Table 1.

Regulatory Skin Sensitization Endpoints and Test Methods Accepted for Regulatory Use as of 2017

Region/country	Chemical Sector	Endpointa	Accepted In Vivo Methodsb	Non-animal Alternative Accepted?
Brazil	Cosmetics and Personal Care Products	Hazard	Clinical studiesc LLNAc and its modifications Buehler GPMT	Yes, as part of an integrated strategy
	Pesticides and Plant Protection Products	Hazard	LLNAc and its modifications Buehler GPMT	Yes, as part of an integrated strategy
	Pharmaceuticals	Hazard	Clinical studiesc LLNAc and its modifications Buehler GPMT	Yes, as part of an integrated strategy
Canada	Cosmetics	Riskd	Data submitted upon request only. Results from open literature are acceptable (e.g., LLNA, GPMT, Buehler)	Yes
	Household Products and Art Materials	Riskd	LLNA (preferred if risk assessment is needed) GPMT Buehler	Yes, if animal data are unavailable
	Industrial Chemicals (on Domestic Substances List)	Potency, risk	Data submission not required; Health Canada uses data from accepted methods (LLNA, GPMT, Buehler)	Yes (in voluntary submission)
	Chemicals Not Listed on Domestic Substances List	Potency, risk	LLNAc GPMT Buehler LLNA methods that do not require radiolabeled probes	Considered on a case-by-case basis
	Medical Devices	Hazard	GPMT LLNA	Yes, if validated
	Pesticides	Hazarde	LLNAc GPMT Buehler	Yes, as part of an integrated strategy
	Prescription Pharmaceuticals	Hazard, risk	Not specified	Yes, with justification
	Topical Nonprescription Pharmaceuticals	Hazard	LLNAc GPMT Buehler Clinical studies (e.g., human repeat insult patch test) are preferred for antiseptic drugs	Yes, with justification
	Workplace Chemicals	Hazard, potency	New testing not required; data used must be from humans or accepted animal method (e.g., LLNA, GPMT, Buehler)	Nof
China	Cosmetics	Potency	Buehlerc GPMTc Clinical studies LLNA (optional)	No
	Industrial Chemicals	Hazard, potency, risk	Buehlerc GPMTc LLNA (optional)	No
	Pesticides	Potency	Buehler	No
	Workplace Chemicals	Not specified	Buehler GPMT LLNA	No
European Union	Biocides	Hazard	LLNAc (only required if available data are insufficient) Buehler GPMT	Yes
	Cosmetics	Hazard, potency, risk	Banned (only existing animal data or data generated for other regulatory purposes are accepted)	Yes
	Household Chemicalsg	Hazard, potency, risk	LLNAc Buehler GPMT	Yes; OECD TGs 442C, D, and E are preferred before in vivo testingh
	Industrial Chemicals	Hazard, potency, risk	LLNAc Buehler GPMT	Yes; OECD TGs 442C, D, and Eare preferred before in vivo testingh
	Pharmaceuticals	Hazard	Not specified (method should be justified)	Yes
	Plant Protection Products (i.e. Pesticides)	Hazard	LLNAc, including the reduced LLNA Buehler GPMT	No
	Workplace Chemicalsg	Hazard, potency, risk	LLNAc Buehler GPMT	Yes; OECD TGs 442C, D, and E are preferred before in vivo testingh
Japan	Cosmetics and Personal Care Products	Hazard, potency	GPMT Buehler LLNA	Yes; OECD TG 442C, D and Eh in an integrated strategy (as of January 2018)
	Household Products	Not required	Selected on a case-by-case basis	Undetermined
	Industrial Chemicals	Not required	Selected on a case-by-case basis	Undetermined
	Medical Devices	Hazard, potency, risk	GPMT Buehler LLNA	No
	Pesticides	Hazard	GPMT c Buehler c LLNA	Undetermined
	Pharmaceuticals	Not specified	Not specified	No
	Workplace Chemicals	Not required	Selected on a case-by-case basis	Undetermined
South Korea	Cosmetics	Hazard, risk	Banned (unless justified)	Yes; OECD TG 442C, D, and Eh
	Industrial Chemicals	Hazard, risk	GPMT Buehler Other justified methods	Yes; OECD TG 442C and Dh
	Pesticides	Hazard	LLNA GPMT Buehler Other justified methods	Considered on a case-by-case basis
	Pharmaceuticals	Hazard, potency	GPMTc Adjuvant and Patch test Buehler Draize Freund’s Complete Adjuvant test Open Epicutaneous test Optimization test Split Adjuvant test	No
	Workplace Chemicals	Hazard, risk	Selected on a case-by-case basis	Undetermined
United States	Cosmetics	Not required	Not applicable	Not applicable
	Household Products and Art Materials	Hazard, potency	LLNA and its modifications GPMT Buehler	Considered on a case-by-case basis
	Industrial Chemicals	Hazard, risk	Testing not required	Considered on a case-by-case basis
	Medical Devices	Hazard	GPMTc Buehler test (topical devices only) LLNA (case-by-case)	No
	Pesticides	Hazarde	LLNAc Reduced LLNA GPMT Buehler	Waivers only
	Pharmaceuticals	Potencyi	Not specified	As a screen on a case-by-case basis
	Workplace Chemicals	Hazard, potency	LLNA GPMT Buehler	Yes, if scientifically validated

^aRefers to hazard assessment, potency categorization, or risk assessment

^bOECD test guidelines (or equivalent)

^cPreferred assays

^dSkin sensitization data are typically not required, but risk assessment may be performed for ingredients of concern

^eWhile not a regulatory requirement, a quantitative risk assessment may be conducted on a case-by-case basis

^fThe Hazardous Products Regulation may be revised in the future to allow for the consideration of non-animal data

^gThese sectors are covered by REACH, the industrial chemical legislation in Europe

^hOECD Test Guidelines 442C, D, and E include the DPRA, ARE-Nrf2 Luciferase Test Method, and Human Cell Line Activation Test, respectively

ⁱFDA prefers potency information from human tests