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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:
0.53 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):
25
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
13.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

Conversion of the oral NOAEL rat into a corrected inhalatory NOAEC to assess human inhalation exposure is necessary to derive the correct starting point for the inhalation route for which no repeated dose toxicity study was carried out. In the case of oral-to-inhalation extrapolation, 50% (instead of 100%) absorption is assumed for oral absorption, and 100 % for inhalation.

The modification of the descriptor starting point is conducted according to Fig. R.8-3 of ECHA Guidance Chapter R.8, chapter R.8 .4.2 of TGD (ECHA, 2012).

corrected inhalatory N(L)OAEC = oral N(L)OAEL * 1 / sRVrat * ABS oral rat/ ABS inhal-human * sRVhuman/ wRV

= oralN(L)OAEL * 1/ 0.38m3/kg/d * ABS oral_rat / ABS inhal_human * 6.7 m3 (8h) / 10m3 (8h)

= oralN(L)OAEL *2.6316 kg/m3 * 0.5 * 0.67

= 0.882 kg/m3* 15 mg/kg bw/d

= 13.2 mg/m3

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL. Thus, standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov 2012).
AF for differences in duration of exposure:
2
Justification:
A assessment factor 2 is suggested by the ECHA TGD for exposure duration from subchronic (90 day) to chronic (see section R.8.4.3.1, Table R. 8-5) (ECHA, Nov 2012).
AF for interspecies differences (allometric scaling):
1
Justification:
An allometric scaling factor of 4 is suggested by the ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov 2012) for interspecies differences, however, as we have corrected the oral starting point to an inhalation NOAEC, the interspecies differences are already included and no further factor for allometric scaling applies (see TGD, ECHA Example B3 and Table R 8-4).
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
For intraspecies variability, the default assessment factor for worker for systemic effects is 5 (ECHA, Nov 2012).
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R.4.3.1 of TGD (ECHA, Nov 2012).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered to be necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 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:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Converting the oral NOAEL rat into a dermal NOAEL is necessary to derive the correct starting point for the dermal route for which no study was carried out.

As a worst case consideration dermal absorption is considered to be 100%.

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL. Thus, standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov 2012).
AF for differences in duration of exposure:
2
Justification:
A assessment factor 2 is suggested by the ECHA TGD for exposure duration from subchronic (90 day) to chronic (see section R.8.4.3.1, Table R. 8-5) (ECHA, Nov 2012).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 is suggested by the ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov 2012) for interspecies differences.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
For intraspecies variability, the default assessment factor for worker for systemic effects is 5 (ECHA, Nov 2012).
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R.4.3.1 of TGD (ECHA, Nov 2012).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered to be necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The primary endpoint of concern is corrosion/irritation of skin/eye and respiratory tract. No dose-response threshold has been identified for the corrosion/irritation to skin. Inhalation exposure to vapours or mists is reasonably expected to cause moderate-severe irritation. Therefore, a qualitative assessment has been performed in the CSR for the endpoint in workers and consumers.   

Results from the repeated dose toxicity studies in rats indicate systemic effects consistent with stress from long-term ingestion of a corrosive substance (SafePharm, 2006; LPT, 2017).

A NOAEL (15 mg/kg/day) for systemic effects was reported in the DRF (OECD 422) study based on the lowest dose administered (SafePharm, 2006).

In the long-term OECD 408 study, adverse test-item related effects were noted at 50 mg test item/kg b.w. in form of decreased drinking water consumption and effects found during histopathological examinations. At 150 mg test item/kg b.w. effects such as reduced body weight, a decreased food and drinking water consumption, changes in biochemical parameters and organ weights and at histopathological examination were found.

The experimental NOAEL (and in consequence the DNEL for the inhalation as well as the dermal route of exposure) was determined after detailed histopathological examination of the groups treated with 15 and 50 mg test item/kg. By morphology and distribution, the histopathological findings in these dose groups are indicative for phospholipidosis.

The diagnosis of Phospholipidosis was confirmed by Transmission electron microscopy, which is considered to be the most sensitive method for confirming the presence of PL…’ (Chatman et al., 2009). The NOAEL was determined to be 15 mg/kg bw/d.

