Resinoid of Commiphora erythraea (Burseraceae) obtained from the gum by ethanol extraction

Endpoint summary

Description of key information

Skin irritation/corrosion: Not irritating (OECD 439, GLP, K, rel. 1).

Eye irritation: Irritating, top-down approach:

- ICE: no prediction can be made (OECD 438, GLP, WoE, rel.1)

- EpiOcular: potentially requiring classification and labelling according to the EU CLP (Category 1 or 2) (OECD 492, GLP, WoE, rel.1)

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:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Since no key study was identified on the registered substance, the testing and assessment strategy, as described in ECHA R.7a Endpoint specific guidance (December 2016), was used to evaluate the skin corrosion/irritation potential of the registered substance:

	Element	Information	Conclusion	Comments
Existing data on physico - chemical properties	1a	Is the substance spontaneously flammable in contact with air (pyrophoric) or water at room temperature?	NO
	1b	Is the substance an organic hydroperoxide or an organic peroxide?	NO
	1c	Is the pH of the substance ≤ 2.0 or ≥ 11.5?	NO
	1d	Are there other physical or chemical properties that indicate that the substance is corrosive/irritant?	NO
Existing human data	2	Are there adequate existing human data which provide evidence that the substance is a corrosive or irritant?	NO
Existing animal data from corrosion/irritation studies	3	Are there data from existing studies on corrosion and irritation in laboratory animals, which provide sound conclusive evidence that the substance is a corrosive, irritant or non-irritant?	NO
Existing data from general toxicity studies via the dermal route and from sensitisation studies	4a	Is the substance classified as fatal in contact with skin (LD50 ≤ 50 mg/kg bw, CLP hazard statement H310)	NO
	4b	Has the substance proven to be a corrosive, irritant or non-irritant in a suitable acute dermal toxicity test?	NO
	4c	Has the substance proven to be a corrosive or an irritant in sensitisation studies or after repeated exposure?	NO
Existing/new (Q)SAR data and read -across	5a	Are there structurally related substances (suitable “read-across” or grouping), which are classified as corrosive to the skin (Skin Corrosive Cat. 1), or do suitable (Q)SAR methods indicate corrosion potential of the substance?	NO	Not applicable - UVCB substance
	5b	Are there structurally related substances (suitable “read-across” or grouping), which are classified as irritant to the skin (Skin Irritant Cat. 2), or indicating that the substance is non-irritant, or do suitable (Q)SAR methods indicate irritant or non-irritant potential of the substance?	NO
Existing in vitro data	6a	Has the substance demonstrated corrosive properties in an EU/OECD adopted in vitro test? Data from in vitro test methods that have been validated and are considered scientifically valid but are not yet adopted by EU and/or OECD may also be used if the provisions defined in Annex XI are met	NO
	6b	Has the substance demonstrated irritant or non-irritant properties in an EU/OECD adopted in vitro test? Data from in vitro test methods that have been validated and are considered scientifically valid but are not yet adopted by EU and/or OECD may also be used if the provisions defined in Annex XI are met.	NO	(at the initiation of the dossier, no test was available)
	6c	Are there data from a non-validated suitable in vitro test(s), which provide sound conclusive evidence that the substance is corrosive/ irritant?	NO
Weight-of- Evidence analysis	7	The “elements” described above may be arranged as appropriate. Taking all available existing and relevant data mentioned above (Elements 1-6) into account, is there sufficient information to make a decision on whether classification/labelling is necessary, and –if so –how to classify and label?	NO
New in vitro test for corrosivity	8	Does the substance demonstrate corrosive properties in (an) EU/OECD adopted in vitro test(s) for skin corrosion?	NO
New in vitro test for irritation	9	Does the substance demonstrate irritating or non-irritating properties in (an) EU/OECD adopted in vitro test(s) for skin irritation?	YES	=> an Episkin test for irritation was initiated (Bottom-up strategy - substance expected to be non corrosive). The conclusion of this Episkin test is sufficient to conclude on C&L (viability = 103.1 % <=> Not a skin irritant)
New in vivo test for corrosion/irritation	10	To be used only as a last resort	NO	In vivo testing should not be conducted in this case since the substance falls under the scope of the specific in vitro tests performed, and there are no substance-specific limitations on use of those tests. An adaptation according to Annex XI to the REACH Regulation is included in this dossier.

The in vitro skin irritation study (Envigo, 2016, Rel.1) was performed according to the OECD Guideline 439 and in compliance with GLP, using the EPISKIN reconstructed human epidermis model. The quality criteria required for acceptance of results in the test were satisfied. The relative mean viability of the test item treated tissues was 103.1 %, after the 15‑minute exposure period. With a tissue viability > 50%, the test material was considered to be non-irritant to skin.

