a certain extent.
Accordingly, both long-term and short-term exposure to test substance via dermal route was associated to a high hazard, as might cause hypersensitivity reactions.
Dermal route - local effects
In a skin irritation test, slight reversible irritation was seen, not leading to classification. Consequently, no hazard was identified for acute exposure by dermal route.
However, slight irritation signs were noted in the acute toxicity test, in the skin irritation test and in the preliminary screenings in the GPMT. As no data was available on possible effects upon prolonged exposure, a medium hazard was assumed.
Oral route - systemic effects
A DNEL for prolonged exposure was derived from the oral subacute study, which revealed a NOAEL = 1000 mg/kg bw/day (no LOAEL determined, substance not classified as to repeated dose toxicity properties).
No hazard was identified upon short-term exposure, since the substance was not classified as acutely toxic.
No hazard for eyes was identified as the substance is not eye irritant.
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