Fatty acids, tall-oil, reaction products with 2-[(2-aminoethyl)amino]ethanol

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: expert report

Adequacy of study:

key study

Conclusions:

Based on all available information no final conclusion on a bioaccumulation potential can be drawn but there is no evidence that 400112 would have an accumulation potential.

Executive summary:

The substance 400112 is a complex mixture of components (UVCB), it is liquid at room temperature. In the following table some physical-chemical properties of 400112 are listed:

 

Molecular weight:  348 – 614 Da

Water solubility:  < 0.1 mg/L

Boiling point:  substance decomposes before boiling

Log Pow:  > 6

Vapour pressure:  1.1 x 10-5 Pa at 25°C

 

The available physical-chemical information of the substance has been evaluated in combination with results from toxicological studies to assess the toxicokinetic behaviour. The ECHA “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance 2017” document provides guidance, which physical-chemical properties commonly determine dermal, oral and respiratory absorption, distribution, metabolism and elimination of substances.

 

Dermal absorption

 

The substance 400112 is a complex mixture of components with a broad range of molecular weight distribution. Molecules with MW < 500 Da may be absorbed through the skin. However, the low water solubility and the lipophilic properties of the substance (log Pow > 6) are expected to limit absorption across the skin.

Due to its skin irritation potential that led to scab of rat skin in the acute dermal toxicity study (24 hours occlusive exposure) damage of the skin surface may enhance penetration. However, no systemic toxic effects were observed in this dermal toxicity study.

 

Oral absorption

 

The low water solubility and the lipophilic properties of the substance 400112 are expected to limit its absorption in the digestive tract. In the repeated dose study (OECD 421) with oral gavage dosing at 20, 60, and 200 mg/kg/d several animals died after 11 to 41 days of continuous exposure at 60 or 200 mg/kg/d. Systemic toxic effects were not observed in these and all surviving animals. Lesions in the stomach and gastrointestinal tract were observed in dead animals very likely being the reason of death. In all surviving animals no lesions were observed at scheduled necropsy.

From these results no conclusion can be drawn on absorption of 400112 after oral exposure. In any case the surface active / corrosive properties of the substance led to severe local effects in the gastrointestinal tract very likely causing death of several animals at repeated oral doses of 60 or 200 mg/kg/d. The substance 400112 is classified STOT RE 2 after oral exposure.

 

Respiratory absorption

 

The substance 400112 has a very low vapour pressure and decomposes before boiling. In addition, the substance is a viscous liquid and thus formation of inhalable aerosols is rather unlikely. Accordingly, inhalation is an unlikely route of human exposure.

 

Distribution and metabolism

 

There is no information available on distribution and metabolism of 400112 in the available studies.

 

Excretion

 

There is no information available on excretion of 400112 in the available studies.

 

Bioaccumulation potential

 

Based on all available information no final conclusion on a bioaccumulation potential can be drawn but there is no evidence that 400112 would have an accumulation potential.

In the sub-chronic oral toxicity study in rats (OECD 408) at doses of 5, 15, and 45 mg/kg body weight/day one animal (1/30) of the high dose group died after 78 days of exposure. This death was considered treatment related; the reason for death is not known. In all surviving animals including high dose animals no local and no systemic adverse effects were observed. In another repeat dose oral toxicity study (OECD 421) with doses of 20, 60, and 200 mg/kg/d, at 60 mg/kg/d 3/24 animals and at 200 mg/kg/d 7/24 animals died between treatment days 11 to 41. In almost all dead animals lesions of the stomach and/or gastrointestinal tract were observed. Based on the surface active / corrosive properties of 400112 it is rather likely that the local effect on the intestines was the reason for the death of animals. In animals surviving until scheduled end of the study no systemic or local toxic effects were observed.

