Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL

Workers - Hazard for the eyes

Additional information - workers

The data discussed in this section were derived from toxicity studies with the hydrochloride of the same azo dye (read-across to Basisch Gelb 8511, CAS 118208-02-9).

The test substance is severely irritating to the eye as determined in an OECD TG 405 study at 0.1 ml bulk volume per rabbit eye (BASF AG, 1990). Since eye irritation is a qualitative endpoint, a DNEL for eye irritation is not quantifiable. However, on account of the eye irritating effect of the test substance and of the highly accepted use of suitable protective equipment it can be assumed that for workers, as a rule, eye contact is avoided by using suitable personal protective equipment.

Due to the toxicological profile and the physico-chemical properties of the test substance, only the dermal route is a relevant route of exposure for human workers. Therefore, the dermal DNELs for systemic effects derived from an acute dermal toxicity study in rats and a long-term oral repeated dose study in rats are considered sufficient to ensure the safety of human workers.

1) Dermal DNEL - acute/short-term exposure:

The dermal DNEL for acute/short-term exposure was derived based on the LD0 value from an acute dermal toxicity study with rats (BASF AG, 1990). In this study, no mortality and no clinical signs were observed after the dermal administration of Basisch Gelb 8511 to rats under semiocclusive conditions at 2000 mg/kg. Furthermore, no pathological findings were noted at gross pathology. According to this study, the dermal LD0 (= NOAEL for sub-lethal effects) of the test substance is considered to be equal to or greater than 2000 mg/kg. This value was identified as the correct starting point for the derivation of the DNEL after acute/short-term exposure.

The following assessment factors (AF) were applied to the correct starting point:

Interspecies variation:

An allometric scaling factor of 4 for interspecies extrapolation was recognised due to the larger exposure-related dermal area in humans compared to rats. Since no systemic toxicity was observed in this study and is not expected to occur in humans after dermal exposure due to the low dermal absorption of the test substance, no additional assessment factor for remaining differences in interspecies variation was applied.

 

Intraspecies variation:

The intraspecies variation among human workers was recognised by an assessment factor of 5 by default.

 

Exposure duration:

An assessment factor of 1 was used for extrapolation of exposure duration from the acute animal study to acute/short-term human exposure.

 

Accordingly, an overall assessment factor of 20 was calculated based on the recommendations given in the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-6, p. 38) and based on the above mentioned arguments. Thus, the dermal DNEL for acute/short-term exposure was calculated as follows:

Dermal DNEL acute/short-term exposure – systemic effects = dermal LD0 / Overall AF = 2000 mg/kg body weight / 20 = 100 mg/kg body weight.

2) Dermal DNEL - long-term exposure:

The dermal DNEL for long-term exposure was derived based on the NOAEL value from a subchronic repeated oral dose study with rats (BASF AG, 1991). In this study, the oral administration of Basisch Gelb 8511 to rats caused lethality at 180/120 mg/kg body weight due to chronic tympania. Toxicity was further characterized by mild neutrophilia in both sexes indicating a slight inflammatory reaction. Discoloration of urine and/or feces was seen in all treatment groups. This was, however, related to the physical properties of the test compound (dye stuff) but does not represent a toxicologically relevant effect. The affection of the respiratory system (respiratory sounds) is probably due to an unintentional aspiration of the test substance as a consequence of attempts to vomit the test substance. It may therefore be addressed as a substance-related effect, but not an adverse effect. The NOEL was 10 mg/kg body weight in males, but below 10 mg/kg body weight in females based on the observed affection of the respiratory system in one female. The respective NOAEL was 10 mg/kg body weight in both sexes.

 

The NOAEL of 10 mg/kg body weight which was taken as relevant dose descriptor for systemic effects after long-term exposure had to be modified in order to get the correct starting point for dermal DNEL derivation:

In the first step, a route-to-route extrapolation within the species rat was performed. The oral rat NOAEL was converted into the dermal rat NOAEL corrected for differences between oral absorption (assumed to be 50%, as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 25) and dermal absorption (1.25%, as determined in a dermal absorption study in rats (BASF AG, 1999)) by multiplying with the corresponding factor (x 50%/1.25%). The resulting corrected starting point for dermal DNEL derivation is equal to 400 mg/kg body weight.

