Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
28 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
Modified dose descriptor starting point:
NOAEC
Value:
705 mg/m³
Explanation for the modification of the dose descriptor starting point:
A fully reliable toxicity study is available for oral route of administration (Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Test (OECD 422)). Appropriate species and dosage were used in this study. 400 mg ASC plus/kg bw. per day can be defined as "No Observed Adverse Effect Level" (NOAEL) for the systemic (and reproduction-developmental) toxicity. Even if an inhalative exposure may occur the most suitable way to determine the systemic toxicity of a solid test substance is normally the oral administration. Additionally the experiences with inhalative administration of dusts of solid substances, i.e. drugs, to humans revealed that such an inhalative exposure leads to a mainly oral ingestion of the substances. This is especially true for ASC plus as (1) the substance is marketed as part of a mixture with water, (2) its very very low vapour pressure and (3) as the measurement of the particle size distribution revealed, that the mean particle size (of the marketed form) is relatively high with only 6 % of the particles < 2 µm representing the small respirable fraction fraction. In consequence an inhalative exposure will result in an oral uptake of nearly 100 % of the administered dosage. The Dose descriptor starting point was derived as follows: NOAEL of 400 mg/kg bw. x 1/0.38 m3/kg/bw x 6.7 m3 / 10 m3 /person = 705 mg/m3 (according to REACH ECHA GD, Example R. 8-2 Workers (Chapter R.8: Characterisation of dose [concentration]-response for human health).
AF for dose response relationship:
1
Justification:
No effects were observed after oral administration to rats of dosages up to and including 400 mg/kg bw..
AF for differences in duration of exposure:
2
Justification:
DENEL based on a fully reliable toxicological study with oral administration of the test article to rats in a Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Study (OECD 422).
AF for interspecies differences (allometric scaling):
1
Justification:
According to ECHA guidance no assessment factor used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
5
Justification:
Standard factor according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable study is used for the derivation of the hazard via oral route
AF for remaining uncertainties:
1
Justification:
A fully reliable study is used for the derivation of the hazard via oral route
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
282 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
3 526 mg/m³
Explanation for the modification of the dose descriptor starting point:
The Dose descriptor starting point was derived as follows: LD50 > 2000 mg/kg bw. x 1/0.38 m3/kg/bw x 6.7 m3 / 10 m3 /person =3526 mg/m3 (according to REACH ECHA GD, Example R. 8-2 Workers (Chapter R.8: Characterisation of dose [concentration]-response for human health).
AF for dose response relationship:
1
Justification:
No higher factor applicable because no effects were observed up to the highest dose.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
5
Justification:
Standard factor for worker according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable study available.
AF for remaining uncertainties:
1
Justification:
AF based on a fully reliable acute oral toxicity study with rats.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 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
Modified dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A reliable oral Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Test (OECD 422) with rats is available. Appropriate species and dosage were used in this study. No effects were observed after oral administration to rats of dosages up to and including 400 mg/kg bw.. Additionally an acute dermal toxicity study revealed no effects up to and including dosages of 2000 mg/kg bw. It is assumed that the resorption after dermal application is similar to the resorption after oral administration.
AF for dose response relationship:
1
Justification:
No effects were observed after oral administration to rats of dosages up to and including 400 mg/kg bw..
AF for differences in duration of exposure:
2
Justification:
DENEL based on a fully reliable toxicological study with oral administration of the test article to rats in a Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Study (OECD 422).
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA guidance a factor of 4 is used for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
5
Justification:
Standard factor for worker according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable study available.
AF for remaining uncertainties:
1
Justification:
A fully reliable study available.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route-to-route extrapolation necessary
AF for dose response relationship:
1
Justification:
No higher factor applicable because no effects were observed up to the highest dose.
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA guidance a factor of 4 is used for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
5
Justification:
Standard factor for worker according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable acute dermal toxicity study available.
AF for remaining uncertainties:
1
Justification:
A fully reliable acute dermal toxicity study available.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
other: NOAEL
AF for dose response relationship:
1
Justification:
No higher factor applicable because no effects were observed up to the highest dose.
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling of 1, " ... since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1)" (ECHA REACH Guidance Chapter R8)
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
5
Justification:
Standard factor for worker according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
AF based on a fully reliable acute dermal toxicity study with rats.
AF for remaining uncertainties:
1
Justification:
AF based on a fully reliable acute dermal toxicity study with rats.