The result of the sub-chronic toxicity study provides evidence that 400112 very likely does not have an accumulation potential. Otherwise, it could be expected that after daily dosing for 90 days 400112 would accumulate in certain tissues reaching concentrations that would exhibit corrosive or at least irritating effects. However, no such effects were observed.

Additional information

The substance 400112 is a complex mixture of components (UVCB), it is liquid at room temperature. In the following table some physical-chemical properties of 400112 are listed:

 

Molecular weight:  348 – 614 Da

Water solubility:  < 0.1 mg/L

Boiling point:  substance decomposes before boiling

Log Pow:  > 6

Vapour pressure:  1.1 x 10-5 Pa at 25°C

 

The available physical-chemical information of the substance has been evaluated in combination with results from toxicological studies to assess the toxicokinetic behaviour. The ECHA “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance 2017” document provides guidance, which physical-chemical properties commonly determine dermal, oral and respiratory absorption, distribution, metabolism and elimination of substances.

 

Dermal absorption

 

The substance 400112 is a complex mixture of components with a broad range of molecular weight distribution. Molecules with MW < 500 Da may be absorbed through the skin. However, the low water solubility and the lipophilic properties of the substance (log Pow > 6) are expected to limit absorption across the skin.

Due to its skin irritation potential that led to scab of rat skin in the acute dermal toxicity study (24 hours occlusive exposure) damage of the skin surface may enhance penetration. However, no systemic toxic effects were observed in this dermal toxicity study.

 

Oral absorption

 

The low water solubility and the lipophilic properties of the substance 400112 are expected to limit its absorption in the digestive tract. In the repeated dose study (OECD 421) with oral gavage dosing at 20, 60, and 200 mg/kg/d several animals died after 11 to 41 days of continuous exposure at 60 or 200 mg/kg/d. Systemic toxic effects were not observed in these and all surviving animals. Lesions in the stomach and gastrointestinal tract were observed in dead animals very likely being the reason of death. In all surviving animals no lesions were observed at scheduled necropsy.

From these results no conclusion can be drawn on absorption of 400112 after oral exposure. In any case the surface active / corrosive properties of the substance led to severe local effects in the gastrointestinal tract very likely causing death of several animals at repeated oral doses of 60 or 200 mg/kg/d. The substance 400112 is classified STOT RE 2 after oral exposure.

 

Respiratory absorption

 

The substance 400112 has a very low vapour pressure and decomposes before boiling. In addition, the substance is a viscous liquid and thus formation of inhalable aerosols is rather unlikely. Accordingly, inhalation is an unlikely route of human exposure.

 

Distribution and metabolism

 

There is no information available on distribution and metabolism of 400112 in the available studies.

 

Excretion

 

There is no information available on excretion of 400112 in the available studies.

 

Bioaccumulation potential

 

Based on all available information no final conclusion on a bioaccumulation potential can be drawn but there is no evidence that 400112 would have an accumulation potential.

In the sub-chronic oral toxicity study in rats (OECD 408) at doses of 5, 15, and 45 mg/kg body weight/day one animal (1/30) of the high dose group died after 78 days of exposure. This death was considered treatment related; the reason for death is not known. In all surviving animals including high dose animals no local and no systemic adverse effects were observed. In another repeat dose oral toxicity study (OECD 421) with doses of 20, 60, and 200 mg/kg/d, at 60 mg/kg/d 3/24 animals and at 200 mg/kg/d 7/24 animals died between treatment days 11 to 41. In almost all dead animals lesions of the stomach and/or gastrointestinal tract were observed. Based on the surface active / corrosive properties of 400112 it is rather likely that the local effect on the intestines was the reason for the death of animals. In animals surviving until scheduled end of the study no systemic or local toxic effects were observed.

The result of the sub-chronic toxicity study provides evidence that 400112 very likely does not have an accumulation potential. Otherwise, it could be expected that after daily dosing for 90 days 400112 would accumulate in certain tissues reaching concentrations that would exhibit corrosive or at least irritating effects. However, no such effects were observed.