Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.89 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance 2012 and ECETOC 2010
Overall assessment factor (AF):
13
Dose descriptor starting point:
NOAEC
Value:
62.5 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
47.32 mg/m³
Explanation for the modification of the dose descriptor starting point:

Adaption of the respiratory volume from 6 to 8 h exposure (ECHA 2012, table R.8-2)

AF for dose response relationship:
1
Justification:
The NOAEC is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
Standard extrapolation subchronic to chronic exposure (ECHA 2012)
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable when setting an inhalation DNEL based on an inhalation animal study (ECHA 2012)
AF for other interspecies differences:
1
Justification:
not applicable
AF for intraspecies differences:
3
Justification:
ECETOC value (2010) based on the database of Hattis et al (2002): the 95th or the 90th percentile for the intraspecies AF of the general human population can be estimated as approximately 6 and 4, respectively." The AF for workers is accordingly lower. Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1
Justification:
There is evidence that multiplicative association between inter- and intraspecies AF is overly conservative and that the inclusion of a factor for remaining differences is unnecessary (ECETOC 2010)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.89 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC 2010
Overall assessment factor (AF):
13
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC
Value:
62.5 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
47.32 mg/m³

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.54 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance 2012 and ECETOC 2010
Overall assessment factor (AF):
3.9
Dose descriptor:
NOAEC
Value:
10 mg/m³
AF for dose response relationship:
1
Justification:
The NOAEC is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
No extrapolation for exposure duration (EECTOC 2010)
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable when setting an inhalation DNEL based on an inhalation animal study (ECHA 2012)
AF for other interspecies differences:
1
Justification:
not applicable
AF for intraspecies differences:
3
Justification:
ECETOC (2010) value based on the database of Hattis et al (2002): the 95th or the 90th percentile for the intraspecies AF of the general human population can be estimated as approximately 6 and 4, respectively." The AF for workers is accordingly lower. (Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436)
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1.31
Justification:
There is evidence that multiplicative association between inter- and intraspecies AF is overly conservative and that the inclusion of a factor for remaining differences is unnecessary (ECETOC 2010). An factor of 1.31 is applied here for the adaption of the respiratory volume from 6 to 8 h exposure (ECHA 2012, table R.8-2).
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.54 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance 2012 and ECETOC 2010
Overall assessment factor (AF):
3.9
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance 2012 and ECETOC 2010
Overall assessment factor (AF):
62
Dose descriptor starting point:
NOAEC
Value:
62.5 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
36 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

0.29 m3/kg as correction for rat standard breathing volume, 6 hrs (ECHA R.8, 2012)

5 m3/10m3 as correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/5 m3) is required (ECHA R.8, 2012)

AF for dose response relationship:
1
Justification:
The NOAEC is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
Standard extrapolation subchronic to chronic exposure (ECHA 2012)
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4 (ECHA 2012).
AF for other interspecies differences:
1
Justification:
not applicable
AF for intraspecies differences:
3
Justification:
ECETOC (2010) value based on the database of Hattis et al (2002): the 95th or the 90th percentile for the intraspecies AF of the general human population can be estimated as approximately 6 and 4, respectively." The AF for workers is accordingly lower. Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1.5
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance 2012 and ECETOC 2010
Overall assessment factor (AF):
62
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC
Value:
62 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
36 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

see long-term DNEL

Local effects

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

Derivation of DNEL (Inhalation, long-term, systemic)

 

Calculation from the 90d rat inhalation study
Description Value/ factor Remark
Step 1) Relevant dose-descriptor NOAEC systemic: 62.5 mg/m3 Key study is a subchronic study with a systemic NOAEL of 62.5 mg/m3 (6h/d; 5d/w)
Step 2) Modification of starting point 1,31 Adaption of the respiratory volume from 6 to 8 h exposure (ECHA 2012, table R.8-2)
NAEL worker (mg/m3) 47,32  
Step 3) Assessment factors    
Interspecies 1 not applicable when setting an inhalation DNEL based on an inhalation animal study (ECHA 2012).
Intraspecies 3 ECETOC value based on the database of Hattis et al (2002): the 95th or the 90th percentile for the intraspecies AF of thegeneral human populationcan be estimated as approximately 6 and 4, respectively." The AF forworkersis accordingly lower. Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436
Exposure duration 2 Standard extrapolation subchronic to chronic exposure (ECHA 2012)
Dose response 1 The NOAEL is reliable. No adjustment is required.
Quality of database 1 The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
Remaining uncertainties 1 There is evidence that multiplicative association between inter- and intraspecies AF is overly conservative and that the inclusion of a factor for remaining differences is unnecessary (ECETOC 2010)
Overall AF 6  
DNEL    
Based upon a NOAEL of 62.5mg/m3 for rats, for 90 d by the inhalative route. 7,89 Using a total factor (POD modifier and AF) of 13 (1.31 x 1 x 5 x 2 x 1 x 1 x 1) a DNEL long-term systemic , inhal, worker of 7.89 mg/m3 is derived.

