Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Acute / short-term DNELs - systemic and local effects - have not been derived because Formamidopropyldimethylbetain does not meet the criteria to be classified dangerous for acute toxicity. Furthermore, Formamidopropyldimethylbetain is not classified dangerous for skin/eye irritation/corrosion, skin sensitisation, respiratory irritation/corrosion and respiratory sensitisation.

Long-term DNELs – local effects - have not been derived because Formamidopropyldimethylbetain does not meet the criteria to be classified dangerous for skin/eye irritation/corrosion, skin sensitisation, respiratory irritation/corrosion and respiratory sensitisation.

 

Long-term DNELs – systemic effects:

Formamidopropyldimethylbetain has been tested up to and including the limit dose for repeated dose toxicity testing stipulated in Guideline B.9 and B.26 of Council Regulation (EC) No 440/2008 laying down the test methods pursuant to Regulation (EC) No 1907/2006 (REACH). Since up to and including the limit dose of 1000 mg/kg bw/d, the animals were free of any critical substance related effects, it can be assumed that Formamidopropyl¬dimethylbetain has no intrinsic hazardous toxic activity relevant to humans by single or repeated oral or dermal exposure. Because of this proven absence of intrinsic hazardous activity, Formamidopropyl¬dimethylbetain poses no risk relevant to humans by repeated dermal exposure and a calculation of a corresponding Derived No Effect Level (DNEL) is not appropriate as no NOAEL based on toxic effects could be determined in adequately conducted studies.

In the oral and dermal repeated dose toxicity studies the NOAEL is >= 1000 mg/kg bw/day for male and female rats. A point of departure for the assessment of systemic toxicity after oral and dermal exposure could not be derived due to the lack of substance related critical health effects up to and including the limit dose of the studies design. As an actual value for the NOAEL could not be determined due to limit dose testing in these study types, it could be much higher than 1000 mg/kg bw/day. Formamidopropyldimethylbetain being a substance in solution has the potential to be dermally absorbed. The substance however is expected to be too hydrophilic to cross the lipid rich environment of the stratum corneum (miscible with water; log Po/w: -3.3). As the criteria for 10% dermal absorption as given in the TGD (2) (MW > 500 and log Po/w < -1) are not met, 50% dermal absorption of Formamidopropyldimethylbetain is proposed for risk assessment purposes. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

A 90-day oral repeated-dose study is available.The derivation of a Consumer DNEL long-term oral is not indicated due to the lack of an appropriate point of departure (NOAEL >= 1000 mg/kg bw/d). Although the relatively small molecular size and the high water solubility of the substance indicates that uptake can take place through aqueous pores, the hydrophilic character of the substance (log Po/w: -3.3) will limit this passive diffusion. Furthermore, the ionization of Formamidopropyldimethylbetain will impair the uptake since compounds need to pass the lipid membranes in the gastrointestinal wall (1). It is therefore unlikely that Formamidopropyldimethylbetain will be absorbed to a high extent from the gastro-intestinal tract. This is supported by the fact, that no substance related adverse effects occured up to the limit dose of 1000 mg/kg bw/day. For risk assessment purposes the oral absorption of Formamidopropyldimethylbetain is set at 10%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor.

Inhalation studies are not available. The high water solubility of Formamidopropyldimethylbetain indicates that the substance will dissolve in the mucus lining of the respiratory tract and subsequently be absorbed through aqueous pores (taking the molecular weight <200 into account). The hydrophilic character of the substance (log Po/w: -3.3) indicates a limited potential for absorption directly across the respiratory tract epithelium. Although it is unlikely that Formamidopropyldimethylbetain will be absorbed to a high extent after inhalation via the lungs, for risk assessment purposes the inhalation absorption of Formamidopropyldimethylbetain is set at 100% as a worst case assumption.

Formation of vapours or inhalable aerosols, particles or droplets at the working place and for the general population can be excluded. Therefore, a DNEL for inhalative exposure appears not warranted.

 

The substance was subjected to a compliance check by ECHA. It was decided that no screening test on reproductive toxicity has to be carried out, but a developmental toxicity study and a 90 day repeated dose toxicity study must be carried out.

A DNEL for fertility and developmental toxicity has not been derived because in the prenatal developmental toxicity study and in the 90 day repeated dose toxicity study there have been no substance related adverse effects up to and including the limit dose of 1000 mg/kg bw/d. Thus it can be assumed that Formamidopropyl¬dimethylbetain has no intrinsic toxic activity relevant to fertility or developmental toxicity by single or repeated oral or dermal exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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

Acute / short-term DNELs - systemic and local effects - have not been derived because Formamidopropyldimethylbetain does not meet the criteria to be classified dangerous for acute toxicity. Furthermore, Formamidopropyldimethylbetain is not classified dangerous for skin/eye irritation/corrosion, skin sensitisation, respiratory irritation/corrosion and respiratory sensitisation.

