Methodological limitations and confounders in dermal toxicity evaluation of aqueous test substance by OECD technical guidelines 402, 410: our experience of testing ethanol based hand sanitizer.

BACKGROUND

In view of overzealous use of Alcohol based hand sanitizer (ABHS) during COVID-19 pandemic and associated alarming rise in the cases of hand eczema and dermatitis around the world. We conducted an dermal toxicity with objective of exploring the acute and subacute effects of ethanol based hand sanitizer (EBHS) on Sprague Dawley rats.

AIMS

To evaluate acute and subacute dermal toxicity due to ethanol based hand sanitizer (EBHS) on Sprague Dawley rats.

METHODS

In first phase, following Organisation for Economic Co-operation and Development (OECD) Technical Guidelines (TG) 402, we conducted acute dermal toxicity study with two rats and EBHS containing 72.34% ethanol. In second phase, sub-acute dermal toxicity study was conducted, following OECD TG 410 with five groups of rats (10 animals of either sexes in each group) at various doses.

RESULTS

In both the studies, no erythema, oedema, and eschar was observed. Although no clinical signs of toxicity were observed in both the studies, one death was encountered in subacute study. Macroscopically skin was normal; however, microscopic changes such as hyperkeratosis, parakeratosis, erosion, and extracellular oedema in epidermis and diffuse inflammatory cell infiltration in dermis was observed, suggestive of spongiotic dermatitis and 'clinic-pathological discordance'. However, attributing this changes to ethanol is difficult due to methodological limitations and confounders.

CONCLUSION

In both the studies, ethanol based hand sanitizer (EBHS) was found to be non-irritant with LD of > 2000 mg/kg and classified as Class 5/Unclassified according to GHS classification. Although, spongiotic changes were observed, methodological limitation of absence of control group in TG 402 and confounding effect of water and occlusion in all the animals/groups in both studies prevented us to attribute it to ethanol.