Table 12.
Repeated dose toxicity studies on SCCPs in rats and mice
| Species/ strain | Number of animals per group | SCCP specification | Duration | Administration | Dose levels (mg/kg bw per day) | Most sensitive endpoints | NOAEL (mg/kg bw per day) | LOAEL (mg/kg bw per day) | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Studies in rats | |||||||||
| F344 rat | 5/sex per group |
C10–12, 58% chlorination |
14 days | Diet | 0, 100, 300, 1,000, 3,000 | ↑ absolute and relative liver weights, ↑ incidence of hepatocellular hypertrophy | – | 100 | IRDC (1983a)a |
| F344 rat | 5/sex per group |
C10–12, 58% chlorination |
14 days | Gavage (corn oil) | 0, 30, 100, 300, 1,000, 3,000 | ↑ relative liver weights in males | 30 | 100 | IRDC (1981a)a |
| Alpk:APfSD rat | 5/males per group |
Cereclor 56L, C10–13, 56% chlorination |
14 days | Gavage (corn oil) | 0, 10, 50, 100, 250, 500, 1,000 | ↑ relative liver weightsb | 10 | 50 | Wyatt et al. (1993) |
| Alpk:APfSD rat | 5/males per group | Chlorowax 500C, C10–13, 58% chlorination | 14 days | Gavage (corn oil) | 0, 10, 50, 100, 250, 500, 1,000 | ↑ absolute and relative liver weights | 50 | 100 | Wyatt et al. (1993) |
| F344 rat | 5/sex per group |
C12, 60% chlorination |
16 days | Gavage (corn oil) | 0, 469, 938, 1,875, 3,750, 7,500 | Liver enlargement | – | 469 | NTP (1986a), Bucher et al. (1987) |
| Sprague–Dawley rat | 9/males per group |
C10–13, 56.5% chlorination |
28 days | Gavage (corn oil) | 0, 1, 10, 100 | ↓ plasma FT3, ↑ plasma TSH | 1 (NOEL) | 10 (LOEL) | Gong et al. (2018) |
| F344 rat |
15/sex per group |
C10–12, 58% chlorination |
90 days | Diet | 0, 10, 100, 625 | ↑ absolute and relative liver and kidney weights; histopathological changes such as hepatocellular hypertrophy (both sexes), mild nephritis (males only), and thyroid hypertrophy and hyperplasia (males only) | 10 | 100 | IRDC (1984a)a, Serrone et al. (1987) |
| F344 rat | 15/sex per group |
C10–12, 58% chlorination |
90 days |
Gavage (corn oil) |
0, 10, 100, 625 | ↑ absolute and relative liver and kidney weights; histopathological changes such as hepatocellular hypertrophy (males only), mild nephropathy (males only) | 10 | 100 | IRDC (1984b)a, Serrone et al. (1987) |
| F344 rat | 10/sex per group |
C12, 60% chlorination |
90 days | Gavage (corn oil) | 0, 313, 625, 1,250, 2,500, 5,000 | ↑ relative liver weights | – | 313 | NTP (1986a), Bucher et al. (1987) |
| F344 rat |
50/sex per group 20/sex per group |
C12, 60% chlorination |
2 years | Gavage (corn oil) | 0, 312, 625 | ↑ liver and kidney weights; histopathological finding in the liver, kidney, stomach, forestomach and parathyroid | – | 312 | NTP (1986a), Bucher et al. (1987) |
| Studies in mice | |||||||||
| Alpk:APfCD‐1 mouse | 5/males per group | Cereclor 56L, C10–13, 56% chlorination | 14 days | Gavage (corn oil) | 0, 10, 50, 100, 250, 500, 1,000 | ↑ absolute and relative liver weights | 50 | 100 | Wyatt et al. (1993) |
| Alpk:APfCD‐1 mouse | 5/males per group | Chlorowax 500C, C10–13, 58% chlorination | 14 days | Gavage (corn oil) | 0, 10, 50, 100, 250, 500, 1,000 | ↑ relative liver weights | 100 | 250 | Wyatt et al. (1993) |
| B6F3C1 mouse | 5/sex per group |
C12, 60% chlorination |
16 days | Gavage (corn oil) | 0, 938, 1,875, 3,750, 7,500, 15,000 | liver enlargement | – | 938 | NTP (1986a), Bucher et al. (1987) |
| B6F3C1 mouse | 10/sex per group |
C12, 60% chlorination |
90 days | Gavage (corn oil) | 0, 125, 250, 500, 1,000, 2,000 | ↑ relative liver weights (females), hepatocellular hypertrophy (both sexes) | 125 | 250 | NTP (1986a), Bucher et al. (1987) |
| B6F3C1 mouse | 50/sex per group |
C12, 60% chlorination |
2 years | Gavage (corn oil) | 0, 125, 250 | Histopathological findings in the kidney (females only) and in the thyroid (both sexes) | – | 125 | NTP (1986a), Bucher et al. (1987) |
SCCPs: short‐chain chlorinated paraffins; NOAEL: no‐observed adverse effect level; LOAEL: lowest‐observed adverse effect level; bw: body weight; T3: triiodothyronine; TSH: thyroid‐stimulating hormone; FT3: free T3.
Unpublished study report, see Documentation provided to EFSA.
For absolute liver weight increase, the lowest significant effect was at 10 mg/kg bw per day but followed an irregular dose response. As consequence, it was not used for the determination of NOAEL and LOAEL.