Long-term DNELs – local effects - have not been derived because Formamidopropyldimethylbetain does not meet the criteria to be classified dangerous for skin/eye irritation/corrosion, skin sensitisation, respiratory irritation/corrosion and respiratory sensitisation.

 

Long-term DNELs – systemic effects:

Formamidopropyldimethylbetain has been tested up to and including the limit dose for repeated dose toxicity testing stipulated in Guideline B.9 and B.26 of Council Regulation (EC) No 440/2008 laying down the test methods pursuant to Regulation (EC) No 1907/2006 (REACH). Since up to and including the limit dose of 1000 mg/kg bw/d, the animals were free of any critical substance related effects, it can be assumed that Formamidopropyl¬dimethylbetain has no intrinsic hazardous toxic activity relevant to humans by single or repeated oral or dermal exposure. Because of this proven absence of intrinsic hazardous activity, Formamidopropyl¬dimethylbetain poses no risk relevant to humans by repeated dermal exposure and a calculation of a corresponding Derived No Effect Level (DNEL) is not appropriate as no NOAEL based on toxic effects could be determined in adequately conducted studies.

In the oral and dermal repeated dose toxicity studies the NOAEL is >= 1000 mg/kg bw/day for male and female rats. A point of departure for the assessment of systemic toxicity after oral and dermal exposure could not be derived due to the lack of substance related critical health effects up to and including the limit dose of the studies design. As an actual value for the NOAEL could not be determined due to limit dose testing in these study types, it could be much higher than 1000 mg/kg bw/day. Formamidopropyldimethylbetain being a substance in solution has the potential to be dermally absorbed. The substance however is expected to be too hydrophilic to cross the lipid rich environment of the stratum corneum (miscible with water; log Po/w: -3.3). As the criteria for 10% dermal absorption as given in the TGD (2) (MW > 500 and log Po/w < -1) are not met, 50% dermal absorption of Formamidopropyldimethylbetain is proposed for risk assessment purposes. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

A 90-day oral repeated-dose study is available.The derivation of a Consumer DNEL long-term oral is not indicated due to the lack of an appropriate point of departure (NOAEL >= 1000 mg/kg bw/d). Although the relatively small molecular size and the high water solubility of the substance indicates that uptake can take place through aqueous pores, the hydrophilic character of the substance (log Po/w: -3.3) will limit this passive diffusion. Furthermore, the ionization of Formamidopropyldimethylbetain will impair the uptake since compounds need to pass the lipid membranes in the gastrointestinal wall (1). It is therefore unlikely that Formamidopropyldimethylbetain will be absorbed to a high extent from the gastro-intestinal tract. This is supported by the fact, that no substance related adverse effects occured up to the limit dose of 1000 mg/kg bw/day. For risk assessment purposes the oral absorption of Formamidopropyldimethylbetain is set at 10%. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor.

Inhalation studies are not available. The high water solubility of Formamidopropyldimethylbetain indicates that the substance will dissolve in the mucus lining of the respiratory tract and subsequently be absorbed through aqueous pores (taking the molecular weight <200 into account). The hydrophilic character of the substance (log Po/w: -3.3) indicates a limited potential for absorption directly across the respiratory tract epithelium. Although it is unlikely that Formamidopropyldimethylbetain will be absorbed to a high extent after inhalation via the lungs, for risk assessment purposes the inhalation absorption of Formamidopropyldimethylbetain is set at 100% as a worst case assumption.

Formation of vapours or inhalable aerosols, particles or droplets at the working place and for the general population can be excluded. Therefore, a DNEL for inhalative exposure appears not warranted.

 

The substance was subjected to a compliance check by ECHA. It was decided that no screening test on reproductive toxicity has to be carried out, but a developmental toxicity study and a 90 day repeated dose toxicity study must be carried out.

A DNEL for fertility and developmental toxicity has not been derived because in the prenatal developmental toxicity study and in the 90 day repeated dose toxicity study there have been no substance related adverse effects up to and including the limit dose of 1000 mg/kg bw/d. Thus it can be assumed that Formamidopropyl¬dimethylbetain has no intrinsic toxic activity relevant to fertility or developmental toxicity by single or repeated oral or dermal exposure.