 

Derivation of DNEL (Inhalation, long-term, local)

 

Calculation from the 90d rat inhalation study
Description Value/ factor Remark
Step 1) Relevant dose-descriptor NOAEC local: 10 mg/m3 Key study is a subchronic study with a local NOAEC of 10 mg/m3 (6h/d; 5d/w)
Step 2) Modification of starting point 1,31 Adaption of the respiratory volume from 6 to 8 h exposure (ECHA 2012, table R.8-2)
NAEL worker (mg/m3) 7,63  
Step 3) Assessment factors    
Interspecies 1 not applicable when setting an inhalation DNEL based on an inhalation animal study (ECHA 2012).
Intraspecies 3 ECETOC value based on the database of Hattis et al (2002): the 95th or the 90th percentile for the intraspecies AF of thegeneral human populationcan be estimated as approximately 6 and 4, respectively." The AF forworkersis accordingly lower. (Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436)
Exposure duration 1 No extrapolation for exposure duration (EECTOC 2010)
Dose response 1 The NOAEL is reliable. No adjustment is required.
Quality of database 1 The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
Remaining uncertainties 1 There is evidence that multiplicative association between inter- and intraspecies AF is overly conservative and that the inclusion of a factor for remaining differences is unnecessary (ECETOC 2010)
Overall AF 3  
DNEL    
Based upon a NOAEC local of 10 mg/m3 for rats, for 90 d by the inhalative route. 2,54 Using a total factor (POD modifier and AF) of 3.9 (1.31 x 1 x 3 x 1 x 1 x 1 x 1) a DNEL long-term, inhal, worker of 4.7 mg/m3 is derived.

Derivation of DNEL (dermal, long-term, systemic)

 

In absence of a relevant dermal study as potential key study for dermal DNEL calculations, three studies were available to derrive this DNEL from other routes: Two chronic oral studies in rats and mice of good quality (Klimisch 2) and a subchronic guideline study in rats with inhalative exposure of high quality (Klimisch 1). DNELs were derrived from all three studies with the respective AFs (see below). The DNEL calculations provided a consistent picture of a narrow DNEL range between 1.00 and 1.11 mg/kg bw/d. It was understood in a weight-of-evidence approach that the consistency within the DNEL range, based on data from two different routs and two different species, provide additional evidence that the selected lowest DNEL ensures a sufficiently safe level for workers via the dermal route.

Calculation from the  90d inhal rat  DNEL KEY STUDY (highest reliability & most sensitive DNEL)
Description Value/ factor Remark
Step 1) Relevant dose-descriptor NOAEL: 62 mg/m3  DNEL key study is the subchronic study in rat with a NOAEL of 62.5 mg/m3; 6h/d 5d/w
Step 2) Modification of starting point 0.29 m³/kg

5 m3/10 m3
Correction for rat standard breathing volume, 6 hrs (ECHA R.8, 2012)
-Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m3/5 m3) is required (ECHA R.8, 2012)
NAEL worker (mg/kg bw/d) 36,0  
Step 3) Assessment factors    
Interspecies 4 Allometric scaling rat to humans AF 4 (ECHA 2012).
Intraspecies 3 ECETOC value based on the database of Hattis et al (2002): the 95th or the 90th percentile for the intraspecies AF of thegeneral human populationcan be estimated as approximately 6 and 4, respectively." The AF forworkersis accordingly lower. Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436
Exposure duration 2 Standard extrapolation subchronic to chronic exposure (ECHA 2012)
Dose response 1 The NOAEL is reliable. No adjustment is required.
Quality of database 1 The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
Remaining uncertainties 1,5 Remaining differences covering route-to-route extrapolation
Overall AF 36  
DNEL    
Based upon a NOAEL of 20 mg/kg bw/d for rats, for 1 yr by the oral route. 1,00 Using a total factor (POD modifier and AF) of 62 (1.72 x 4 x 3 x 2 x 1 x 1 x 1.5) a DNELlong-term systemic, dermal, workerof 1,0 mg/kg bw/d is derived.

