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EC number: 441-420-8 | CAS number: 113889-23-9
Bioaccumulation: terrestrial
Administrative data
Link to relevant study record(s)
Description of key information
The BCF in earthworms was estimated with the equation from Jager (1998) which is incorporated in the EUSES model and is applicable to substances with a log Kow value ranging from 1-8: BCFworm = (Fwaterworm + Flipidworm*Kow)/RHO worm where Fwaterworm = 0.84, Flipidworm = 0.012 and RHO worm = 1 kg ww/l. Entering the log Kow value of 4.48 for the substance results in a BCFearthworm of 363 l/kg ww (earthworm).
The metabolisation of Cyclobutanate, being an ester will be fast due to carboxylesterases present in all (vertebrate) organisms (Wheelock et al., 2008). The de-esterification and the formation of Cycla-alcohol is experimentally detected in the MITI test (OECD TG 301C. After 28 days no Cyclobutanate was found only Cycla-alcohol showing that the ester was fully cleaved. Butanoic acid was searched for but not found and was likely consumed by the bacteria as feed.
Using the QSAR model BCFBAF, the DT50 is estimated to be 0.34 days (DT50 < 1 day). The transformation product Cycla-alcohol as such has a log Kow around 2 (2.4 measured and 1.8 calculated). This alcohol is a secondary alcohol and will be conjugated in Phase II metabolic systems with Glucuronic acid, which has a low log Kow of << 2 (Glucuronic acid has a log Kow of -1.87 as presented in PubChem). This glucuronidation has been derived from an EFSA publication on secondary alcohols using similar substances as Cyclobutanate (e.g. EFSA, 2012, see Toxicokinetic section for reference). Based on these profiles the DT50 is estimated to be < 1 day. Beside the short DT50, the kidney is the key excretion pathway. This is based on the toxicity effect seen in male rat: alpha-hydrocarbon nephropathy after repeated exposure. This means that urine is the key excretion route. The other metabolite is butyric acid, which is a normal constituent of the body and can be consumed in the Krebs cycle. In view of the metabolic profile of Cyclobutanate there is no concern for this substance or its metabolites for biomagnification in air breathing organisms, see also Toxico-kinetic section.
Key value for chemical safety assessment
- BCF (terrestrial species):
- 363 L/kg ww
Additional information
Cyclobutanate does not bioaccumulate in air breathing organisms, despite fulfilling the screening criteria on log Kow (> 2) and log Koa (> 5). Bioaccumulation in air breathing organisms is not relevant for metabolizing substances as Gobas et al.explicitly mentions (2020, figure 6, D, assessing oxygen containing substances). The metabolisation of Cyclobutanate, being an ester will be fast due to carboxyl esterases present in all (vertebrate) organisms (Wheelock et al., 2008). Using the QSAR model BCFBAF, the DT50 is estimated to be 0.34 days (DT50 < 1 day). The transformation product Cycla-alcohol as such has a log Kow around 2 (2.4 measured and 1.8 calculated). This alcohol is a secondary alcohol those will be conjugated in mammals with Glucuronic acid, which has a low log Kow of << 2 (Glucuronic acid has a log Kow of -1.87 as presented in PubChem). This glucuronidation has been derived from an EFSA publication on secondary alcohols using similar substances as Cyclobutanate (e.g. EFSA, 2012, see Toxicokinetic section for reference). Based on these profiles the DT50 is estimated to be < 1 day. Beside the short DT50, the kidney is the key excretion pathway. This is based on the toxicity effect seen in male rat: alpha-hydrocarbon nephropathy after repeated exposure. This means that urine is the key excretion route. The other metabolite is butyric acid, which is a normal constituent of the body and can be consumed in the Krebs cycle. In view of the metabolic profile of Cyclobutanate there is no concern for this substance or its metabolites for biomagnification in air breathing organisms, see also Toxico-kinetic section.
The formation of Cycla-alcohol is experimentally detected in the MITI test (OECD TG 301C. After 28 days no Cyclobutanate was found only Cycla-alcohol showing that the ester was fully cleaved. Butanoic acid was searched for but not found and was likely consumed by the bacteria as feed.
References
Gobas, F.A.P.C., Lee, Y-S, Lo, J.C., Parkerton, T.F., Letinskid, D.J., 2020, A Toxicokinetic Framework and Analysis Tool for Interpreting Organisation for Economic Cooperation and Development Guideline 305 dietary bioaccumulation test, Environ. Toxicol. Chem., 39, 171-188.
Wheelock, C.E., Philips, B.M., Anderson, B.S., Miller, J.L., Miller, M.J., and Hammock, B.D., 2008, Application of carboxylesterase activity in environmental monitoring and toxicity identification evaluations, (TIEs), in Reviews of Environmental Contamination an Toxicology, ed. Whitacre, 117-178, D.M., Springer.
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