2,5,7,10,11,14-hexaoxa-1,6-distibabicyclo[4.4.4]tetradecane

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity, other

Remarks:

intraperitoneal injection

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Data source

Reference

Reference Type:

publication

Title:

Antimony-induced neurobehavioural and biochemical perturbations in mice

Author:

Tanu, T. et al.

Year:

2018

Bibliographic source:

Biological Trace Element Research; https://doi.org/10.1007/s12011-018-1290-5

Materials and methods

Principles of method if other than guideline:

Tanu, T. et al. (2018):
Test substance: Antimony potassium tartrate hydrate
Dose/concentration: 10 mg/kg bw
Control(s): vehicle control (physiological saline)
No. of animals per sex per dose: 6 male mice
Duration of treatment / exposure: 8 weeks
Frequency of treatment: 3 times/week
Parameters investigated: anxiety-like behaviour (elevated plus maze), learning and memory impairment (Morris water maze), antimony concentration in brain tissue, biochemical analysis of serum (urea, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and butyryl cholinesterase) and histopathology of liver and kidney

Test material

Test material information

Constituent 1

Reference substance name:

28300-74-5

Cas Number:

28300-74-5

IUPAC Name:

28300-74-5

Test animals

Species:

other: Tanu, T. et al. (2018): mice (Swiss Albino)

Sex:

male

Administration / exposure

Route of administration:

other: Tanu, T. et al. (2018): intraperitoneal injection

Results and discussion

Effect levels

Remarks on result:

other: see "Remarks"

Remarks:

Tanu, T. et al. (2018): mice exposed to antimony potassium-tartrate hydrate (Sb) significantly (p < 0.05) decreased the time spent in open arms while increased the time spent in closed arms compared to the control mice in elevated plus maze. The mean latency time of control group to find the platform decreased (p < 0.05) significantly during 7 days learning as compared to Sb-treated group in Morris water maze test, and Sb-exposed group spent significantly (p < 0.05) less time in the desired quadrant as compared to the control group in probe trial. Furthermore, a significant Sb accumulation in the brain of Sb-exposed mice was found. In addition, Sb-exposure significantly increased alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase activities as well as serum urea and creatinine levels, while decreased butyryl cholinesterase activity compared to the control mice. Lastly, hepatic and renal dysfunction were observed.

Applicant's summary and conclusion

Conclusions:

Tanu, T. et al. (2018):
This is a non-GLP non-guideline study using a mouse of non-standard strain and supplier. The group size of 6, is inadequate for a definitive assessment of behavioural changes, which are notoriously difficult to assess, and there is no indication of adequate historical control data for either maze used to determine the magnitude of change required to confirm treatment effect. The sex of animals is not reported, yet can influence maze behaviour. The route of administration (IP), dose level and dosing regimen (3 doses per week for 8 weeks), is not compliant with OECD 424. No body weight or clinical observation data are provided, but histopathology and clinical chemistry data suggest a significant level of systemic toxicity which could also affect maze performance. There method for preparation of samples for Sb concentration in brain tissue and tissue samples for histopathology are non-standard. The reported levels in brain tissue are inconsistent with previous data which suggest that Sb accumulates primarily in the spleen, thyroid and liver (Coelho 2014).

Conclusion: The group size in this study is too small to provide a definitive assessment of behavioural changes (OECD 424 specifies a group size of 10M:10F). The data provided are insufficient to determine the level of systemic toxicity and whether any of the reported behavioural changes are secondary to any such general adverse effects. The study should be considered Klimisch 3 as the study is non-GLP, non-guideline and the documentation is insufficient to confirm the reported outcome.