Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
other: 529 mg/m³ cNOAEC
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is necessary, as the original route of the study used in the estimation of the DNEL was conducted via oral.

AF for dose response relationship:
1
Justification:
Study design includes dose range considered adequate to address potential dose respose.
AF for differences in duration of exposure:
6
Justification:
Duration of exposure of original study combined with dose level and corrected NOAEC are considered adequate to address work exposure
AF for other interspecies differences:
2.5
Justification:
standard animal study conducted in rats
AF for intraspecies differences:
5
Justification:
standars animal study
AF for the quality of the whole database:
1
Justification:
dataset is adequate for evaluation of the substance
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:
DNEL (Derived No Effect Level)
Value:
2.5 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):
120
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:

Based on the a 28 -day repeated-dose oral toxicity study in Sprague-Dawley rats provided a NOAEL of 300 mg/kg bw/day. Assuming 100% absorption, the NOAEL of 300 mg/kg bw/day was chosen as startpoint for the DNEL derivation.

AF for dose response relationship:
1
Justification:
Study design for a 28-day oral repeated dose provided a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Duration of exposure of original study combined with dose levels considered are adequate to address work exposure
AF for interspecies differences (allometric scaling):
4
Justification:
REACH Guidance for DNEL, when convert oral NOAEL rat (in mg/kg bw/day) into dermal N(L)OAEL rat (in mg/kg
bw/day) asks for interspecies differences to apply factor for allometric scaling (4 for rat).
Justification:
standard animal study conducted in rats
AF for intraspecies differences:
5
Justification:
standard animal study
AF for the quality of the whole database:
1
Justification:
dataset is adequate for evaluation of the substance
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Short Term DNELs - Since acute DNELs for workers should only be derived in case an acute toxicity hazard (leading to C&L) has been identified and the potential for peak exposure is unlikely, it has been concluded that these DNELs are not required for the complete evaluation of this substance.

High peak exposure are usually assessed for the inhalation route (ECHA Guidance R.8, page 106), a valued of 5000 mg/m³ for acute inhalation toxicity was selected to be used as surrogate of dibutyl maleate. In addition, the lack of toxicity in the oral acute study, the low vapor pressure and the general lack of significant effects seen with DOM in the workplace indicate low level of concern.

 

Long-Term DNELs - All long-term DNELs were calculated using the most reliable data available. The ECETOC (2010) Draft Default Assessment Factors from animal data were selected for the DNEL derivation. Also, the ECETOC Guidance for Assessment Factors to derive DNELs (2003) was applied.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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

In accordance with Annex I (1.4 Step 4) of the REACH regulation there is no need to derive DNEL(s) for the general population when there is neither direct nor indirect exposure (via environment) to consumers from the manufactured substance through its uses at the manufacturing site and any downstream uses for the production of polymers and chemicals.