Table 2.
Dose–response modeling for potential human carcinogens occurring in alcoholic beverages (reprinted with permission from Springer Nature, Archives of Toxicology, Pflaum et al. [1] copyright 2016).
| Carcinogenic Agent | Modeling Toxicological Endpoint | Animal Model | Route/Mode of Exposure | BMDL a | |
|---|---|---|---|---|---|
| (mg/kg bw/Day) | Reference | ||||
| Acetaldehyde | Animal tumors [60] | Male rats | Oral | 56 | [60] |
| Acrylamide | Harderian gland tumors [63] | Mice | Oral | 0.18 | [64] |
| Aflatoxin B1 | Cancer of the lungs in humans [65] | NA | Food | 0.00087 | [66] |
| Arsenic | Cancer of the lungs in humans [67] | NA | Water | BMDL0.5: 0.003 | [68] |
| Benzene | Human lymphocyte count [69] | NA | Inhalation extrapolated to oral | 1.2 b | [70] |
| Cadmium | Human studies [70] | NA | Food | NOAEL: 0.01 c | [70] |
| Ethanol | Hepatocellular adenoma or carcinoma [71] | Rats | Oral | 700 | [72,73] |
| Ethyl carbamate | Bronchiolar alveolar carcinoma [74] | Mice | Oral | 0.3 | [73] |
| Formaldehyde | The aerodigestive tract, comprising the oral and gastrointestinal mucosa, undergoes histological alterations [75] | Rats | Oral | NOEL: 15 c | [76] |
| Furan | Adenomas and carcinomas of the liver [77] | Female mice | Oral | 0.96 | [78] |
| Glyphosate b | There are no dose–response data for the cancer outcome | NOAEL: 50 | [79] | ||
| Lead | Human cardiovascular effects [29] | NA | Diet | BMDL10: 0015 d | [80] |
| 3-MCPD | Hyperplasia of the tubules of the kidneys e [81] | Rats | Oral | 0.27 | [82] |
| 4-Methylimidazole | Lung cancer [83] |
Mice | Oral | NOAEL: 80 c | [84] |
| N-Nitrosodimethylamine | Hepatocellular carcinoma [85] | Oral | 0.029 | [86,87] | |
| Ochratoxin A | Renal adeno-carcinoma [88] | Male rats | Oral | 0.025 | [89] |
| Pulegone | Urinary bladder tumors [90] | Rats | Oral | LOAEL: 20 c | [49] |
| Safrole | Hepatic tumors [91] | Mice | Oral | 3 f | [92,93] |
NA—not applicable. a For an x % occurrence of health effect, BMDLx is the lower one-sided confidence limit of the benchmark dose (BMD). b Inhalation exposure was used as the original endpoint. Route-to-route extrapolation was used to calculate the BMDL for oral exposure [69]. c The no effect level (NOEL), no observed adverse effect level (NOAEL), or lowest observed adverse effect level (LOAEL) were utilized because no appropriate BMD modeling for exposure through the mouth has been documented. d Overall exposure to lead is determined in blood, and the figures are based on that. The BMDL that was employed was determined based on dietary exposure [29]. e Renal tubular hyperplasia, rather than renal tubule adenoma or cancer, was a more sensitive endpoint. f This was a conservative minimal concentration based on the literature’s BMDL10 range of “about 3–29 mg/kg bw/day” for safrole [91].