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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:
0.41 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
5.11 mg/m³
Explanation for the modification of the dose descriptor starting point:
Worker Population - NOAEL of 2.9 mg/kg/d / 0.38 m3/kg = 26.3 * [6.7 m3/ 10 m3] = 5.11 mg/m3.
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for differences in duration of exposure:
1
Justification:
Since the starting point is a two-generations study the assessment factor for duration differences is set in REACH guidance as AF = 1.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
5
Justification:
For intraspecies differences (workers) the default factor is 5.
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.41 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
5.11 mg/m³
Explanation for the modification of the dose descriptor starting point:
Worker Population - NOAEL of 2.9 mg/kg/d / 0.38 m3/kg = 26.3 * [6.7 m3/ 10 m3] = 5.11 mg/m3.
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
5
Justification:
For intraspecies differences (workers) the default factor is 5.
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Value:
2.9 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Based on available data on the substance from an in vitro dermal absorption study using human and rat skin, a 10% dermal absorption value is used for the route-to-route extrapolation. Therefore, starting from an oral NOAEL of 2.9 mg/kg/day, the dermal NOAEL would be 29 mg/kg/day (2.9 mg/kg/day/0.1).
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for differences in duration of exposure:
1
Justification:
Since the starting point is a two-generations study the assessment factor for duration differences is set in REACH guidance as AF = 1.
AF for interspecies differences (allometric scaling):
4
Justification:
The allometric scaling factor for the rat is 4.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
5
Justification:
For intraspecies differences (workers) the default factor is 5.
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Value:
29 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Starting point for systemic dermal effects is dermal acute toxicity test: NOAEL = 2.9 mg/kg/day. Taking into account that dermal absorption is, as worst case, 10% , the corrected starting point is 29 mg/kg/day.
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for interspecies differences (allometric scaling):
4
Justification:
The allometric scaling factor for the rat is 4.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
5
Justification:
For intraspecies differences (workers) the default factor is 5.
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

A.- ACUTE TOXICITY. Systemic effects

Oral exposure

Starting point for acute oral effects is NOAEL=2.9 mg/kg/day from 2-generations study (Gill et al 2000). Assessment factors are to be applied as follows:

1.- the allometric scaling factor for the rat is 4; The default factor has been used since no data are available to confirm the absence of toxicokinetic or toxicodynamic differences between mammalian species.

2.- a default factor of 2.5 accounts for additional interspecies differences no related to metabolism. The default value has been used since potential non-metabolism differences between species have not been characterized

3.- for intraspecies differences (workers) the default factor is 10 for consumers.

 

For consumers: DNEL= 2.9/ 100= 0.029 mg/kg/day

No oral exposure is likely for workers.

 

Dermal exposure

Starting point for systemic dermal effects is dermal acute toxicity test: NOAEL = 2.9 mg/kg/day. Taking into account that dermal absorption is, as worst case, 10% (see endpoint 7.1.2), the corrected starting point is 29 mg/kg/day. Assessment factors are to be applied as follows:

(1)    the allometric scaling factor for the rat is 4;

(2)    a default factor of 2.5 accounts for additional interspecies differences;

(3)    for intraspecies differences (workers) the default factor is 5; for consumers 10

 

For consumers: DNEL= 29/ 100= 0.29 mg/kg/day

For workers: DNEL= 29/50 = 0.58 mg/kg/day

 

 

Inhalatory exposure

Starting point is a 2-generations study and 100% absorption is assumed. 

Assessment factors were the same as per oral exposure with exception of allometric scale that does not apply: 25 for general population and 12.5 for workers.

 

Worker Population - NOAEL of 2.9 mg/kg/d /0.38m3/kg = 26.3 * [6.7 m3/ 10 m3] = 5.11 mg/m3.

General Population - NOAEL of 2.9 mg/kg/d /1.15m3/kg = 2.5 mg/m3,

 

Applying the above explained AF:

DNEL inhalation, systemic, chronic worker population = 5.11 / 12.5 = 0.41 mg/m3.

DNEL inhalation, systemic, chronic general population = 2.5 / 25 = 0.1 mg/m3.

 

B.- IRRITATION AND CORROSIVITY

The substance is classified as corrosive as solid form. Due to this known hazard personal protection measures are to be implemented at working place when using the solid. Therefore just accidental dermal exposure is considered.

Quantitative dose descriptor is not possible to derive from available data.

The solution at 31% concentration in water is not irritating (Price 1985b). Therefore no assessment is required for local dermal effects when referring to this preparation.

 

C.- SENSITIZATION

Due to the corrosivity and high dermal toxicity of the test substance dermal exposure should be avoided. Therefore just accidental exposure is to be considered.

A study with a 31% aqueous solution of the substance was conducted.The mixture does not exhibited experimental evidence of sensitizing potential.

 

D.- MUTAGENICITY/ CARCINOGENICITY

There were no indications of a non-threshold mutagenic or tumorigenic response. Therefore DNELs have not been established either for carcinogenicity nor mutagenicity.

