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Administrative data

Workers - 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
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
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:
13.9 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

The 28-day oral (gavage) repeated dose study in rats has been chosen (BASF21C0810/89101) for the derivation of DNELs for systemic inhalation effects after long term exposure by route to route extrapolation. A NOEL of 100 mg/kg bw/ day has been observed representing the point of departure. This point of departure is valid to cover all adverse effects observed in an oral (gavage) reproductive/developmental screening test in rats, showing a NOAEL for general, systemic toxicity and a NOAEL for developmental toxicity of 100 mg/kg bw/d (BASF90R0506/09068).  

For the derivation of DNELs for systemic dermal effects after long term exposure, the available dermal reproductive/developmental screening test in rats has been chosen as point of departure, showing a NOAEL for general systemic toxicity, reproductive performance and developmental toxicity above 1000 mg/kg bw/d (BASF82R0506/09C017). 

 

Route to route extrapolation: oral – inhalative:

Due to the lack on route specific information, a default factor of 2 has been applied leading to the assumption, that half of the applied dose is absorbed via the oral route compared to the inhalative route according to current guidance document (R8, ECHA 2008)

 

For the worker, the following DNELs were derived:

 

The NOAEL of the dermal reproductive/developmental screening test in rats was set at 1000 mg/kg bw/d 4-methylanisole.

 

The following assessment factors (AF) were applied:

·       allometric scaling = 4 (according toR8 ECHA 2008)

·       remaining differences = 1 (On the basis of the absence of general adverse systemic effects no difference in sensitivity (toxicodynamic and/or additional toxicokinetic differences) between test animals and humans is to be expected).

·       intraspecies = 3 (based on the absence of substance related adverse effects observed and ECETOC Technical Report No. 86)

·       exposure duration = 6 (subacute to chronic);

·       dose reponse = 1 (according toR8 ECHA 2008)

·       quality of whole database = 1 (based on validity of guideline studies performed).

 

AF = 4 x 1 x 3 x 6 x 1 x 1 = 72. Consequently, the dermal long-term systemic DNEL derived was 13.9 mg/kg bw/d for the worker.

 

For derivation of the long-term systemic inhalative DNEL, the oral NOEL was converted into a corrected inhalative NOAEC of 88 mg/m3 according to the procedure, recommended in the current guidance document (R8, ECHA 2008).

 

NOAEC corrected inhalative = 100*(1/0.38)*(50/100)*(6.7/10) = 88 mg/m3

 

The following assessment factors (AF) were applied:

·       allometric scaling = 1 (not applicable according toR8 ECHA 2008)

·       remaining differences = 1 (On the basis of adverse systemic effects observed, no toxicodynamic and/or further toxicokinetic differences are to be expected between test animals and humans besides the aspects covered in the calculation above and the other assessment factors applied).

·       intraspecies = 5 (according toR8 ECHA 2008);

·       exposure duration = 6 (subacute to chronic);

·       dose reponse = 1 (according toR8 ECHA 2008)

·       quality of whole database = 1 (based on validity of guideline studies performed).

 

AF = 1 x 1 x 5 x 6 x 1 x 1 = 30. Consequently, the inhalative long-term systemic DNEL was set at 2.9 mg/m3 for the worker.

 

For the derivation of DNELs addressing dermal local effects after short term and long term exposure, no quantitative data are available, providing evidence of threshold concentrations for skin irritation in humans. However, data available from secondary source, describing a closed patch test in humans, showed no skin irritation/ sensitization reactions after application of 2% 4-methylanisol in petrolatum (Kligman 1971). Overall, a qualitative risk characterisation including the implementation of suitable risk management measures is performed in the CSR.

 

No DNELs were derived for systemic effects after short term dermal or inhalative exposure, as the substance exhibits no hazardous potential in terms of these endpoints, and the respective long term systemic DNELs are considered sufficient. 

 

No DNELs were derived for local effects after short or long term inhalative exposure, as the substance exhibits no hazardous potential in terms of these endpoints.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEC
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:
8.3 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
120
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:
0.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The 28-day oral (gavage) repeated dose study in rats has been chosen (BASF21C0810/89101) for the derivation of DNELs for systemic oral and inhalation effects after long term exposure by route to route extrapolation. A NOEL of 100 mg/kg bw/ day has been observed representing the point of departure. This point of departure is valid to cover all adverse effects observed in an oral (gavage) reproductive/developmental screening test in rats, showing a NOAEL for general, systemic toxicity and a NOAEL for developmental toxicity of 100 mg/kg bw/d (BASF90R0506/09068).  

