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During the discussions at the fifty-fourth session on the revision of paragraph 2.8.3.2, the following observations were made: (a) A substance or mixture resulting as non-classified based on OECD Test Guideline (TG) No 439 "In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method" may also be considered as non-corrosive to skin for the purposes of these Regulations without further new testing. (...) ST/SG/AC.10/C.3/2019/1 3 1 OECD Guideline for the testing of chemicals No. 404 "Acute Dermal irritation/Corrosion" 2015 2 OECD Guideline for the testing of chemicals No. 435 "In Vitro Membrane Barrier Test Method for Skin Corrosion" 2015 3 OECD Guideline for the testing of chemicals No. 431 "In Vitro Skin Corrosion: reconstructed human epidermis (RHE) test method" 2016 4 OECD Guideline for the testing of chemicals No. 430 "In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER)" 2015 5 OECD Guideline for the testing of chemicals No. 439 "In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method" 2015 Proposal 2 6. (...) If the in vitro test results indicate that the substance or mixture is corrosive, but the test method does not allow discrimination between packing groups I, II and III, it shall be considered to be packing group I.” 1 OECD Guidelines for the testing of chemicals No. 404 "Acute Dermal irritation/Corrosion" 2015; No. 435 "In Vitro Membrane Barrier Test Method for Skin Corrosion" 2015; No. 431 "In Vitro Skin Corrosion: reconstructed human epidermis (RHE) test method" 2016; and No. 430 "In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER)" 2015 2 OECD Guideline for the testing of chemicals No. 439 "In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method" 2015

OECD Test Guideline (TG) 431 "In vitro Skin Corrosion: Human Skin Model Test" was updated to introduce sub-categorisation for skin corrosion and adopted by the OECD in 2013 and further revised in 2014, 2015 and 2016, as TG 431 "In vitro skin corrosion: reconstructed human epidermis (RHE) test method". The in vitro methods included in TG 431 can now discriminate between GHS sub-category 1A and sub-category 1B/C. (...) The categorisation referred to is based on the classification criteria set out in the GHS, Rev. 7 (Table 3.2.1): Criteria Category 1 Destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least one tested animal after exposure ≤ 4 h Sub-category 1A Corrosive responses in at least one animal following exposure ≤ 3 min during an observation period ≤ 1 h Sub-category 1B Corrosive responses in at least one animal following exposure > 3 min and ≤ 1 h and observations ≤ 14 days Sub-category 1C Corrosive responses in at least one animal after exposures > 1 h and ≤ 4 h and observations ≤ 14 days 4. (...) A substance or mixture which is determined not to be corrosive in accordance with OECD Test Guideline 4303 4 or 4314 may be considered not to be corrosive to skin for the purposes of these Regulations without further testing. 1 OECD Guideline for the testing of chemicals No. 404 "Acute Dermal Irritation/Corrosion" 2015 2 OECD Guideline for the testing of chemicals No. 435 "In Vitro Membrane Barrier Test Method for Skin Corrosion" 2015 3 OECD Guideline for the testing of chemicals No. 431 "In Vitro Skin Corrosion: reconstructed human epidermis (RHE) test method" 2016 34 OECD Guideline for the testing of chemicals No. 430 "In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER)" 2015 4 OECD Guideline for the testing of chemicals No. 431 "In Vitro Skin Corrosion: Human Skin Model Test" 2015”.

