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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Eye irritation


The substance is not classified for eye irritation. Therefore, no DNEL has to be derived.


 


 


Skin sensitisation


The substance is classified for skin sensitisation. The available data do not permit a DNEL derivation. Therefore a qualitative approach will be applied for skin sensitisation.


 


 


Repeated dose toxicity


 


DNELs are based on non-accepted read-across candidate :ortho-Diaminotoluene, propoxylated, (EC no. 918-139-9, CAS No. 1228577-90-9) and will be updated upon completion of repeat dose studies (OECD 408, 414) as ordered in ECHA decision on 20-May-2020


 


a.      Worker-DNEL long-term dermal, systemic


 


The NOAEL of 40 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. The available dermal data (calculation according to model by Magnusson at al. (2004)) suggest a dermal absorption figure of 8%.


 


The corrected human dermal NOAEL = oral NOAEL (rat) x (oral rat absorption/dermal human absorption) = 40 x (1/0.08) = 500 mg/kg bw/day.


 


The DNEL long-term dermal, systemic is calculated by applying assessment factors to the NOAEL. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.


For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 72 was calculated using the ECETOC document (2003):


-       Inter-species differences = 4


-       Intra-species differences = 3


-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6


 


Worker-DNEL long-term, dermal, systemic = 500/72 = 7 mg/kg bw/day


 


 


b.     Worker-DNEL long-term inhalation, systemic


 


The NOAEL of 40 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. The NAEC worker (8h) was calculated as prescribed by the guidance:


Corrected inhalatory NOAEC = rat oral NOAEL x (1/sRVrat) x (ABSoral rat/human inhal) x (sRVhuman/wRV)


 


-       N = 40 x (1/0.38) x 1 x (6.7/10)


-       N= 40 x 2.63 x 0.67 = 71 mg/m³.


 


The DNEL long-term inhalation, systemic is calculated by applying assessment factors to the NAEC. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.


For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 18 was calculated using the ECETOC document (2003):


-       Inter-species differences = 1


-       Intra-species differences = 3


-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6


 


Worker-DNEL long-term inhalation, systemic = 71 mg/m³/18 = 3.9 mg/m³


 


 


Mutagenicity and carcinogenicity


 


The substance is not considered mutagenic. Based on the toxicological profile of the substance, carcinogenicity is not expected.


 


 


Reproduction toxicity DNELs are based on non-accepted read-across candidate :ortho-Diaminotoluene, propoxylated, (EC no. 918-139-9, CAS No. 1228577-90-9) and will be updated upon completion of repeat dose studies (OECD 408, 414) as ordered in ECHA decision on 20-May-2020


 


The NOAEL for reproduction toxicity was concluded to be 160 mg/kg bw/day (highest dose tested in OECD 421 study). As no adverse reproduction toxic effects were observed at the highest dose tested, a DNEL for reproduction toxicity is not quantifiable.


Nevertheless in case the highest dose of 160 mg/kg bw/day will be used for a DNEL derivation this will not result in a more critical DNEL compared to the DNEL for repeated dose toxicity. Firstly, the NOAEL for reproduction is far above the one for repeated dose toxicity. Secondly, when deriving a DNEL for reproduction from an OECD 421 assay an additional assessment factor of 2 to 5 should be applied. However, as the assessment factor of 6 for exposure duration (conversion from a sub-acute study to a chronic study) is not applicable for deriving a DNEL for reproduction, the extra assessment factor of 2 to 5 for lower sensitivity of the OECD 421 study does not result in a higher overall assessment factor for reproduction toxicity compared to repeated dose toxicity.


 


 


Reference


 


ECETOC (2003).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Eye irritation


The substance is not classified for eye irritation. Therefore, no DNEL has to be derived.


 


 


Skin sensitisation


The substance is classified for skin sensitisation. The available data do not permit a DNEL derivation. Therefore a qualitative approach will be applied for skin sensitisation.


 


 


Repeated dose toxicity


 


DNELs are based on non-accepted read-across candidate :ortho-Diaminotoluene, propoxylated, (EC no. 918-139-9, CAS No. 1228577-90-9) and will be updated upon completion of repeat dose studies (OECD 408, 414) as ordered in ECHA decision on 20-May-2020


 


a.      General population-DNEL long-term oral, systemic


The NOAEL of 40 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor.


 


The DNEL (oral) is calculated by applying assessment factors to the NOAEL. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.


For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 120 was calculated using the ECETOC document (2003):


-       Inter-species differences = 4


-       Intra-species differences = 5


-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6


 


General population-DNEL long-term, oral, systemic = 40/120 = 0.33 mg/kg bw/day


 


 


b.     General population-DNEL long-term dermal, systemic


The NOAEL of 40 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. The available dermal data (calculation according to model by Magnusson at al. (2004)) suggest a dermal absorption figure of 8%.


 


The corrected human dermal NAEL = oral NOAEL (rat) x (oral rat absorption/dermal human absorption) = 40 x (1/0.08) = 500 mg/kg bw/day.


 


The DNEL (dermal) is calculated by applying assessment factors to the NAEL. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.


For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 120 was calculated using the ECETOC document (2003):


-       Inter-species differences = 4


-       Intra-species differences = 5


-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6


 


General population-DNEL long-term, dermal, systemic = 500/120 = 4.2 mg/kg bw/day


 


 


c.      General population-DNEL long-term, inhalation


 


The NOAEL of 40 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. The NAEC general population (24 h) was calculated as prescribed by the guidance:


Corrected inhalatory NAEC = rat oral NOAEL x (1/sRVrat) x (ABS oral rat/inhal human)


 


-       N= 40 x (1/1.15) x 1


-       N= 40 x 0.87 = 35 mg/m³


 


The DNEL (inhalation) is calculated by applying assessment factors to the NAEC. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.


For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 30 was calculated using the ECETOC document (2003):


-       Inter-species differences = 1


-       Intra-species differences = 5


-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6


 


General population-DNEL long-term inhalation, systemic = 35 mg/m³/30 = 1.2 mg/m³


 


 


Mutagenicity and carcinogenicity


 


The substance is not considered mutagenic. Based on the toxicological profile of the substance, carcinogenicity is not expected.


 


 


Reproduction toxicity


 


The NOAEL for reproduction toxicity was concluded to be 160 mg/kg bw/day (highest dose tested in OECD 421 study). As no adverse reproduction toxic effects were observed at the highest dose tested, a DNEL for reproduction toxicity is not quantifiable.


Nevertheless in case the highest dose of 160 mg/kg bw/day will be used for a DNEL derivation this will not result in a more critical DNEL compared to the DNEL for repeated dose toxicity. Firstly, the NOAEL for reproduction is far above the one for repeated dose toxicity. Secondly, when deriving a DNEL for reproduction from an OECD 421 assay an additional assessment factor of 2 to 5 should be applied. However, as the assessment factor of 6 for exposure duration (conversion from a sub-acute study to a chronic study) is not applicable for deriving a DNEL for reproduction, the extra assessment factor of 2 to 5 for lower sensitivity of the OECD 421 study does not result in a higher overall assessment factor for reproduction toxicity compared to repeated dose toxicity.


 


 


Reference


 


ECETOC (2003).