Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
41.2 µg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100 000
Dose descriptor starting point:
T25
Value:
16.7 mg/kg bw/day
Modified dose descriptor starting point:
T25
Value:
1 030.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point is that for chlorendic acid, which is an impurity in chlorendic anhydride. However, it is identified as a possible carcinogen and therefore the hazard of the substance is based on exposure to this impurity rather than the chlorendic anhydride.

As the endpoint is stipulated as exposure to the whole substance, the dose descriptor starting point is modified to account for the maximum concentration of the acid in the anhydride (3 %).

The extrapolation from oral exposure to inhalation exposure was performed in accordance with the guidance from ECHA, whereby a correction factor of 1.76 is applied. It is assumed that oral absorption by the rat is 50% to inhalation absorption human, in accordance with ECHA. As a worker is considered exposed 8hr/day, 48weeks/y for 40 years the lifetime exposure in the carcinogenicity must be adjusted accordingly by adding a correction factor of 2.8

AF for other interspecies differences:
1
Justification:
Standard rat to human correction factor for dermal exposure.
AF for remaining uncertainties:
25 000
Justification:
high to low extrapolation applied for a risk of 10E-5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
299 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.23 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
300
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
299 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
30
Dose descriptor starting point:
NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
11.7 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100 000
Dose descriptor starting point:
T25
Value:
16.7 mg/kg bw/day
Modified dose descriptor starting point:
T25
Value:
1 558.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point is that for chlorendic acid, which is an impurity in chlorendic anhydride. However, it is identified as a possible carcinogen and therefore the hazard of the substance is based on exposure to this impurity rather than the chlorendic anhydride.

As the endpoint is stipulated as exposure to the whole substance, the dose descriptor starting point is modified to account for the maximum concentration of the acid in the anhydride (3 %).

The extrapolation from oral exposure to dermal exposure was performed in accordance with the guidance from ECHA, whereby a correction factor of 1 is applied. It is assumed that oral absorption by the rat is equal to dermal absorption human, in accordance with ECHA. As a worker is considered exposed 8hr/day, 48weeks/y for 40 years the lifetime exposure in the carcinogenicity must be adjusted accordingly by adding a correction factor of 2.8

AF for other interspecies differences:
4
Justification:
Standard for rat to human exposure via dermal scaling.
AF for remaining uncertainties:
25 000
Justification:
high to low extrapolation applied for a risk of 10E-5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
43 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.56 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
180
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
50
Dose descriptor starting point:
other: LOAEL

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.29 µg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor starting point:
T25
Value:
16.7 mg/kg bw/day
Modified dose descriptor starting point:
T25
Value:
1 374.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point is that for chlorendic acid, which is an impurity in chlorendic anhydride. However, it is identified as a possible carcinogen and therefore the hazard of the substance is based on exposure to this impurity rather than the chlorendic anhydride.

As the endpoint is stipulated as exposure to the whole substance, the dose descriptor starting point is modified to account for the maximum concentration of the acid in the anhydride (3 %).

The extrapolation from oral exposure to inhalation exposure was performed in accordance with the guidance from ECHA, whereby a correction factor of 1.76 is applied. It is assumed that oral absorption by the rat is 50 % of inhalation absorbtion in a human, in accordance with ECHA. As a worker is considered exposed 8hr/day, 48weeks/y for 40 years the lifetime exposure in the carcinogenicity must be adjusted accordingly by adding a correction factor of 2.8.

AF for interspecies differences (allometric scaling):
1
Justification:
Standard correction for rat to human in inhalation exposure
AF for remaining uncertainties:
25 000
Justification:
High to low extrapolation to represent a risk of 10E-5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
149 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.62 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
600
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.042 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
1 200
Dose descriptor starting point:
NOAEC

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.167 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100 000
Dose descriptor starting point:
T25
Value:
16.7 mg/kg bw/day
Modified dose descriptor starting point:
T25
Value:
16.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As there are no consumer uses of chlorendic anhydride, the only route for exposure of the general population is via the environment. If chlorendic anhydride is realeased to the environment it will rapidly hydrolyse to the acid form, so no correction for composition is applied for exposure via the environment.

In the absence of any skin absorption studies, the conservative approach is taken that 100 % of the substance is available through dermal contact.

AF for differences in duration of exposure:
1
Justification:
2 year study viewed as full lifespan
AF for intraspecies differences:
4
Justification:
Standard for rat to human
AF for remaining uncertainties:
25 000
Justification:
high to low extrapolation applied for a risk of 10E-5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
360
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
100
Dose descriptor starting point:
other: LOAEL

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.167 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100 000
Dose descriptor starting point:
T25
Value:
16.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As there are no consumer uses of chlorendic anhydride, the only route for exposure of the general population is via the environment. If chlorendic anhydride is realeased to the environment it will rapidly hydrolyse to the acid form, so no correction for composition is applied for exposure via the environment.

AF for interspecies differences (allometric scaling):
4
Justification:
Standard rat to human conversion
AF for remaining uncertainties:
25 000
Justification:
high to low extrapolation applied for a risk of 10E-5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

The study reports used for this data were not contemporary and did not disclose a NOAEL. The LD50 and information in the studies were used to 'determine' a worst-case NOAEL.