Eye irritation:

Since no key study was identified on the registered substance, the testing and assessment strategy, as described in ECHA R.7a Endpoint specific guidance (December 2016), was used to evaluate the eye damage/irritation potential of the registered substance:

	Element	Information	Conclusion	Comments
Conclusion of the information strategy on skin corrosion/irritation	0	Is the substance classified as a skin corrosive?	NO
Existing data on physico - chemical properties	1a	Is the substance spontaneously flammable in contact with air (pyrophoric) or water at room temperature?	NO
	1b	Is the substance an organic hydroperoxide or an organic peroxide?	NO
	1c	Is the pH of the substance ≤ 2.0 or ≥ 11.5?	NO
	1d	Are there other physical or chemical properties that indicate that the substance causes serious eye damage or eye irritation?	NO
Existing human data	2	Are there adequate existing human data which provide evidence that the substance has the potential to cause serious eye damage or eye irritation?	NO
Existing animal data from corrosion/irritation studies	3	Are there data from existing studies on corrosion and irritation in laboratory animals, which provide sound conclusive evidence that the substance is a corrosive, irritant or non-irritant?	NO
Existing/new (Q)SAR data and read-across	4	Are there structurally related substances (suitable “read-across” or grouping), which are classified as causing serious eye damage/eye irritation, or indicating that the substance is non-irritant, or do valid (Q)SAR methods indicate serious eye damage/eye irritation or non-irritation of the substance?	NO	Not applicable - UVCB substance
Existing in vitro data	5a	Has the substance demonstrated serious eye damage, eye irritation or non-irritating properties in an EU/OECD adopted in vitro test? Data from in vitro test methods that have been validated and are considered scientifically valid but are not yet adopted by EU and/or OECD may also be used if the provisions defined in Annex XI are met.	NO
	5b	Are there acceptable data from (a) non-validated suitable in vitro test(s), which provide sound evidence that the substance causes serious eye damage/eye irritation?	NO	(at the initiation of the dossier, no test was available)
Weight-of- Evidence analysis	6	The “elements” described above may be arranged as appropriate. Taking all available existing and relevant data mentioned above (Elements 0 – 5) into account, is there sufficient information to make a decision on whether classification/labelling is necessary, and – if so – how to classify and label?	NO
New in vitro tests for serious eye damage/eye irritation (Annex VII to the REACH Regulation)	7a	Does the substance demonstrate serious eye damage, eye irritation or non-irritant properties in (an) EU/OECD adopted in vitro test(s) for the eye hazard charaterisation? Data from in vitro test methods that have been validated and are considered scientifically valid but are not yet adopted by EU and/or OECD may also be used if the provisions of Annex XI are met.	NO
	8b	Does the substance demonstrate serious eye damage or eye irritant properties in (a) non-validated suitable in vitro test(s) for serious eye damage/eye irritation?	NO	=> an ICE assay was initiated: no prediction can be made => an EpiOcular assay was initiated: potentially requiring classification and labelling (mean percent viability < 60%)
New in vivo test for serious eye damage/eye irritation as a last resort (Annex VIII to the REACH Regulation)	8b	Does the substance demonstrate serious eye damage or eye irritation in an OECD adopted in vivo test?	NO	In vivo testing should not be conducted in this case since the substance is submitted at Annex VII level to the REACH regulation

An ICE assay (Envigo, 2016, Rel.1) was conducted according to the OECD guideline No. 438 and in compliance with GLP. The ocular reactions observed in eyes treated with the test item were:

- maximal mean score of corneal opacity: 1.0, corresponding to the ICE class II;

- mean score of fluorescein retention: 0.5, corresponding to the ICE class I;

- maximal mean corneal swelling: 14.69% corresponding to the ICE class III.

Therefore no prediction can be made according to the combination of the three endpoints. As a consequence, further in vitro testing was conducted following the top-down approach (Scott et al., 2010) to conclude on eye irritation classification.

The EpiOcular test (Envigo, 2017, Rel.1) was conducted according to the OECD guideline No. 492 and in compliance with GLP. The quality criteria required for acceptance of results in the test were satisfied. The tissue viability of the test item was 9.8% after the 6 -hour exposure period. With a percentage of tissue viability < 60%, the test item require classification for eye irritation or eye damage.

Following the top-down approach, taking into account the ICE assay (not eye damage), the EpiOcular assay (not non-classified) and the absence of skin irritation; the substance is considered to be an eye irritant (Scott et al. 2010).

Reference:

Scott L, Eskes C, Hoffmann S, Adriaens E, Alepée N, Bufo M, Clothier R, Facchini D, Faller C, Guest R, Harbell J, Hartung T, Kamp H, Varlet BL, Meloni M, McNamee P, Osborne R, Pape W, Pfannenbecker U, Prinsen M, Seaman C, Spielmann H, Stokes W, Trouba K, Berghe CV, Goethem FV, Vassallo M, Vinardell P and Zuang V (2010) A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom-Up and Top-Down approaches. Toxicol In Vitro 24:1-9.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Based on the available information, the substance should be classified as eye irritant Category 2 (H319: Causes serious eye irritation) according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

No additional self-classification is proposed regarding skin irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

No data was available regarding respiratory irritation.