Table 1.
Overview of Each Chemical-Exposure Scenario and Associated Risk Classifications
| Compound | Use Scenario | Risk Classification | Risk Classification Reasoning | Reference |
|---|---|---|---|---|
| Paraquat dichloride | Oral 35 mg/kg ingestion (poisoning) | High risk | The minimum oral human lethal dose is 35 mg/kg/day. Paraquat poisoning leads to multiorgan failure with specific pulmonary edema and fibrosis. | WHO, 1984; Bertram et al., 2013 |
| Rosiglitazone | Oral 8 mg/day | High risk | The maximum recommended daily dose for the treatment of diabetes is 8 mg/day. Rosiglitazone leads to adverse effects such as weight gain, anemia, fluid retention, and adverse effects on lipids. Importantly, fluid retention may exacerbate or lead to heart failure and other effects. A low dose of 2 mg/day shows some efficacy. | Wolffenbuttel et al., 2000; Yki-Järvinen, 2004 |
| Oral 2 mg/day | High risk | |||
| Doxorubicin hydrochloride | 75 mg/m2/day infusion for 10 min | High risk | The incidence of symptomatic chronic heart failure is estimated to be 3%–4% after a cumulative dose of 450 mg/m2 if doxorubicin is administered as a bolus or short infusion of 45–75 mg/m2 every 3–4 weeks. | Biganzoli et al., 2003; Injac and Strukelj, 2008; Lee et al., 2010; Oakervee et al., 2005; Rahman et al., 2007 |
| 4.5 mg/m2/day continuous infusion for 4 days, repeated every 3 weeks | ||||
| Butylated hydroxytoluene (BHT) | Dermal 0.5% in body lotion | Low risk | Used safely in cosmetic products and foods. Existent consumer risk assessment from the SCCS. | SCCS, 2021b |
| Oxybenzone | Dermal 2% in a sunscreen | Low risk | Used safely as a UV filter in cosmetic products. Existent consumer risk assessment from the SCCS. |
SCCS, 2021a
Regulation (EC) No 1223/2009 |
| 0.5% in a body lotion | Low risk | |||
| 4-Hexylresorcinol | Oral throat lozenge (2.4 mg) | Low risk | Used safely as a throat lozenge. Antimicrobial and anesthetic effects are local only, supported by clinical data. | Matthews et al., 2020; McNally et al., 2012 |
| Dermal 0.5% face serum | Low risk | Used safely in cosmetic products. Exposure level supported by existent toxicological data. | EFSA Panel, 2014; Won et al., 2014 | |
| Oral food residue 3.3 µg/kg bw/day | Low risk | Existent consumer risk assessment from EFSA. | EFSA Panel, 2014 | |
| Caffeine | Oral dietary intake—400 mg/day | Low risk | No evidence for concern with respect to systemic toxicity from the available toxicological data, as concluded by EFSA, Health Canada, and the FDA. | Blanchard and Sawers, 1983; EFSA Panel on Dietetic Products, Nutrition and Allergies, 2015; Nawrot et al., 2003 |
| Dermal 0.2% shampoo | Low risk | |||
| Oral tablets/overdose >10 g | High risk | Evidence of serious adverse systemic effects, which can result in death. | Jabbar and Hanly, 2013 | |
| Dermal clinical (2 mg/cm2 of a solution containing 2.5% caffeine applied to a test area of 25 cm2) | Low risk | No evidence for concern with respect to systemic toxicity from the available toxicological data at this level, as concluded by EFSA, Health Canada, and the FDA. No reports of systemic effects from volunteers administered 1.25 mg topical caffeine as part of this clinical study. | Otberg et al., 2008 | |
| Coumarin | Oral dietary intake 4.085 mg/day | Low risk | Used safely in flavorings and other food ingredients with flavoring properties. Existent consumer risk assessment from EFSA. | EFSA, 2008 |
| Oral dietary intake 0.1 mg/kg bw/day | Low risk | |||
| Dermal 0.38% as a fragrance in body lotion | Low risk | Used safely as a fragrance in cosmetic products. Maximum level supported by RIFM fragrance ingredient safety assessment in this product type. | Api et al., 2020 | |
| Niacinamide | Tolerable daily intake (TDI) 12.5 mg/bw/day | Low risk | Used safely as a cosmetic ingredient and vitamin supplement. No evidence for concern with respect to systemic toxicity from the available toxicological data, as concluded by the Scientific Committee on Food and Scientific Panel on Dietetic Products, Nutrition and Allergies. Niacinamide is a form of vitamin B3 with a recommended intake of 10–15 mg/day of niacin equivalent. | Cosmetic Ingredient Review Expert Panel, 2005; EFSA NDA Panel, 2014; EFSA Panel on Nutrition, Novel Foods and Food Allergens, 2022 |
| Norwegian dietary intake 22.2 mg/day | Low risk | |||
| 0.1% in a hair conditioner | Low risk | |||
| 3% in a body lotion | Low risk | |||
| Sulforaphane | Dietary intake 3.9 mg/day | Low risk | Long history of sulforaphane consumption in cruciferous vegetables. However, there is an uncertainty in the sulforaphane human exposure due to the variation of sulforaphane content across the different vegetables and its formation from glucoraphanin depending on how vegetables are prepared. The exposure selected, for which concentration in humans were available, was considered representative of a high consumption of broccoli in the U.K. population (18.5 g/day) and assumed a high concentration of sulforaphane in broccoli (37–75 mg per 100 g of fresh weight). | Hanlon et al., 2009; Howard et al., 1997 |
| Oral 20 mg 3× daily | Low risk | No evidence of systemic effects in patients given this regimen as part of a clinical trial. | Cipolla et al., 2015 |