Due to the corrosive nature of the substance, exposure even to small diluted amounts would be expected to produce immediate skin/eye/respiratory irritation, leading to awareness and voluntary removal from exposure.  Exposure by inhalation of vapours is unlikely as the substance exhibits a very low vapour pressure (0.075 Pa at 25 °C). The focus of occupational health initiatives will be on preventing direct contact with the liquid (spray mists for example), and thus provide sufficient protection against chronic exposure and thus possible systemic effects. Further exposure mitigation is provided by the multipack packaging systems used. As the substance begins to cure immediately upon mixing, exposure risks decrease over time. After curing, the substance is chemically bound in a matrix and poses no downstream exposure risk.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.13 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):
50
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
6.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Conversion of the oral NOAEL rat into a corrected inhalatory NOAEC to assess human inhalation exposure is necessary to derive the correct starting point for the inhalation route for which no repeated dose toxicity study was carried out. In the case of oral-to-inhalation extrapolation, 50% (instead of 100%) absorption is assumed for oral absorption, and 100 % for inhalation. No correction is necessary for the exposure time per week as the oral study is a feeding study (continuous daily exposure).

The modification of the descriptor starting point is conducted according to Fig. R.8-3 of ECHA Guidance Chapter R.8, chapter R.8 .4.2 of TGD (ECHA, 2012) for the general population.

corrected inhalatory N(L)OAEC = oral N(L)OAEL * 1 / sRVrat* ABSoral rat/ ABSinhal-rat*ABSinhal rat/ ABSinhal-human

= oralN(L)OAEL * 1/ 1.15m3/kg/d * ABSoral_rat/ ABSinhal_human

= oralN(L)OAEL *0.87 kg/m3* 0.5

= 0.435 kg/m3* 15 mg/kg bw/d

= 6.5 mg/m3

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL. Thus, standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov 2012).
AF for differences in duration of exposure:
2
Justification:
A assessment factor 2 is suggested by the ECHA TGD for exposure duration from subchronic (90 day) to chronic (see section R.8.4.3.1, Table R. 8-5) (ECHA, Nov 2012).
AF for interspecies differences (allometric scaling):
1
Justification:
An allometric scaling factor of 4 is suggested by the ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov 2012) for interspecies differences, however, as we have corrected the oral starting point to an inhalation NOAEC, the interspecies differences are already included and no further factor for allometric scaling applies (see TGD, ECHA Example B3 and Table R 8-4).
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies variability, the default assessment factor for the general population for systemic effects is 10 (ECHA, Nov 2012).
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R.4.3.1 of TGD (ECHA, Nov 2012).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered to be necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.13 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.075 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):
200
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Converting the oral NOAEL rat into a dermal NOAEL is necessary to derive the correct starting point for the dermal route for which no study was carried out.

As a worst case consideration dermal absorption is considered to be 100%.

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL. Thus, standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov 2012).
AF for differences in duration of exposure:
2
Justification:
A assessment factor 2 is suggested by the ECHA TGD for exposure duration from subchronic (90 day) to chronic (see section R.8.4.3.1, Table R. 8-5) (ECHA, Nov 2012).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 is suggested by the ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov 2012) for interspecies differences.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies variability, the default assessment factor for consumer/ general population for systemic effects is 10 (ECHA, Nov 2012).
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R.4.3.1 of TGD (ECHA, Nov 2012).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered to be necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.075 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.075 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):
200
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Assumptions: Absorption rat = Absorption human ; Frequency of exposure of rat (7d/wk) = Frequency of exposure of general population (7d/wk);

No correction of NOAEL neccessary as the expsoure of rats in the repeated dose toxicity study in rats was continuously (feeding study).

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL. Thus, standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov 2012).
AF for differences in duration of exposure:
2
Justification:
A assessment factor 2 is suggested by the ECHA TGD for exposure duration from subchronic (90 day) to chronic (see section R.8.4.3.1, Table R. 8-5) (ECHA, Nov 2012).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 is suggested by the ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov 2012) for interspecies differences.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies variability, the default assessment factor for the general population for systemic effects is 10 (ECHA, Nov 2012).
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R.4.3.1 of TGD (ECHA, Nov 2012).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered to be necessary.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population