Table 3.2.1 Replace with the following: "Table 3.2.1 Skin corrosion category and sub-categories a Criteria Category 1 Destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least one tested animal after exposure ≤ 4 h Sub-category 1A Corrosive responses in at least one animal following exposure ≤ 3 min during an observation period ≤ 1 h Sub-category 1B Corrosive responses in at least one animal following exposure 3 min and ≤ 1 h and observations ≤ 14 days Sub-category 1C Corrosive responses in at least one animal after exposures 1 h and ≤ 4 h and observations ≤ 14 days “a The use of human data is addressed in 3.2.2.2 and in chapters 1.1 (para. 1.1.2.5(c)), and 1.3 (para. 1.3.2.4.7).” 3.2.2.1.2 Former 3.2.2.5 becomes new 3.2.2.1.2. (...) An example of a validated internationally accepted in vitro test method for skin irritation is OECD Test Guideline 439 (Reconstructed Human Epidermis Test Method); e Measurement of pH alone may be adequate, but assessment of acid or alkali reserve (buffering capacity) would be preferable. (...) Category 2 Warning Yes No 12 ST/SG/AC.10/C.4/2012/12 3.2.5.3.3 In the case of a study with 6 animals the following principles apply: (a) The substance or mixture is classified as skin corrosion Category 1 if destruction of skin tissue (that is, visible necrosis through the epidermis and into the dermis) occurs in at least one animal after exposure up to 4 hours in duration; (b) The substance or mixture is classified as skin irritation Category 2 if at least 4 out of 6 animals show a mean score per animal of ≥ 2.3 and ≤ 4.0 for erythema/eschar or for oedema; (c) The substance or mixture is classified as skin irritation Category 3 if at least 4 out of 6 animals show a mean score per animal of ≥ 1.5 and 2.3 for erythema/eschar or for oedema. 3.2.5.3.4 In the case of a study with 5 animals the following principles apply: (a) The substance or mixture is classified as skin corrosion Category 1 if destruction of skin tissue (that is, visible necrosis through the epidermis and into the dermis) occurs in at least one animal after exposure up to 4 hours in duration; (b) The substance or mixture is classified as skin irritation Category 2 if at least 3 out of 5 animals show a mean score per animal of ≥ 2.3 and ≤ 4.0 for erythema/eschar or for oedema; (c) The substance or mixture is classified as skin irritation Category 3 if at least 3 out of 5 animals show a mean score per animal of ≥ 1.5 and 2.3 for erythema/eschar or for oedema. 3.2.5.3.5 In the case of a study with 4 animals the following principles apply: (a) The substance or mixture is classified as skin corrosion Category 1 if destruction of skin tissue (that is, visible necrosis through the epidermis and into the dermis) occurs in at least one animal after exposure up to 4 hours in duration; (b) The substance or mixture is classified as skin irritation Category 2 if at least 3 out of 4 animals show a mean score per animal of ≥ 2.3 and ≤ 4.0 for erythema/eschar or for oedema; (c) The substance or mixture is classified as skin irritation Category 3 if at least 3 out of 4 animals show a mean score per animal of ≥ 1.5 and 2.3 for erythema/eschar or for oedema.” 13

The text as amended in accordance with the editorial changes which were subsequently proposed by the informal working group on the revision of Chapters 3.2 and 3.3 is reproduced in document ST/SG/AC.10/C.4/2012/12 for consideration by the Sub-Committee. 5 ST/SG/AC.10/C.4/2012/29 3.2.5.3.3 In the case of a study with 6 animals the following principles apply: (a) The substance or mixture is classified as skin corrosion Category 1 if destruction of skin tissue (that is, visible necrosis through the epidermis and into the dermis) occurs in at least one animal after exposure up to 4 hours in duration; (b) The substance or mixture is classified as skin irritation Category 2 if at least 4 out of 6 animals show a mean score per animal of ≥ 2.3 ≤ 4.0 for erythema/eschar or for oedema; (c) The substance or mixture is classified as skin irritation Category 3 if at least 4 out of 6 animals show a mean score per animal of ≥ 1.5 2.3 for erythema/eschar or for oedema. 3.2.5.3.4 In the case of a study with 5 animals the following principles apply: (a) The substance or mixture is classified as skin corrosion Category 1 if destruction of skin tissue (that is, visible necrosis through the epidermis and into the dermis) occurs in at least one animal after exposure up to 4 hours in duration; (b) The substance or mixture is classified as skin irritation Category 2 if at least 3 out of 5 animals show a mean score per animal of ≥ 2.3 ≤ 4.0 for erythema/eschar or for oedema; (c) The substance or mixture is classified as skin irritation Category 3 if at least 3 out of 5 animals show a mean score per animal of ≥ 1.5 2.3 for erythema/eschar or for oedema. 3.2.5.3.5 In the case of a study with 4 animals the following principles apply: (a) The substance or mixture is classified as skin corrosion Category 1 if destruction of skin tissue (that is, visible necrosis through the epidermis and into the dermis) occurs in at least one animal after exposure up to 4 hours in duration; (b) The substance or mixture is classified as skin irritation Category 2 if at least 3 out of 4 animals show a mean score per animal of ≥ 2.3 ≤ 4.0 for erythema/eschar or for oedema; (c) The substance or mixture is classified as skin irritation Category 3 if at least 3 out of 4 animals show a mean score per animal of ≥ 1.5 2.3 for erythema/eschar or for oedema.”.]

