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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:
0.35 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
Modified dose descriptor starting point:
NOAEC
Value:
26.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
According to QSAR predictions obtained from the Danish (Q)SAR database (2004), gastrointestinal absorption is presumed to be 100 %. The observation of toxicity following acute and subacute exposure via gavage administration of triallyl isocyanurate confirms a high substance absorption after oral intake. The inhalative absorption is considered to be in the same order of magnitude as the oral absorption. Therefore no additional factor is applied for differences between the oral and inhalative intake.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable.
AF for differences in duration of exposure:
6
Justification:
Default conversion AF subacute to chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
AF for intraspecies differences:
5
Justification:
Default AF for the worker.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further AFs are required.
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:
0.1 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The absorption difference for the dermal route compared to the oral route is adjusted by the factor 2 due to a moderate skin absorption potential (0.007 mg/cm²/h) assigned to a dermal absorption of 50% based on the QSAR results for triallyl isocyanurate taking into account molecular weight, log Pow and water solubility.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable.
AF for differences in duration of exposure:
6
Justification:
Default conversion AF subacute to chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for differences between rats and humans.
AF for other interspecies differences:
2.5
Justification:
There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
AF for intraspecies differences:
5
Justification:
Default AF for the worker.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further AFs are required.
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

Workers might be exposed to triallyl isocyanurate (liquid) during manufacture, processing, loading or filling in appropriate containers. During formulation, triallyl isocyanurate-coated silica particles (dust) containing 70 % triallyl isocyanurate are obtained.

In general, the calculation of a DNEL is based on the observed effect level which has to be modified as described in “Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, December 2010). Dermal and inhalative intakes are the possible exposure routes for workers.

The establishment of an acute toxicity DNEL set for effects occurring after a single exposure of a few minutes up to 24 hours is unnecessary for triallyl isocyanurate, as the long-term DNEL is sufficient to ensure, that these effects do not occur. Triallyl isocyanurate has a very low vapour pressure (2002-0726-DKP) at room temperature and e.g. at a process temperature of 38 °C (0.00017 Pa at 20 °C and 0.0076 Pa at 38 °C) and as a consequence, the formation of aerosols can be considered negligible. Thus, peak exposure significantly higher than the average daily exposure and the long-term DNEL are very unlikely. In addition since triallyl isocyanurate did not show any irritating effects, no DNELs for local effects were derived.The assessment of hazards for acute systemic effects and local effects are sufficiently covered by derivation of the DNEL for long-term systemic exposure.

As starting point for derivation of the DNEL, a NOAEL of 15 mg/kg bw/day (for systemic effects) was used which was found in a subacute toxicity study performed according to OECD 407 (2003-0756-FGT). In this GLP guideline study triallyl isocyanurate was administered via gavage at concentrations of 5, 15 and 50 mg/kg bw/day for 28 days. Additional satellite animals for the control, mid and high dose group for observation of reversibility, persistence or delayed occurrence of toxic effects were included for 14 days post treatment. A NOAEL of 15 mg/kg/day for male rats was derived based on the significant histopathological changes in the liver still present after the recovery period in the 50 mg/kg bw/day group. A NOAEL of ≥50 mg/kg bw/day is applied for females due to no adverse effects observed after the recovery period. The liver was identified as target organ. Based on sensitivity, the NOAEL value for male rats was selected as relevant dose descriptor.

 

Inhalation

For calculation of the DNEL for long-term inhalative systemic effects, the dose descriptor has to be converted into a corrected starting point by route-to-route extrapolation.

According to QSAR predictions obtained from the Danish (Q)SAR database (2004), gastrointestinal absorption is presumed to be 100 %. The observation of toxicity following acute and subacute exposure via gavage administration of triallyl isocyanurate confirms a high substance absorption after oral intake. The inhalative absorption is considered to be in the same order of magnitude as the oral absorption. Therefore no additional factor is applied for differences between the oral and inhalative intake.

Besides this, the interspecies difference between rat and human has to be taken into account. Therefore, the no observed effect level has to be corrected by the risk assessor 6.7 / (0.38*10) regarding breathing volume and frequency. Thus, the corrected starting point for workers was 26.4 mg/m³/day for inhalation.

 

Subsequently assessment factors (AF) are listed, which have to be taken into account for the final DNEL calculation: remaining interspecies-differences (2.5), intraspecies differences (5), duration extrapolation: subacute - chronic (6).

The DNEL is calculated according to the formula DNEL = (corrected starting point)/(overall AF). Thus, the resulting DNEL for long-term inhalative systemic effects is 0.35 mg/m³ for workers.

 

Dermal

For calculation of the DNEL for long-term dermal systemic effects, the dose descriptor has to be converted into a corrected starting point by route-to-route extrapolation. The absorption difference for the dermal route compared to the oral route is adjusted by the factor 2 due to a moderate skin absorption potential (0.007 mg/cm²/h) assigned to a dermal absorption of 50% based on the QSAR results for triallyl isocyanurate taking into account molecular weight, log Pow and water solubility (for details refer to IUCLID chapter 7.1 toxicokinetics, metabolism and distribution). Thus the corrected starting point for workers was 30 mg/kg bw/day for the dermal route.

Subsequently, following assessment factors are taken into account for the final DNEL calculation: interspecies differences (4), remaining interspecies-differences (2.5), intraspecies differences (5) and duration extrapolation: subacute - chronic (6).

As a consequence, the resulting DNEL for long-term dermal systemic effects is 0.1 mg/kg bw/day for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.18 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
26.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
According to QSAR predictions obtained from the Danish (Q)SAR database (2004), gastrointestinal absorption is presumed to be 100 %. The observation of toxicity following acute and subacute exposure via gavage administration of triallyl isocyanurate confirms a high substance absorption after oral intake. The inhalative absorption is considered to be in the same order of magnitude as the oral absorption. Therefore no additional factor is applied for differences between the oral and inhalative intake.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable.
AF for differences in duration of exposure:
6
Justification:
Default conversion AF subacute to chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
AF for intraspecies differences:
10
Justification:
Default AF for the general population.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further AFs are required.
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:
DNEL (Derived No Effect Level)
Value:
0.05 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The route of exposure is identical.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable.
AF for differences in duration of exposure:
6
Justification:
Default conversion AF subacute to chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for differences between rats and humans.
AF for other interspecies differences:
2.5
Justification:
There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
AF for intraspecies differences:
10
Justification:
Default AF for the general population.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further AFs are required.
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

Direct exposure of the general public via inhalative and dermal route is precluded. However, as the substance is classified with R48 the assessment of man via environment is required according to ECHA guidance. Thus, a DNELs for the general population addressing exposure via oral route is derived.