The following assessment factors (AF) were applied to the correct starting point:

Interspecies variation:

An allometric scaling factor of 4 for interspecies extrapolation was recognised due to the larger exposure-related dermal area in humans compared to rats. Since chronic tympania was the relevant adverse clinical finding in this study, and tympania can result in lethality specifically in rodents like the rat but is not an adverse effect in humans, no additional assessment factor for remaining differences in interspecies variation was applied.

 

Intraspecies variation:

The intraspecies variation among human workers was recognised by an assessment factor of 5 by default.

 

Exposure duration:

An assessment factor of 2 was used for extrapolation of exposure duration from sub-chronic (90-day study) to chronic by default.

 

Accordingly, an overall assessment factor of 40 was calculated based on the recommendations given in the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-6, p. 38) and based on the above mentioned arguments. Thus, the dermal DNEL for long-term exposure was calculated as follows:

Dermal DNEL long-term exposure – systemic effects = corrected dermal NOAEL / Overall AF = 400 mg/kg body weight / 40 = 10 mg/kg body weight.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Additional information - General Population

The data discussed in this section were derived from toxicity studies with the hydrochloride of the same azo dye (read-across to Basisch Gelb 8511, CAS 118208-02-9).

Concerning the general population, the dermal and oral routes seem to be the most appropriate routes based on a possible exposure and on the results of the toxicity studies. Therefore, the dermal and oral DNELs for systemic effects derived from a long-term oral repeated dose study in rats are considered sufficient to ensure the safety of the general population.

1) Dermal DNEL - acute/short-term exposure:

The dermal DNEL for acute/short-term exposure was derived based on the LD0 value from an acute dermal toxicity study with rats (BASF AG, 1990). In this study, no mortality and no clinical signs were observed after the dermal administration of Basisch Gelb 8511 to rats under semiocclusive conditions at 2000 mg/kg. Furthermore, no pathological findings were noted at gross pathology. According to this study, the dermal LD0 (= NOAEL for sub-lethal effects) of the test substance is considered to be equal to or greater than 2000 mg/kg. This value was identified as the correct starting point for the derivation of the DNEL after acute/short-term exposure.

The following assessment factors (AF) were applied to the correct starting point:

Interspecies variation:

An allometric scaling factor of 4 for interspecies extrapolation was recognised due to the larger exposure-related dermal area in humans compared to rats. Since no systemic toxicity was observed in this study and is not expected to occur in humans after dermal exposure due to the low dermal absorption of the test substance, no additional assessment factor for remaining differences in interspecies variation was applied.

 

Intraspecies variation:

The intraspecies variation among human workers was recognised by an assessment factor of 10 by default.

 

Exposure duration:

An assessment factor of 1 was used for extrapolation of exposure duration from the acute animal study to acute/short-term human exposure.

 

Accordingly, an overall assessment factor of 40 was calculated based on the recommendations given in the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-6, p. 38) and based on the above mentioned arguments. Thus, the dermal DNEL for acute/short-term exposure was calculated as follows:

Dermal DNEL acute/short-term exposure – systemic effects = dermal LD0 / Overall AF = 2000 mg/kg body weight / 40 = 50 mg/kg body weight.

2) Dermal DNEL - long-term exposure:

The dermal DNEL for long-term exposure was derived based on the NOAEL value from a subchronic repeated oral dose study with rats (BASF AG, 1991). In this study, the oral administration of Basisch Gelb 8511 to rats caused lethality at 180/120 mg/kg body weight due to chronic tympania. Toxicity was further characterized by mild neutrophilia in both sexes indicating a slight inflammatory reaction. Discoloration of urine and/or feces was seen in all treatment groups. This was, however, related to the physical properties of the test compound (dye stuff) but does not represent a toxicologically relevant effect. The affection of the respiratory system (respiratory sounds) is probably due to an unintentional aspiration of the test substance as a consequence of attempts to vomit the test substance. It may therefore be addressed as a substance-related effect, but not an adverse effect. The NOEL was 10 mg/kg body weight in males, but below 10 mg/kg body weight in females based on the observed affection of the respiratory system in one female. The respective NOAEL was 10 mg/kg body weight in both sexes.