E.- REPEAT DOSE TOXICITY:Systemic effects

Since the starting point is a two-generations study the assessment factor for duration differences is set in REACH guidance as AF = 1.

 

Dose-response related issues

Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.

 

Quality of whole database

The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

Dermal exposure

Since no dose descriptor was available from a repeated application dermal toxicity study and dermal exposure is the most probable route of human exposure, it was necessary to derive a corrected dermal NOAEL from the oral NOAEL. The oral dose descriptor was used as the basis for route-to-route extrapolation.

Dermal risk assessment is based on the oral NOAEL of 2.9 mg/kg/day from the 2-generations study.

 

Based on available data on the substance from an in vitro dermal absorption study using human and rat skin, a 10% dermal absorption value is used for the route-to-route extrapolation.

 

Therefore, starting from an oral NOAEL of 2.9 mg/kg/day, the dermal NOAEL would be 29 mg/kg/day (2.9 mg/kg/day/0.1).

 

The following adjustment factors are applied for the identification of the reference MOS:

(1) for duration adjustment a factor of 1 is used

(2) the allometric scaling factor for the rat is 4;

(3) a default factor of 2.5 accounts for additional interspecies differences;

(4) for intraspecies differences (workers) the default factor is 5, for consumers is 10

 

Applying these factors to the oral NOAEL gives:

 

DNEL dermal, systemic, chronic general population = 29/100 = 0.29 mg/kg bw/day,

DNEL dermal, systemic, chronic worker population = 29/50 = 0.58 mg/kg bw/day.

 

Oral exposure

Starting point is NOAEL of 2.9 mg/kg/day. Assuming 100% absorption and the AF described above, critical exposure levels are as follows:

DNEL oral, systemic, chronic general population =2.9/100= 0.029 mg/kg/day

 

Inhalatory exposure

For the chronic inhalation exposure DNELs, the corrected NOAEL was derived as a starting point based on the oral NOAEL of 2.9 mg/kg bw/day, since no study data were available from long term repeated exposure investigations via the inhalation route.This route is considered of minor concern due to the vapour pressure of the substance.

 

The total assessment factor for the worker population, long term DNEL inhalation, systemic = 2.5*5*1*1*1 = 12.5

 

The total assessment factor for the general population, long term DNEL inhalation, systemic = 2.5*10*1*1*1 = 25

 

Differences in respiration volumes were assessedfor converting the oral dose to an inhalation concentration:

 

Worker Population - NOAEL of 2.9 mg/kg/d /0.38m3/kg = 26.3 * [6.7 m3/ 10 m3] = 5.11 mg/m3.

General Population - NOAEL of 2.9 mg/kg/d /1.15m3/kg = 2.5 mg/m3,

 

Applying the above explained AF:

DNEL inhalation, systemic, chronic worker population = 5.11 / 12.5 = 0.41 mg/m3.

DNEL inhalation, systemic, chronic general population = 2.5 / 25 = 0.1 mg/m3.

 

 

The default absorption percentage 100%, for inhalation has also been used in the calculations.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
2.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
General Population - NOAEL of 2.9 mg/kg/d / 1.15 m3/kg = 2.5 mg/m3
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for differences in duration of exposure:
1
Justification:
Since the starting point is a two-generations study the assessment factor for duration differences is set in REACH guidance as AF = 1.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies differences the default factor for consumers is 10
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
2.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
General Population - NOAEL of 2.9 mg/kg/d / 1.15 m3/kg = 2.5 mg/m3
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies differences the default factor for consumers is 10
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.29 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
29 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal exposure Starting point for systemic dermal effects is dermal acute toxicity test: NOAEL = 2.9 mg/kg/day. Taking into account that dermal absorption is, as worst case, 10%, the corrected starting point is 29 mg/kg/day.
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for differences in duration of exposure:
1
Justification:
Since the starting point is a two-generations study the assessment factor for duration differences is set in REACH guidance as AF = 1.
AF for interspecies differences (allometric scaling):
4
Justification:
The allometric scaling factor for the rat is 4.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies differences the default factor for consumers is 10
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.29 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
29 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Starting point for systemic dermal effects is dermal acute toxicity test: NOAEL = 2.9 mg/kg/day. Taking into account that dermal absorption is, as worst case, 10%, the corrected starting point is 29 mg/kg/day.
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for interspecies differences (allometric scaling):
4
Justification:
The allometric scaling factor for the rat is 4.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies differences the default factor for consumers is 10
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.029 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
2.9 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Starting point is NOAEL of 2.9 mg/kg/day.
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for differences in duration of exposure:
1
Justification:
Since the starting point is a two-generations study the assessment factor for duration differences is set in REACH guidance as AF = 1.
AF for interspecies differences (allometric scaling):
4
Justification:
The allometric scaling factor for the rat is 4.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies differences the default factor for consumers is 10
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.029 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
2.9 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Starting point is NOAEL of 2.9 mg/kg/day.
AF for dose response relationship:
1
Justification:
Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.
AF for interspecies differences (allometric scaling):
4
Justification:
The allometric scaling factor for the rat is 4.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 accounts for additional interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies differences the default factor for consumers is 10
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population