Reaction products of tetraethylenepentamine and maleic anhydride

Endpoint summary

Description of key information

Skin corrosion:
A K1, GLP-compliant in vitro skin corrosion study was performed according to OECD guideline 431 and EU Method B.40 (K1, Warren, 2014b). The substance was considered not to be classified for skin corrosion.
  

Skin irritation
A K1, GLP-compliant in vitro skin irritation study was performed according to OECD guideline 439 and EU Method B.46 (K1, Warren, 2014a). The substance was considered not to be classified for skin irritation.

Eye irritation:
A K1, GLP-compliant eye irritation study was performed according to OECD guideline 437 (K1, Warren, 2015). The substance was considered not irritant to eyes and should not be classified for eye irritation. 

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In vitro skin irritation:

Warren (2014a) studied skin irritation using the EPISKIN ^TM reconstructed human epidermis model in a K1, GLP compliant study. The substance was applied topically to triplicate tissues for an exposure period of 15 minutes. 10 µl (26.3 µl/cm²) of the test item (undiluted) was applied to the epidermis surface. The cell viability was determined by mitochondrial dehydrogenase activity, assessed by the reduction of MTT to a soluble, coloured, formazan product. The prediction model uses the percentage viability values (compared to negative control viability) to identify irritant and non-irritant substances. The relative mean viability of the test item treated tissues was 90.4% after a 15-minute exposure period and 42 hours post-exposure incubation period. The substance is considered not to be classified for skin irritation.

In vitro skin corrosion:

Warren (2014b) studied skin corrosion using the EPISKIN^TM reconstructed human epidermis model. Duplicate tissues were treated with the substance for exposure periods of 3, 60 and 240 minutes. 50 µl of the test item was applied topically. The cell viability was determined by mitochondrial dehydrogenase activity, assessed by the reduction of MTT to a soluble, coloured, formazan product. The optical density was measured (quantitative viability analysis) at 562 nm (without a reference filter). The corrosivity potential of the test item was predicted form the relative mean tissue viabilities obtained after the 3, 60 and 240 -minute exposure periods, compared to the mean of the negative control tissues treated with 0.9% w/v sodium chloride solution. The relative mean viabilities of the test item treated tissues were:

- 240 minutes exposure: 108.1%;

- 60 minutes exposure: 143.9%;

- 3 minutes exposure: 129.1%.

The substance is considered not to be classified for skin corrosion.

Eye irritation:

Warren (2015) investigated eye irritation by an in vitro bovine corneal opacity-permeability (BCOP) assay (K1, GLP). 0.75 ml of the substance (as supplied) was applied for 10 minutes followed by an incubation period of 120 minutes. Both opacity and permeability were measured and the resulting objective values were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS). The corneas treated with the test item were clear post treatment and post incubation. An in vitro irritancy score of 0.9 was calculated. Based on the results (IVIS < 3), the substance is considered not irritant to eyes and should not be classified for eye irritation.

In vivo skin irritation

A key study is available for acute dermal toxicity. LD50 was determined in this study to be >2000 mg/kg bw (based on active ingredient). According to the REACH Regulation, no in vivo skin irritation study needs to be conducted if the key acute dermal toxicity study does not indicate skin irritation up to the limit dose level (2000 mg/kg bw) (column 2, annex VIII, section 8.1.1). In addition, the results of the in vitro skin irritation test (K1, GLP, Warren, 2014) showed a relative mean viability of test item treated tissues of 90.4% after 15 min exposure period and 42 h post-exposure incubation period. Therefore, it is not necessary to perform an in vivo skin irritation study with the substance.

In vivo eye irritation

A key in vitro eye irritation study (BCOP) is available. The test item is considered not to be classified (IVIS score < 3) for eye irritation. Based on the OECD TG 437 guideline, no in vivo eye irritation study is required for the substance.

Justification for selection of skin irritation / corrosion endpoint:
Reliable skin irritation study

Justification for selection of eye irritation endpoint:
Only one reliable study is available.

Justification for classification or non-classification

Based on the results of the skin irritation/corrosion and eye irritation studies and according to the criteria of the CLP Regulation, the substance should not be classified for skin irritation/corrosion and eye irritation.