Is a ‘response’ a full corrosive response as defined by “produces destruction of skin tissue, namely visible necrosis through the epidermis and into the dermis” or is any response (including a partial response) acceptable? (d) The definition of ‘skin’ in the Orange Book is not very clear as it can mean epidermis, dermis or both. The definition should be clarified. 3.

Criteria in the GHS (Rev.5): Table 3.2.1: Skin corrosion category and sub-categories Criteria Category 1 Destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least one tested animal after exposure ≤ 4 h Sub-category 1A Corrosive responses in at least one animal following exposure ≤ 3 min during an observation period ≤ 1 h Sub-category 1B Corrosive responses in at least one animal following exposure 3 min and ≤ 1 h and observations ≤ 14 days Sub-category 1C Corrosive responses in at least one animal after exposures 1 h and ≤ 4 h and observations ≤ 14 days 5. (...) Criteria in the GHS (Rev.5): Table 3.2.1: Skin corrosion category and sub-categories Criteria Category 1 Destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least one tested animal after exposure ≤ 4 h Sub-category 1A Corrosive responses in at least one animal following exposure ≤ 3 min during an observation period ≤ 1 h Sub-category 1B Corrosive responses in at least one animal following exposure 3 min and ≤ 1 h and observations ≤ 14 days or following exposure ≤ 3 min and observations 1h ≤ 14 days Sub-category 1C Corrosive responses in at least one animal after exposures 1 h and ≤ 4 h and observations ≤ 14 days 15.

GE.01-32673 (E) TR A D E/W P.7/G E.6/2002/8 page 2 Disease French name Causative agent Pathogen Optimal temperature Transmission/Survival Symptoms - vegetation Symptoms - tubers Action FUNGUS Black dot Dartrose Colletotrichum coccodes Fungus 25° - 30° C Plant residue from potatoes and tomatoes Warm summers: yellowing, curling up and withering of the leaves and stem, and (a typical symptom of early destruction of the roots) sloughing of the epidermis of the roots and formation of numerous black dots Microsclerotia with cilia Healthy seedlings and rotation Dry rot Fusariose Fusarium roseum var. sambucinum, Fusarium solani var. coeruleum Fungus 15° - 25° C Primary inoculum in soil and tuber Dry rot Avoid harvesting more than three weeks after vine-killing, treat with a fungicide containing imazalil and thiabendazole Silver scurf Gale argentée Helminthosporium solani Fungus 20° - 25° C Contaminated tubers. (...) Characteristic white mildew-like growth on underside of leaves Mottled reddish-brown areas on the surface that may extend from the epidermis to the centre of the tuber Copper-based fungicides (risk of phytotoxicity), contact fungicides (maneb, mancozeb), penetrating fungicides (cymoxanil) or systemic pesticides (metalaxyl, oxadixyl) TR A D E/W P.7/G E.6/2002/8 page 3 Verticillium wilt Verticilliose Verticillium alboatrum and V. dahliae Fungus Inoculum borne in soil and in irrigation and run-off water Yellowing of the leaves (sometmes on only one side of the plant), followed by overall withering of the leaves.

The chest exhibits lesions with separation of the epidermis. Detachment of the skin on the face in several areas. (...) Kazem Maydabadi, age 19. j Denudation of epidermis on face. Skin completely detached from testicles. (...) Erythema and blisters on the hand. Dsnudation of the epidermis on the face, trunk and arms. Leucocyte count 2,100. 31.