Fatty acids, tall-oil, reaction products with maleic anhydride and triethylenetetramine

Endpoint summary

Description of key information

The repeated administration in the repeated dose toxicity combined with reproductive endpoint study in rodent by oral application did not show any adverse systemic effects. NOAEL for systemic effects is considered to be 1000 mg/kg bw/day for males and females. Local effect were seen in lungs but considered an indirect effect due to suspected chemical pneumonitis. It is known that low viscosity chemicals can generate residues in the esophagus that can be aspired in the trachea and deposited in lungs creating such local inflammation as seen in the study. Dark material (the test material) seen in some animals in lung histiocytes do support such a conclusion.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance Fatty acids, tall-oil, reaction products with maleic anhydride and triethylene-tetramine (TOFA-MA-TETA) and the source substance Fatty acids, tall-oil, reaction products with di-ethylenetriamine (DETA), maleic anhydride, tetraethylenepentamine (TEPA) and triethylenetetramine (TETA) are characterised by the same starting materials: the hydrophobic part from fatty acids and the hydrophilic part from the polyethyleneamines.
The source substance is a mixture of ethyleneamines of different lengths (DETA, TETA and TEPA). The target substance contains only one ethyleneamine: TETA.
The source and the target substance show therefore the same reactive groups and a similar composition with the absence of two original ethyleneamines (DETA and TEPA) as biggest difference. A read-across to the source is therefore justified.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance actually is manufactured from the same starting materials of the source:
Fatty acids, tall-oil and maleic anhydride. TOFA is reacted with maleic anhydride to make a Diels-Alder intermediate which is a tri-acid. This is reacted with the TETA to produce a mixture of amido-amine & oligomeric UVCB constituents. The source substance also contains two other ethyleneamines: di-ethylenetriamine and tetraethylenepentamine.
The source substance has been registered already and based on the pathological evaluation, a No-Observed-Effect-Level (NOEL) could not be determined in the study submitted. The same conclusion is applied to the target substance.

3. ANALOGUE APPROACH JUSTIFICATION
The target substance is one of the constituent of the UVCB source substance and thus read-across from the bigger compound Fatty acids, tall-oil, reaction products with diethylenetriamine, maleic anhydride, tetraethylenepentamine and triethylenetetramine to TOFA-MA-TETA is common practice and justified.

4. DATA MATRIX
Whereas the source substance is a Fatty acids, tall-oil, reaction products with di-ethylenetriamine (DETA), maleic anhydride, tetraethylenepentamine (TEPA) and triethylenetetramine (TETA), hence using a mixture of DETA, TETA and TEPA as reactant, the target substance uses pure TETA (triethylenetetramine) instead, being a more purified (narrower cut distillation) form of DETA/TETA/TEPA resulting in a name change of the target substance, being Fatty acids, tall-oil, reaction products with maleic anhydride and triethylenetetramine (TETA).

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Dose descriptor:

NOEL

Remarks on result:

not determinable

Dose descriptor:

LOAEL

Effect level:

<= 300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Remarks on result:

other: NOAEL for systemic toxicty

Critical effects observed:

not specified

Conclusions:

In an OECD 422 study with the source substance fatty acids, tall oil, reaction products with diethylenetriamine, maleic anhydride, tetraethylenepentamine and triethylenetetramine test item-related histopathological changes were restricted to the lung, considered local but not systemic effects. No other findings were seen. Multifocal subacute bronchopneumonia, characterized by peribronchial foci of prominent fibrosis, with re-epithelialization, infiltration with mononuclear cells, histiocytes and occasional multinucleated cells, was observed in a small proportion of treated males and females of all dose groups, without any dose relationship. In addition, a mild amount of intrahistiocytic black material was seen in the lung of one male treated at 300 or and one male at 1000 mg/kg/day.
As a conclusion, based on the pathological evaluation, a No-Observed-Effect-Level (NOEL) could not be determined in this study, but a NOAEL for systemic toxicity was set to 1000 mg/kg bw/d.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In absence of systemic toxicity seen in the OECD 422 study in rats, the substance is not subject to classification for systemic target organ toxicity, repeat exposure, according to CLP (Regulation EC No 1272/2008).