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EC number: 258-904-8
CAS number: 53988-10-6
Table 6.1.8/3: Nominal and mean measured concentrations
Test itemNominal conc.(mg/L)
Mean measured concentration (mg/L) at day
Relative to target [%]
1 Coefficient of variation; + Analyzed concentration is below limit of quantification (LOQ) of 0.0045 mg/L.
Table 6.1.8/4: Summary of effect parameters measured
Test item, Nominal conc. (mg/L)
Wet Weight 1
Snout-Vent Length (SVL) 2
Hind Limb Length (normalized by SVL)
Behaviour / Appearance
Wet Weight (NF stage ≤60)
Wet Weight (NF stage >60)
Snout-Vent Length (SVL) (NF stage ≤60)
Snout-Vent Length (SVL) (NF stage >60)
Thyroid Gland Histopathology
- Endpoint not impacted compared to the control (qualitative assessment)
↓ Endpoint significantly reduced
↑ Endpoint significantly increased
n.d. – Not determined. No suitable tadpoles available for assessment.
o Identified NOEC
1 EC10: 4.4 mg/L, EC20: 8.7 mg/L
2 EC10: 10 mg/L
This Amphibian Metamorphosis Assay (AMA) was performed to identify whether the test item may interfere with the normal function of the hypothalamic-pituitary-thyroid (HPT) axis, according to OECD Test Guideline 231 with GLP statement. The AMA represents a generalized vertebrate model to the extent that it is based on the conserved structures and functions of the HPT axis. The African clawed frog (Xenopus laevis) was used for this purpose.
According to a 14-days toxicity test, Xenopus laevis tadpoles were exposed to the test item at analytically confirmed nominal concentrations of 0.0048, 0.024, 0.12, 0.60, 3.0 and 15 mg/L and to a control, over a period of 21 days under flow-through conditions. Four replicates were used, each containing 20 tadpoles of Developmental (NF) stage 51 at the start of the test, except for one replicate of the control which had received 19 tadpoles of NF stage 51 and two replicates in the highest test concentration which had received, both, 21 tadpoles of NF stage 51.
The study met the acceptability criteria and was considered valid.
On Day 7 of exposure, effects observed at the two highest test concentrations suggest a slight delay to development coupled with overt signs of toxicity. As elaborated in the OECD TG 231, mild developmental delays coupled with overt signs of toxicity likely indicate a non-specific toxic effect. Similarly, mild reductions in growth, as determined by Wet Weight (WW) and/or Snout-to-Vent Length (SVL), also suggest non-thyroidal toxicity. Considering that no clear retardation was observed in the developmental parameters, the recorded findings on WW and SVL at Day 7 likely suggest systemic toxic effects rather than anti-thyroidal effects.
On Day 21 of exposure, several observations were made at the highest two test concentrations that were related to retardation of development. Firstly, the group median developmental stages were slightly to significantly lower than in the control; the difference of developmental stages was statistically significant at the highest concentration. Additionally, Hind Limb Length (HLL) normalized for SVL at the two highest test concentrations was significantly lower than in the control, suggesting a decreasing trend in the normalized HLL as concentration increased.
These two endpoints are associated with metamorphosis and as such, are sensitive to changes in the functioning of the HPT axis. As mentioned above, delayed development can occur through two ways - anti-thyroidal mechanisms or indirect toxicity. Mild developmental delays coupled with overt signs of toxicity likely indicate a non-specific toxic effect.
In the present study, no excessive mortality was observed but other signs of systemic toxicity were observed, i.e. SVL and wet body weight were clearly affected by test item exposure. On the other hand, developmental delays at the end of exposure could not be considered mild as there was no overlap of developmental stages in the highest test concentration and the control group. Also, the histopathological assessment of the thyroid glands indicated clear tissue alterations related to test item exposure.
It should be noted that the developmental delay at the higher concentrations conflicted with the possibility of selecting tadpoles matched to the median developmental stage in the control group. Following Grim et al. (2009), the differences in thyroid gland histopathology between NF stages 57 and 62 are not strong enough to conflict with the conclusions drawn by the histopathological assessment in the present study for the different treatment levels. Based on the observed thyroid histopathology, the test item clearly affected the thyroid gland of exposed tadpoles. The lowest 21d-NOEC value was determined at 0.024 mg/L.
To conclude, neither advanced, nor asynchronous development were observed in the present study. However, remarkable histological effects were noted at concentrations of 0.12 mg/L and higher, including assignment of ‘severe degree’ grading for the core assessed criteria at 3.0 mg/L and 15 mg/L. Consequently, following the decision logic presented in OECD TG 231, the test item is concluded to be thyroid active. As no mortality occurred in the control group, the study is considered valid.
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