 

The NOAEL of 10 mg/kg body weight which was taken as relevant dose descriptor for systemic effects after long-term exposure had to be modified in order to get the correct starting point for dermal DNEL derivation:

In the first step, a route-to-route extrapolation within the species rat was performed. The oral rat NOAEL was converted into the dermal rat NOAEL corrected for differences between oral absorption (assumed to be 50%, as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 25) and dermal absorption (1.25%, as determined in a dermal absorption study in rats (BASF AG, 1999)) by multiplying with the corresponding factor (x 50%/1.25%).

The resulting corrected starting point for dermal DNEL derivation is equal to 400 mg/kg body weight.

The following assessment factors (AF) were applied to the correct starting point:

Interspecies variation:

An allometric scaling factor of 4 for interspecies extrapolation was recognised due to the larger exposure-related dermal area in humans compared to rats. Since chronic tympania was the relevant adverse clinical finding in this study, and tympania can result in lethality specifically in rodents like the rat but is not an adverse effect in humans, no additional assessment factor for remaining differences in interspecies variation was applied.

 

Intraspecies variation:

The intraspecies variation among human workers was recognised by an assessment factor of 10 by default.

 

Exposure duration:

An assessment factor of 2 was used for extrapolation of exposure duration from sub-chronic (90-day study) to chronic by default.

 

Accordingly, an overall assessment factor of 80 was calculated based on the recommendations given in the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-6, p. 38) and based on the above mentioned arguments. Thus, the DNEL for long-term exposure was calculated as follows:

Dermal DNEL long-term exposure – systemic effects = corrected dermal NOAEL / Overall AF = 400 mg/kg body weight / 80 = 5 mg/kg body weight.

3) Oral DNEL:

The oral DNEL for long-term exposure was derived based on the NOAEL value from a subchronic oral repeated dose study with rats (BASF AG, 1991). In this study, the oral administration of Basisch Gelb 8511 caused lethality at 180/120 mg/kg body weight due to chronic tympania. Toxicity was further characterized by mild neutrophilia in both sexes indicating a slight inflammatory reaction. Discoloration of urine and/or feces was seen in all treatment groups. This was, however, related to the physical properties of the test compound (dye stuff) but does not represent a toxicologically relevant effect. The affection of the respiratory system (respiratory sounds) is probably due to an unintentional aspiration of the test substance as a consequence of attempts to vomit the test substance. It may therefore be addressed as a substance-related effect, but not an adverse effect. The NOEL was 10 mg/kg body weight in males, but below 10 mg/kg body weight in females based on the observed affection of the respiratory system in one female. The respective NOAEL was 10 mg/kg body weight in both sexes.

 

Consequently, the NOAEL of 10 mg/kg body weight which was taken as relevant dose descriptor for systemic effects after long-term exposure was identified as the correct starting point for oral DNEL derivation.

The following assessment factors (AF) were applied to the correct starting point:

Interspecies variation:

Since chronic tympania was the relevant adverse clinical finding in this study, and tympania can result in lethality specifically in rodents like the rat but is not an adverse effect in humans, the assessment factor for interspecies variation was set to be 1.

 

Intraspecies variation:

The intraspecies variation among the general population was recognised by an assessment factor of 10 by default.

 

Exposure duration:

An assessment factor of 2 was used for extrapolation of exposure duration from sub-chronic (90-day study) to chronic by default.

 

Accordingly, an overall assessment factor of 20 was calculated based on the recommendations given in the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-6, p. 38) and based on the above mentioned arguments. Thus, the oral DNEL for long-term exposure was calculated as follows:

Oral DNEL long-term exposure – systemic effects = oral NOAEL / Overall AF = 10 mg/kg body weight / 20 = 0.5 mg/kg body weight.