Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.88 mg/m³
Most sensitive endpoint:
sensitisation (respiratory tract)
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:

Benzene-1,2,4-tricarboxylic acid 1,2-anhydride, oligomeric reaction products with ethane-1,2-diol and glycerol was tested in an oral 90 -day repeated dose toxicity study according to OECD 408 guideline. In this study, at 1000/750 mg/kg bw/day, mortality prevents conclusion of a lack of effect on body function and therefore, excluding local irritancy and in terms of systemic toxicity only, it may be postulated that a NOAEL is 100 mg/kg bw/day.

The ‘No Observed Effect Level’ (NOEL) for repeated toxicity was considered to be 100 mg/kg bw/day. Therefore, NOAEC is ((100/2)/(1/0.38))*0.67 = 88.2 mg/m3

 

Since only a sub-chronic oral toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation routes. According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route specific information on thestarting route, to include a default factor of 2 in the case of oral-inhalation extrapolation. On the assumption, that in general, dermal absorption will not be higher than oral absorption, no default factor is introduced for the oral to dermal extrapolation. The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 1 in case of oral to dermal extrapolation.

This approach will be taken forward to DNEL derivation.

AF for dose response relationship:
2
Justification:
Duration of exposure is based on an OECD 408 90-day study and therefore an assessment factor for duration extrapolation of 2 has been applied (e.g subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Derived endpoint is based on a laboratory Rat study and therefore an allometric scaling factor of 4 has been applied in accordance with Table R. 8-3 Allometric scaling factors for different species as compared to humans
AF for other interspecies differences:
2.5
Justification:
Default assessment factor applied for interspecies differences e.g. remaining differences Table R.8.6 Default Assessment factors
AF for intraspecies differences:
5
Justification:
Default assessment factor applied for intraspecies differences for worker population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (respiratory tract)
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:
1 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):
100
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor is introduced for the oral to dermal extrapolation. The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 1 in case of oral to dermal extrapolation. Based on the log Kow of 0.3 and molecular weight of the substance (920), the skin permeability according to Fitzpatrick et al (2004) of the substance is considered to be non- permeable to the skin based on a calculated Log skin permeation coefficient of -12.214 and therefore confirms that a default factor of 1 for oral to dermal extrapolation is a conservative estimate and appropriate.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
2.5
AF for other interspecies differences:
4
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

The main hazard for workers is the inhalation of the substance. Health effects at the workplace, respiratory sensitisation and respiratory irritation, have been reported for a component present in the substance as described in Section 1.2. The occupational exposure limit is considered to reduce the risk for such effects to an acceptable level. The dermal exposure limit is derived from the oral toxicity study.

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

The general population is not exposed because the substance as described in Section 1.2 is used in industrial environment only. There is no release to the environment, which could also cause exposure of the general population.