Calculation from the  12m oral rat study DNEL SUPPORTING STUDY
Description Value/ factor Remark
Step 1) Relevant dose-descriptor NOAEL: 400 ppm = 400 mg/L = approx. 20 mg/kg bw/d  Supporting study is the chronic study with a NOAEL of approx. 20 mg/kg/d; water consumption estimate of 50 mL/ kg bw/d according to ECHA, 2012, Table R.8-12 
Step 2) Modification of starting point 1 An additional safety factor for route extrapolation is not appropriate as the existing data are indicating a minor toxic potential of the substance after dermal administration compared to oral administration.
NAEL worker (mg/kg bw/d) 20,0  
Step 3) Assessment factors    
Interspecies 4 Allometric scaling rat to humans AF 4 (ECHA 2012).
Intraspecies 3 ECETOC value based on the database of Hattis et al (2002): the 95th or the 90th percentile for the intraspecies AF of thegeneral human populationcan be estimated as approximately 6 and 4, respectively." The AF forworkersis accordingly lower. Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436
Exposure duration 1 Chronic exposure - AF for extrapolation is not necessary (ECHA 2012). 
Dose response 1 The NOAEL is reliable. No adjustment is required.
Quality of database 1,5 Only short abstract of the chronic study available
Remaining uncertainties 1 There is evidence that multiplicative association between inter- and intraspecies AF is overly conservative and that the inclusion of a factor for remaining differences is unnecessary (ECETOC 2010)
Overall AF 18  
DNEL    
Based upon a NOAEL of 20 mg/kg bw/d for rats, for 1 yr by the oral route. 1,11 n.a.

Calculation from the  12 m oral mouse DNEL SUPPORTING STUDY
Description Value/ factor Remark
Step 1) Relevant dose-descriptor NOAEL: 200 ppm = 200 mg/L = approx. 33-40 mg/kg bw/d  Supporting study is the chronic study in mice with a NOAEL of 33-40 mg/kg/d; water consumption estimate of 167-200 mL/ kg bw/d according to ECHA, 2012, Table R.8-12 
Step 2) Modification of starting point 1 An additional safety factor for route extrapolation is not appropriate as the existing data are indicating a minor toxic potential of the substance after dermal administration compared to oral administration.
NAEL worker (mg/kg bw/d) 33,4  
Step 3) Assessment factors    
Interspecies 7 Allometric scaling mouse to humans AF 7 (ECHA 2008).
Intraspecies 3 ECETOC value based on the database of Hattis et al (2002): the 95th or the 90th percentile for the intraspecies AF of thegeneral human populationcan be estimated as approximately 6 and 4, respectively." The AF forworkersis accordingly lower. Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436
Exposure duration 1 Chronic exposure - AF for extrapolation is not necessary (ECHA 2012). 
Dose response 1 The NOAEL is reliable. No adjustment is required.
Quality of database 1,5 Only short abstract of the chronic study available
Remaining uncertainties 1 There is evidence that multiplicative association between inter- and intraspecies AF is overly conservative and that the inclusion of a factor for remaining differences is unnecessary (ECETOC 2010)
Overall AF 31,5  
DNEL    
Based upon a NOAEL of 20 mg/kg bw/d for rats, for 1 yr by the oral route. 1,06 n.a.

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Justification:
The NOAEC is reliable. No adjustment is required.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.64 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance 2012 and ECETOC 2010
Overall assessment factor (AF):
52
Dose descriptor starting point:
NOAEL
Value:
33.4 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
33.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL of 200 ppm = 33-40 mg/kg/d; water consumption estimate of 167-200 mL/ kg bw/d according to ECHA, 2012, Table R.8-12

AF for dose response relationship:
1
Justification:
The NOAEC is reliable. No adjustment is required.
AF for differences in duration of exposure:
1
Justification:
Chronic exposure - AF for extrapolation is not necessary (ECHA 2012)
AF for interspecies differences (allometric scaling):
7
Justification:
Allometric scaling mouse to humans (ECHA 2012).
AF for other interspecies differences:
1
Justification:
not applicable
AF for intraspecies differences:
5
Justification:
ECETOC value (2010) based on the database of Hattis et al (2002) and other scientific literature: the 95th or the 90th percentile for the intraspecies AF of the general human population can be estimated as approximately 6 and 4, respectively.". Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436)
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
AF for remaining uncertainties:
1.5
Justification:
Only short abstract of the chronic study available
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

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

There was no relevant exposure of the general population identified in the CSA.