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14 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
Modified dose descriptor starting point:
NOAEC
Value:
705 mg/m³
Explanation for the modification of the dose descriptor starting point:
A fully reliable toxicity study is available for oral route of administration (Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Test (OECD 422)). Appropriate species and dosage were used in this study. 400 mg ASC plus/kg bw. per day can be defined as "No Observed Adverse Effect Level" (NOAEL) for the systemic (and reproduction-developmental) toxicity. Even if an inhalative exposure may occur the most suitable way to determine the systemic toxicity of a solid test substance is normally the oral administration. Additionally the experiences with inhalative administration of dusts of solid substances, i.e. drugs, to humans revealed that such an inhalative exposure leads to a mainly oral ingestion of the substances. This is especially true for ASC plus as (1) the substance is marketed as part of a mixture with water, (2) its very very low vapour pressure and (3) as the measurement of the particle size distribution revealed, that the mean particle size (of the marketed form) is relatively high with only 6 % of the particles < 2 µm representing the small respirable fraction fraction. In consequence an inhalative exposure will result in an oral uptake of nearly 100 % of the administered dosage. The Dose descriptor starting point was derived as follows: NOAEL of 400 mg/kg bw. x 1/0.38 m3/kg/bw x 6.7 m3 / 10 m3 /person = 705 mg/m3 (according to REACH ECHA GD, Example R. 8-2 Workers (Chapter R.8: Characterisation of dose [concentration]-response for human health).
AF for dose response relationship:
1
Justification:
No effects were observed after oral administration to rats of dosages up to and including 400 mg/kg bw..
AF for differences in duration of exposure:
2
Justification:
DNEL based on a fully reliable toxicological study with oral administration of the test article to rats in a Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Study (OECD 422).
AF for interspecies differences (allometric scaling):
1
Justification:
According to ECHA guidance no assessment factor used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
10
Justification:
Standard factor according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable study is used for the derivation of the hazard via oral route.
AF for remaining uncertainties:
1
Justification:
A fully reliable study is used for the derivation of the hazard via oral route.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
141 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
3 526 mg/m³
Explanation for the modification of the dose descriptor starting point:
The Dose descriptor starting point was derived as follows: LD50 > 2000 mg/kg bw. x 1/0.38 m3/kg/bw x 6.7 m3 / 10 m3 /person =3526 mg/m3 (according to REACH ECHA GD, Example R. 8-2 Workers (Chapter R.8: Characterisation of dose [concentration]-response for human health).
AF for dose response relationship:
1
Justification:
No higher factor applicable because no effects were observed up to the highest dose.
AF for interspecies differences (allometric scaling):
1
Justification:
According to ECHA guidance no assessment factor used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
10
Justification:
Standard factor for general public according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable acute oral toxicity study is used for the derivation of the hazard via oral route
AF for remaining uncertainties:
1
Justification:
A fully reliable acute oral toxicity study is used for the derivation of the hazard via oral route

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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
Modified dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A reliable oral Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Test (OECD 422) with rats is available. Appropriate species and dosage were used in this study. No effects were observed after oral administration to rats of dosages up to and including 400 mg/kg bw.. Additionally an acute dermal toxicity study revealed no effects up to and including dosages of 2000 mg/kg bw. It is assumed that the resorption after dermal application is similar to the resorption after oral administration.
AF for dose response relationship:
1
Justification:
No effects were observed after oral administration to rats of dosages up to and including 400 mg/kg bw..
AF for differences in duration of exposure:
2
Justification:
DNEL based on a fully reliable toxicological study with oral administration of the test article to rats in a Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Study (OECD 422).
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA guidance a factor of 4 is used for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
10
Justification:
Standard factor for general population according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable OECD Guideline 422 study with oral administration is available.
AF for remaining uncertainties:
1
Justification:
A fully reliable OECD Guideline 422 study with oral administration is available.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route-to-route extrapolation necessary
AF for dose response relationship:
1
Justification:
No higher factor applicable because no effects were observed up to the highest dose
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA guidance a factor of 4 is used for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
10
Justification:
Standard factor according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable acute dermal toxicity study is used.
AF for remaining uncertainties:
1
Justification:
A fully reliable acute dermal toxicity study is available.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.45 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
other: NOAEL
AF for dose response relationship:
1
Justification:
No higher factor necessary because no effects were observed up to the highest dose
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling of 1, " ... since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1)" (ECHA REACH Guidance Chapter R8)
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
10
Justification:
Standard factor according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
AF based on a fully reliable acute dermal toxicity study with rats.
AF for remaining uncertainties:
1
Justification:
AF based on a fully reliable acute dermal toxicity study with rats.

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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
Modified dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A toxicological study with oral administration is used for extrapolation to the hazard via oral route of the general population. A fully reliable toxicity study is available for oral route of administration (Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Test (OECD 422)). Appropriate species and dosage were used in this study. 400 mg ASC plus/kg bw. per day can be defined as "No Observed Adverse Effect Level" (NOAEL) for the systemic (and reproduction-developmental) toxicity.
AF for dose response relationship:
1
Justification:
No effects were observed after oral administration to rats of dosages up to and including 400 mg/kg bw..
AF for differences in duration of exposure:
2
Justification:
DNEL based on a fully reliable toxicological study with oral administration of the test article to rats in a Combined Repeated Dose with the Reproduction/Developmental Toxicity Screening Study (OECD 422).
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA guidance a factor of 4 is used for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
10
Justification:
Standard factor according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable study is used for the derivation of the hazard via oral route.
AF for remaining uncertainties:
1
Justification:
No further assessement factor necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to rout extrapolation necessary.
AF for dose response relationship:
1
Justification:
No effects were observed after oral administration to rats of with dose of 2000 mg/kg bw..
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA guidance a factor of 4 is used for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
"Remaining differences"
AF for intraspecies differences:
10
Justification:
Standard factor according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
A fully reliable acute oral toxicity study is used for the derivation of the hazard via oral route
AF for remaining uncertainties:
1
Justification:
A fully reliable acue oral toxicity study is used for the derivation of the hazard via oral route

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population