Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
3.25 mg/m³
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:
DMEL (Derived Minimum Effect Level)
Value:
234 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Long-term - systemic - inhalation

Hazard assessment of the target substance is based on the most hazardous and critical constituent, benzene.

In accordance with REACH guidance (Appendix R.8-13), a science-based Binding Occupational Exposure Limit value (BOELV) can be used in place of a formal DN(M)EL provided no new scientific information exists which challenges the validity of the BOELV. While information regarding the NOAEC for effects on human bone marrow post-date the BOELV, a DNEL based on these bone marrow (threshold) findings would be higher (and hence offer less protection) than the BOELV. The BOELV will therefore be used as the basis of the DN(M)EL for long-term systemic effects associated with benzene, including haematotoxicity and carcinogenicity.

Relevant dose descriptor

Binding exposure limit value for benzene (BOELVbenzene 3.25 mg/m3) is used without modifications.

DNEL chronic systemic by inhalation route = 3.25 mg/m³

Long-term - systemic - dermal

Hazard assessment of the target substance is based on the most hazardous and critical constituent, benzene.

Relevant dose descriptor

The dermal NOAEL is extrapolated from the BOELVbenzene(3.25 mg/m3).

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 4.

Route of exposure (inhalation vs dermal); benzene bioavailability via inhalation is assumed to be 50 % while dermal absorption is only 0.1 % (Modjtahedi and Maibach, 2008).

 

Corrected dermal NOAEL = BOELVbenzene* wRV8h* ABSinh-human/ ABSoral-human

ABS - absorption 

wRV8h-worker respiratory volume (wRV) is 50% greater than the resting standard respiratory volume of
0.2 L/min/kg bw;
 wRV8-hour= (0.2 L/min/kg bw x 1.5 x 60 min x 8 h) / 1000 = 0.144 m3/kg bw

 Corrected dermal NOAEL= 3.25* 0.144 * (50/0.1) = 234 mg/kg bw/day

 

Assessment factors

As the Binding exposure limit value (BOELV) is based on worker life-time exposure no assessment factor is needed.

 

DNEL worker chronic systemic by dermal route = 234 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
3.25 µg/m³
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:
DMEL (Derived Minimum Effect Level)
Value:
234 µg/kg bw/day
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.234 µg/kg bw/day
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

Long-term - systemic - inhalation

Hazard assessment of the target substance is based on the most hazardous component i.e. benzene. The value, DMEL 3.25 µg/m3, is based on the approach used by WHO (2000) which combined estimates of excess risk for leukaemia calculated by Crump (1994) for four models into a geometric mean estimate. The same four models were used for the derivation of this DMEL but estimates of excess risk for acute myelogenous or acute monocytic leukaemia (AMML) calculated by Crump (1994) were used instead of those for leukaemia. For three of the four models, excess risk estimates calculated by Crump (1994) were used. A more recent estimate of excess risk was available for one model (TCEQ, 2007) and this was used instead of the estimate calculated by Crump (1994). The value of 3.25 µg/m3 (1 ppb) is protective against haematotoxicity, genotoxicity and carcinogenicity and results in a geometric mean excess lifetime risk of AMLL of 0.9 x 10-5.  

Relevant dose descriptor

DMEL benzene (3.25 µg/m3) is used without modifications.

DMEL chronic systemic by inhalation route =3.25 µg/m3

Long-term - systemic - dermal

Hazard assessment of the target substance is based on the most hazardous component, benzene.

Relevant dose descriptor

The dermal NOAEL is extrapolated from the inhalation DMELbenzene(3.25 µg/m3).

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 4.

Route of exposure (inhalation vs oral); bioavailability via inhalation is assumed to be 50 % while dermal absorption is only 0.1 % (Modjtahedi and Maibach, 2008).

 

Corrected dermal NOAEL = DMELbenzene* wRV8-h* ABSinh-rat/ ABSoral-human

ABS - absorption 

wRV8-h-worker respiratory volume (wRV) is 50% greater than the resting standard respiratory volume of
0.2 L/min/kg bw;
 wRV8-hour= (0.2 L/min/kg bw x 1.5 x 60 min x 8 h) / 1000 = 0.144 m3/kg bw

 Corrected dermal NOAEL= 3.25 * 0.144 * (50/0.1) = 234 µg/kg bw/day

 

Assessment factors

 As the DMEL is based on general population life-time exposure no assessment factor is needed.

 

DMEL chronic systemic by dermal route = 234 µg/kg bw/day

Long-term - systemic - oral

Hazard assessment of the target substance is based on the most hazardous component, benzene.

Relevant dose descriptor

The oral NOAEL is extrapolated from the inhalation DMELbenzene(3.25 µg/m3).

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 4.

Route of exposure (inhalation vs oral); bioavailability via inhalation is assumed to be 50 % while oral absorption is assumed to be 100 %.

 

Corrected oral NOAEL = DMELbenzene* wRV8-h* ABSinh-human/ ABSoral-human

ABS - absorption 

wRV8-h-worker respiratory volume (wRV) is 50% greater than the resting standard respiratory volume of
0.2 L/min/kg bw;
 wRV8-hour= (0.2 L/min/kg bw x 1.5 x 60 min x 8 h) / 1000 = 0.144 m3/kg bw

 

Corrected oral NOAEL= 3.25 * 0.144 * (50/100) = 0.234 µg/kg bw/day

 

Assessment factors

As the inhalation DMEL is based on general population life-time exposure no assessment factor is needed.

 

DMEL worker chronic systemic by oral route = 0.234 µg/kg bw/day