Table 13
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Skip the menu of subheadings on this page.This is a paper for discussion. This does not represent the views of the Committee and should not be cited.
Table 13. Repeated dose toxicity studies for PFCAs - PFDoDA
*Derived by contractor; ** calculated according to EFSA. (2012); NR – not reported; NA – not applicable.
|
Substance / CAS no. / purity / reference |
Strain & species / sex / no. of animals |
Dose (mg/kg bw/day) / vehicle / route of admin / duration / Guideline (GL) study / Good Laboratory Practice (GLP) status |
PFAS concentration (µg/mL / µg/g) |
Observed effects at LOAEL (controls vs treated groups). Recovery (controls vs treated groups). |
Published NOAEL / LOAEL (mg/kg bw/day) |
Study author comments |
Comments |
|
PFDoDA CAS No. not given 97%. Kato et al. (2014) |
Crl:CD (SD) rats. Male and female. 12/sex/dose. Recovery: 5 males and females. |
0, 0.1, 0.5 or 2.5. Corn oil, Gavage, 42 days (males), 41-46 days (females), OECD 422, GLP not stated. Recovery: 0 or 1, 14 days. |
NR |
Males (mean ± SD): ↑ relative liver weight (%): 2.51 ± 0.14 vs 3.00 ± 0.30#. ↑ ALP (IU/L): 357.2 ± 28.6 vs 551.6 ± 95.2#. ↓ total cholesterol (mg/dL): 67.0 ± 9.7 vs 40.6 ± 7.8#. Females: ↑ albumin/globulin ratio: 0.92 vs 0.09 vs 1.13 ± 0.08#. ↑ relative liver weight (%): 3.23 ± 0.19 vs 3.70 ± 0.22#. ↑ focal necrosis: 0 vs 2 (grade 2). Recovery: Data not presented as animals only treated with 200 mg/kg bw/day and not 0.5 mg/kg bw/day (LOAEL). |
Males: 0.1 / 0.5.
Females: 0.1 / 0.5.
|
Data suggested that the liver is a sensitive target organ as various histopathological changes, including hepatocyte hypertrophy and necrosis, were observed in the liver in both sexes. The NOAEL for repeated dose toxicity is 0.1 mg/kg bw/day based on centrilobular hypertrophy of hepatocytes in both sexes at 0.5 mg/kg bw/day. |
K1 The study investigated the toxicity of PFUnDA in rats. The study was carried out according to OECD 422. #measured in 5 animals/dose. Study was funded under the Japanese safety programme for existing chemicals, funded by the Ministry of Health, Labour and Welfare, Japan. |
|
PFDoDA CAS No. 307-55-1 99%. Zhang et al. (2008) |
Sprague-Dawley rats. Male, 10/dose. |
0, 1, 5 or 10. Gavage, 14 days, Tween 20, Non-GL stud,y GLP not stated. |
NR |
Males (mean ± SEM): ↑ hepatic SOD activity: data only presented in figures. ↑ mRNA of PPAR-α/g, Acox and CypA4: data only presented in figures. Recovery not assessed. |
Males: NA / 1* |
Rats exposed to low doses of PFDoA exhibited the trend to decrease serum TG and cholesterol, similar to those seen in other PFCAs. |
K2 This study investigated if PFDoA exposure has similar effects in the male rat liver as other PFCAs that have shorter carbon lengths, focussing on lipid homeostasis and oxidative stress. Only male animals were used. Limited endpoints were measured. Liver weight, TG and cholesterol were only increased at higher doses. Although authors concluded that TG and cholesterol were decreased at low doses, such decreases were only seen at the highest dose and not at the LOAEL. Funded by the National Natural Science Foundations of China and the Innovation Program of the Chinese Academy of Sciences. |