Registration Dossier

Administrative data

Description of key information

The in vitro skin irritation study (EpiDerm, BASF 2013) and the in vivo study with rabbits (Bioassay 2014) indicated that the read-across substance is not or mildly skin irritating.
Both in vitro eye irritation studies (EpiOcular and BCOP, BASF 2013) and the in vivo study (Bioassay 2014) with the read-across substance demonstrated negative results.
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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

Due to a lack of experiments with the test substance and the existence of a structural analog (read-across substance) part of or the complete data was derived from the read-across substance. For details on the read-across reliability please refer to IUCLID Section 13. 

 

Skin irritation in vitro

The potential of the read-across substance Bis(2-propylheptyl) hexanedioate to cause dermal corrosion/irritation was assessed in a reconstructed three dimensional human epidermis model (EpiDerm) (BASF SE, 2013). A single topical application of 50 µL (corrosion test) or 30 µL (irritation test) of the undiluted read-across substance was used. De-ionized water served as negative control in the corrosion test and PBS in the irritation test. As positive control 8 -n potassium hydroxide solution was used in the corrosion test and 5% (w/v) sodium dodecyl sulfate (SDS) in the irritation test. For the corrosion test two EpiDerm tissue samples were incubated with the read-across substance for 3 minutes and 1 hour, respectively. The irritation test was performed with three EpiDerm tissue samples, which were incubated with the read-across substance for 1 hour followed by a 42-hours post incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MMT) was chosen as endpoint. The formazan production of the read-across substance treated epidermal tissues was compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability. The read-across substance was not able to reduce MTT directly. In the corrosive test the mean viability of the read-across substance treated tissues determined after an exposure period of 3 minutes was 97 %, and it was 103 % after an exposure period of 1 hour. The irritation test revealed a mean viability of ther read-across substance treated tissues of 103 % after an exposure period of 1 hour with about 42 hours post-incubation. The read-across substance did not show a skin irritation potential in the EpiDerm skin corrosion/irritation test under the test conditions chosen.

 

Skin irritation in vivo

The read-across substance Bis(2-propylheptyl) hexanedioate was tested in a skin irritation/corrosion study in the rabbit according to OECD guideline no. 404 (Bioassay 2014). Three female rabbits were exposed to 0.5 mL of the undiluted read-across substance, applied onto shaved skin for 4 hours using a semi-occlusive dressing. Observations for erythema and edema were made 0 and 1h after removal of the test patches and 24, 48, 72 h after the beginning of application and were deduced according to the scoring system of Draize. Clinical observation revealed very slight to well-defined erythema (grade 1 -2) and very slight edema (grade 1) which were fully reversible within 7 days. The read-across substance was considered to show a mild skin irritation potential which was not sufficient for classification.

 

Conclusion skin irritation

The in vitro skin irritation study (EpiDerm, BASF 2013) and the in vivo study with rabbits (Bioassay 2014) indicated that the read-across substance is not or mildly skin irritating not sufficient for classification.

 

Eye irritation in vitro

The eye irritation properties of the read-across substance Bis(2-propylheptyl) hexanedioate were examined in vitro by means of the BCOP assay using fresh bovine cornea (BASE SE, 2013; 63V0814/12A528). Each treatment group (undiluted liquid read-across substance, de-ionized water as negative control and 1 % (w/v) solution of sodium hydroxide as positive control) consisted of 3 corneas. 750 µL test solution was applied into the anterior chamber of a specially designed cornea holders and the corneas were incubated in a horizontal position at about 32 °C for approximately 10 minutes followed by a 2 hours post-incubation period. Corneal opacity was measured quantitatively as the amount of light transmission through the cornea. The control groups were treated in the same manner. Permeability was measured quantitatively as the amount of sodium fluorescein dye that passes across the full thickness of the cornea. Both measurements were used to calculate an In Vitro Irritancy Score (IVIS) of the test substance relative to the control corneas. The positive control showed clear opacity effects corresponding to a classification as corrosive / severe irritant to the eye (IVIS: 177.5). Relative to the negative control, the read-across substance did not cause any increase of the corneal opacity or permeability. The calculated mean IVIS was 1.5 and thus the read-across substance did not cause ocular or severe irritation in the BCOP Test under the test conditions chosen.

In a second in vitro test the eye irritation potential of the read-across substance Bis(2-propylheptyl) hexanedioate was tested using the EpiOcular assay (BASF SE, 2013; 62V0814/12A527). Two EpiOcular tissue samples were incubated with the read-across substance, the negative control (de-ionized water) and the positive control (Methylacetate) for 30 minutes followed by a 2-hours post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the read-across substance treated epidermal tissues is compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability. The mean tissue viability of the positive control was 33 % indicating the appropriate sensitivity of the test system. The read-across substance was not able to reduce MTT directly. The mean viability of the read-across substance treated tissues was 100 %. Based on the observed results it was concluded that the read-across substance does not show an eye irritation potential in vitro.

 

Eye irritation in vivo

An in vivo eye irritation study (OECD 405, Bioassay 2014) was conducted the read-across substance Bis(2-propylheptyl) hexanedioate using three female rabbits. A volume of 0.1 mL of the undiluted read-across substance was applied in the conjuctival sac of one eyelid of each rabbit. The read-across substance was washed out and the untreated eye served as control. After 1, 24, 48, 72 and 96 hours the rabbit eyes were examined and the effects were scored according to the scoring system of Draize. The cornea, iris, conjunctiva and chemosis score (mean of 24, 48 and 72 h) did not show an effects in any test animal and the read-across substance was demonstrated to be not an eye irritant. 

 

Conclusion eye irritation

Both in vitro eye irritation studies (EpiOcular and BCOP, BASF 2013) and the in vivo study (Bioassay 2014) with the read-across substance demonstrated negative results.


Justification for selection of skin irritation / corrosion endpoint:
GLP guideline study with a read-across substance supported by further studies

Justification for selection of eye irritation endpoint:
GLP guideline study with a read-across substance supported by further studies

Justification for classification or non-classification

Based on the available data the read-across substance does not have to be classified for skin or eye irritation according to Regulation (EC) No 1272/2008 (CLP/GHS) as amended for the seventh time in Regulation (EC) No 2015/1221.