For the derivation of DNELs for systemic dermal effects after long term exposure, the available dermal reproductive/developmental screening test in rats has been chosen as point of departure, showing a NOAEL for general systemic toxicity, reproductive performance and developmental toxicity above 1000 mg/kg bw/d (BASF82R0506/09C017).

 

Route to route extrapolation: oral – inhalative:

Due to the lack on route specific information, a default factor of 2 has been applied leading to the assumption, that half of the applied dose is absorbed via the oral route compared to the inhalative route according to current guidance document (R8, ECHA 2008)

 

For the general population, the following DNELs were derived:

 

For derivation of the long-term systemic oral DNEL, the chosen NOEL (100 mg/kg bw/d) was divided by the following assessment factors (AF):

 

·       allometric scaling = 4 (according toR8 ECHA 2008)

·       remaining differences = 1(On the basis of adverse systemic effects observed, no toxicodynamic and/or further toxicokinetic differences are to be expected between test animals and humans besides the aspects covered by the other assessment factors applied).

·       intraspecies = 10 (according toR8 ECHA 2008)

·       exposure duration = 6 (subchronic to chronic);

·       dose reponse = 1 (according toR8 ECHA 2008)

·       quality of whole database = 1 (based on validity of guideline studies performed).

AF = 4 x 1 x 10 x 6 x 1 x 1= 240. Consequently, the oral long-term systemic DNEL derived was 0.4 mg/kg bw/d for the general population.

 

 

The NOAEL of the dermal reproductive/developmental screening test in rats was set at 1000 mg/kg bw/d 4-methylanisole.

 

The following assessment factors (AF) were applied:

·       allometric scaling = 4 (according toR8 ECHA 2008)

·       remaining differences = 1 (On the basis of the absence of general adverse systemic effects no difference in sensitivity (toxicodynamic and/or additional toxicokinetic differences) between test animals and humans is to be expected).

·       intraspecies = 5 (based on the absence of substance related adverse effects observed and ECETOC Technical Report No. 86)

·       exposure duration = 6 (subacute to chronic);

·       dose reponse = 1 (according toR8 ECHA 2008)

·       quality of whole database = 1 (based on validity of guideline studies performed).

 

AF = 4 x 1 x 5 x 6 x 1 x 1 = 120. Consequently, the dermal long-term systemic DNEL derived was 8.3 mg/kg bw/d for the population.

 

For derivation of the long-term systemic inhalative DNEL, the oral NOEL was converted into a corrected inhalative NOAEC of 43 mg/m3 according to the procedure, recommended in the current guidance document (R8, ECHA 2008).

 

NOAEC corrected inhalative = 100*(1/1.15)*(50/100)= 43 mg/m3

 

The following assessment factors (AF) were applied:

·       allometric scaling = 1 (not applicable according toR8 ECHA 2008)

·       remaining differences = 1 (On the basis of adverse systemic effects observed, no toxicodynamic and/or further toxicokinetic differences are to be expected between test animals and humans besides the aspects covered in the calculation above and the other assessment factors applied).

·       intraspecies = 10 (according toR8 ECHA 2008);

·       exposure duration = 6 (subacute to chronic);

·       dose reponse = 1 (according toR8 ECHA 2008)

·       quality of whole database = 1 (based on validity of guideline studies performed).

 

AF = 1 x 1 x 10 x 6 x 1 x 1 = 60. Consequently, the inhalative long-term systemic DNEL was set at 0.7 mg/m3 for the general population.

 

For the derivation of DNELs addressing dermal local effects after short term and long term exposure, no quantitative data are available, providing evidence of threshold concentrations for skin irritation in humans. However, data available from secondary source, describing a closed patch test in humans, showed no skin irritation/ sensitization reactions after application of 2% 4-methylanisol in petrolatum (Kligman 1971). Overall, a qualitative risk characterisation including the implementation of suitable risk management measures is performed in the CSR.

 

No DNELs were derived for systemic effects after short term oral exposure, since the respective long term DNEL is considered sufficient to ensure the absence of acute toxic effects.

 

 

 

No DNELs were derived for systemic effects after short term dermal or inhalative exposure, as the substance exhibits no hazardous potential in terms of these endpoints, and the respective long term systemic DNELs are considered sufficient. 

 

No DNELs were derived for local effects after short or long term inhalative exposure, as the substance exhibits no hazardous potential in terms of these endpoints.