Table 2.
TRVs identified in the literature for the general population and breakdown of how each value was derived
| Reference | TRV | Value (mg kg–1 day–1) | Exposure duration, route | Critical effect | Key study | Point of departure | Composite adjustment factor (individual adjustments) |
|---|---|---|---|---|---|---|---|
| ECHA (2017) | DNEL | 2.5 | Chronic, oral | Unidentified; however, the registration dossier states “a chronic study is used to set a chronic DNEL. No correction required” | Mice, oral gavage (study citation not clear) | NOAEL = 250 mg kg–1 day–1 | 100 (UFA = 10, UFH = 10) |
| Colnot et al. (2014) | DNEL | 5 | Chronic, oral | No reproductive/developmental effects | Rats, oral gavage (MPI Research, 2002b, cited in Colnot et al., 2014) | NOAEL = 1000 mg kg–1 day–1 | 200 (UFA = 10, UFH = 10, UFS = 2) |
| Colnot et al. (2014) | DNEL | 0.16 | Chronic, oral | Thyroid hormone changes | Rats, dietary (Van der Ven et al., 2008, cited in Health Canada, 2013 and EFSA, 2011) | BMDL10 = 16 mg kg–1 day–1 | 100 (UFA = 10, UFH = 10) |
| Colnot et al. (2014) | DNEL | 10 | Chronic, oral | No reproductive/fertility effects | Rats, oral gavage (MPI Research, 2001, cited in Colnot et al., 2014) | NOAEL = 1000 mg kg–1 day–1 | 100 (UFA = 10, UFH = 10) |
| COT (2004) | TDI | 1 | Chronic, oral | No embryotoxic/teratogenic effects | Rats, oral gavage (MPI, 2002b, cited in Colnot et al., 2014) | NOAEL of 1000 mg kg–1 day–1 | 1000 (UFA = 10, UFH = 10, UFD = 10) |
| Wikoff et al. (2015) | RfD | 0.6 | Chronic, oral | Uterine endometrial atypical hyperplasia | Rats, oral gavage (NTP, 2014) |
BMDL10 = 72.8 mg kg–1 day–1
HED = 18.2 mg kg–1 day–1 |
30 (UFA = 3; UFH = 10) NSRL for cancer precursor effect for 70 kg human = 42 mg kg–1 day–1 |
| Pecquet et al. (2017, this paper) | RfDcancer | 0.3 | Chronic, oral | Uterine tumors | Rats, oral gavage (NTP, 2014) |
BMDL10 = 102.5 mg kg–1 day–1
HED = 25.6 mg kg–1 day–1 |
100 (UFA = 3; UFH = 10; UFD = 3) NSRL for 70 kg human = 20 mg kg–1 day–1 |
| Wikoff et al. (2015) | Cancer slope factor | 0.00315 | Chronic, oral | Uterine tumors | Rats, oral gavage (NTP, 2014) |
BMDL10 = 126.6 mg kg–1 day–1
HED = 31.7 mg kg–1 day–1 |
RSD at 10–6 = 0.0032 mg kg–1 day–1
NSRL for 70 kg human = 0.22 mg kg–1 day–1 |
BMDL10, benchmark dose lower limit; DNEL, derived no effect level; HED, human equivalent dose; NOAEL, no‐observed‐adverse‐effect‐level; NSRL, no‐significant‐risk‐level; RSD, risk‐specific dose; TDI, tolerable daily intake; TRV, toxicity reference value.