Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
563 µg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
200 µg/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
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Additional information - workers

For the delineation of DNELs the following exposure patterns are considered:

Since no consumer uses exist for 2-Propanol, 1,1'-[[3-[(3-aminopropyl)amino]propyl]imino]bis-, N-tallow alkyl derivs., the only exposed population considered are workers which are expected to have infrequent and short-term exposures. However, for DNEL calculation chronic exposure conditions were assumed as a worst-case scenario.

Based hereupon, the following critical DNELs with regard to 2-Propanol, 1,1'-[[3-[(3-aminopropyl)amino]propyl]imino]bis-, N-tallow alkyl derivs.

have been identified:

·   DNEL long-term,dermal, systemic

·   DNEL long-term, inhalation, systemic

Long-term exposure - systemic toxicity

1- Dermal DNEL

Identified key study for DNEL derivation is a combined repeated dose study with the reproduction/developmental toxicity screening test by oral route in rats (Takawale, 2010a) which results in a NOAEL of 24 mg/kg body weight per day for systemic effects in parents. Route to route extrapolation must therefore be applied.

Step 1) Relevant dose-descriptor:          

* NOAELoral,systemicrat = 24 mg/kg bw/d

Step 2)Modification of starting point:

* Correction for differences in absorption between oral and dermal routes

No available data is reported for oral and dermal absorptions. The oral and dermal absorption are therefore estimated to 100%. The correction factor is 1.

* Correction for dermal absorption difference between rats and human:

No difference in dermal absorption is expected between rats and humans,no correction factor will be applied.

Correcteddermal,systemic NOAEL = 24 mg/kg bw/d

Step 3) Assessment factors:

*Interspecies: 4(Allometric scaling from rat to human)

*Intraspecies: 5 (differences in sensitivity between workers)

*Exposure duration: 6 (extrapolation from a subacute exposure to a chronic exposure) .

*Dose response: 1(the starting point for DNEL calculation is a NOAEL)

*Quality of database: 1 (there is no reason to assume a special concern)

DNEL Value based on the Correcteddermal, systemicNOAEL = 24 mg/kg bw/d:

= 24 / (4 x 5 x 6 x 1 x 1) = 200 µg/kg bw/ day

2- Inhalation DNEL

Identified key study for DNEL derivation is a combined repeated dose study with the reproduction/developmental toxicity screening test by oral route in rats (Takawale, 2010a) which results in a NOAEL of 24 mg/kg body weight per day for systemic effects in parents. Route to route extrapolation must therefore be applied.

Step 1) Relevant dose-descriptor:          

*NOAELoral,systemicrat = 24 mg/kg bw/d

Step 2)Modification of starting point:

* Correction for differences in absorption between oral and inhalation routes

Due to the low vapour pressure , the potential for generating vapour and thus the risk of inhaling the substance is minimal. In the unlikely event that aerosols or particulates are inhaled, the pulmonary physiology and clearance dynamics would largely favour the oral absorption rather than the inhalation. Therefore, based on the physico-chemical properties of fatty nitriles and their derivatives, the default factor of 2 in case of oral to inhalation extrapolation seems unjustified and is reduced to 1.

* Correction for respiratory volume between rat and human : 1/ 0.38 m3 /kg bw

* Correction for activity driven differences of respiratory volumes in workers compared to workers in rest: 6.7 m3/10 m3

Correctedinhalation, systemicNOAEL = 24 x 1.76 = 42.24 mg/m3

Step 3) Assessment factors:

*Interspecies:1 No correction is made for differences in body size, because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans. Animals and humans breathe at a rate depending on their caloric requirements and this was already taken into account into step 2.The default factor of 2.5 for "remaining differences" is applied.

*Intraspecies: 5 (differences in sensitivity between workers)

*Exposure duration: 6 (extrapolation from a subacute exposure to a chronic exposure) .

*Dose response: 1 (the starting point for DNEL calculation is a NOAEL)

*Quality of database: 1 (there is no reason to assume a special concern)

DNEL Value based on theCorrectedinhalation, systemicNOAEL = 42.24 mg/m3

= 42.24 /(2.5 x 5x 6x 1x 1) = 563 µg/m3

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

No consumer used identified.