Only (long-term) oral exposure is considered necessary to calculate scenarios for exposure via the environment (e.g. drinking water). In this context, the dermal and inhalation pathway was not considered as relevant.

Derivation of DNEL (general population, oral long-term, systemic)

Two studies were available to derrive this DNEL, both chronic oral studies, in rats and mice, and of good quality (Klimisch 2). DNELs were derrived from both studies with the respective AFs (see below). The DNEL calculations provided a consistent picture of a narrow DNEL range between 0.64 and 0.67 mg/kg bw/d. It was understood in a weight-of-evidence approach that the consistency within the DNEL range provides additional evidence that the selected lowest DNEL ensures a sufficiently safe level for the general population via the oral route via the environment.

Calculation from the  12 m oral mouse DNEL key STUDY
Description Value/ factor  Remark
Step 1) Relevant dose-descriptor NOAEL: 200 ppm = 200 mg/L = approx. 33-40 mg/kg bw/d  DNEL key study is the chronic study in mice due to the slightly lower DNEL as that derrived from the chronic rat study; NOAEL of 200ppm = 33-40 mg/kg/d; water consumption estimate of 167-200 mL/ kg bw/d according to ECHA, 2012, Table R.8-12 
Step 2) Modification of starting point 1 No route-to-route extrapolation required
NAEL worker (mg/kg bw/d) 33,4  
Step 3) Assessment factors    
Interspecies 7 Allometric scaling mouse to humans AF 7 (ECHA 2008).
Intraspecies 5  ECETOC value (2010) based on the database of Hattis et al (2002) and other scientific literature: the 95th or the 90th percentile for the intraspecies AF of the general human population can be estimated as approximately 6 and 4, respectively.". Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436)
Exposure duration 1 Chronic exposure - AF for extrapolation is not necessary (ECHA 2012). 
Dose response 1 The NOAEL is reliable. No adjustment is required.
Quality of database 1,5  only short abstract of the chronic study available
Remaining uncertainties 1 There is evidence that multiplicative association between inter- and intraspecies AF is overly conservative and that the inclusion of a factor for remaining differences is unnecessary (ECETOC 2010)
Overall AF 52,5  
DNEL    
Based upon a NOAEL of 33.4 mg/kg bw/d for mice, for 1 yr by the oral route. 0,64 Using a total factor (POD modifier and AF) of 52 (1 x 7 x 5 x 1 x 2 x 1.5 x 1) a DNELlong-term, oral, gen popof 0.64 mg/kg bw/d is derived.

Calculation from the  12m oral rat study DNEL supporting study
Description Value/ factor  Remark
Step 1) Relevant dose-descriptor NOAEL: 400 ppm = 400 mg/L = approx. 20 mg/kg bw/d  DNEL supporting study is the chronic study in rats due to the slightly higher DNEL as that derrived from the chronic mouse study; NOAEL of 400ppm = of approx. 20 mg/kg/d; water consumption estimate of 50 mL/ kg bw/d according to ECHA, 2012, Table R.8-12 
Step 2) Modification of starting point 1 No route-to-route extrapolation required
NAEL worker (mg/kg bw/d) 20,0  
Step 3) Assessment factors    
Interspecies 4 Allometric scaling rat to humans AF 4 (ECHA 2012).
Intraspecies 5  ECETOC value (2010) based on the database of Hattis et al (2002) and other scientific literature: the 95th or the 90th percentile for the intraspecies AF of the general human population can be estimated as approximately 6 and 4, respectively.". Hattis D, Baird S, Goble R. 2002. A straw man proposal for a quantitative definition of the RfD. Drug Chem Toxico 25:403-436)
Exposure duration 1 Chronic exposure - AF for extrapolation is not necessary (ECHA 2012). 
Dose response 1 The NOAEL is reliable. No adjustment is required.
Quality of database 1,5  only short abstract of the chronic study available
Remaining uncertainties 1 There is evidence that multiplicative association between inter- and intraspecies AF is overly conservative and that the inclusion of a factor for remaining differences is unnecessary (ECETOC 2010)
Overall AF 30  
DNEL    
Based upon a NOAEL of 20 mg/kg bw/d for rats, for 1 yr by the oral route. 0,67 n.a.