Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

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

Local effects

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 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):
150
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assume 100% dermal absorption
AF for dose response relationship:
1
Justification:
NOAEL is used
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
pharmacodynamic
AF for intraspecies differences:
2.5
Justification:
pregnant females are more sensitive than worker population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
Read-across is taken from a category member which is more sensitive than others
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information

Local effects

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

A valid combined 28-day oral repeated dose study with reproductive toxicity screening (OECD 421) of tripropenyl succinic anhydride (TSA) in Wistar rats (Takawale, 2013) is available to derive oral/dermal DNELs. Doses were 50, 150 and 250 mg/kg bw/d in a corn oil vehicle. Systemic effects were observed as decreased body weight at mid and high doses in both males and females, decreased food consumption in mid and high dose males, and histopathology of the kidney (vacuolation, degeneration and regeneration of the tubules) and increased kidney weight in mid and high dose females. Local toxicity was seen as minor submucosal mixed cell infiltration, submucosal congestion with hemorrhage, and perivasculitis. Toxic effects of the corn oil vehicle may account for some of these effects. The systemic NOAEL was 50 mg/kg/d.   While oral exposure to a worker is not expected, this calculation also represents the systemic DNEL from dermal exposure.   The derivation is performed according the guidance of ECHA (2010), except for minor modifications of selected assessment factors. The intraspecies assessment factor is revised to 2.5 from 5 to account for already accommodated intraspecies variability by choosing the systemic effects observed in pregnant females, a more sensitive subgroup of the combined male/female population. The read-across assessment factor is 1 rather than 2, as experimental data shows that tripropenyl succinic anhydride may be more toxic than TPSA and other C8-C12 alkenyl succinic anhydrides. It was observed in 14-day dose range finding studies that the NOEL for TSA was lower than the NOEL for TPSA (300 mg/kg bw)(Lee, 2013).

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 may, in some situations, be exposed to chemicals in the water or soil, via environmental contamination. This is not applicable to members of the C8-C12 Alkenyl Succinic Anhydride category, as these substances are hydrolytically unstable.  Quantitative DNELs are not derived