Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

PEC is calculated according to the following formula:

PEC (μg/L) = (A*10⁹*(100-R))/(365*P*V*D*100) = 1.37*10^-6*A(100-R)

PEC = 0.66 μg/L

Where:

A = 4792.4433 kg (total sold amount API in Sweden year 2021, data from IQVIA).

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)

P = number of inhabitants in Sweden = 10*10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref I)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Selenastrum capricornutum):

Sevelamer carbonate: ELr₅₀ 72 h (loading rate) = 63 000 µg/L,

NOELr 72 h (loading rate)= 18 000 µg/L

(method^†) (Ref II, III)

Algae (Pseudokirchneriella subcapitata):

Sevelamer hydrochloride: ELr₅₀ 72 h (loading rate)= 25 000 µg/L,

NOELr 72 h (loading rate)= 6 000 µg/L

(method^†) (Ref III)

Crustacean (Daphnia magna):

Sevelamer carbonate: ELr₅₀ 48 h (loading rate) > 1*10⁶ µg/L,

NOELr 48 h (loading rate) = 450 000 µg/L

(method^†) (Ref IV)

Sevelamer hydrochloride: ELr₅₀ 48 h (loading rate) > 1*10⁶ µg/L,

NOELr 48 h (loading rate) = 62 500 µg/L

(method^†) (Ref V)

Fish (Oncorhynchus mykiss):

Sevelamer carbonate: Read across
Sevelamer hydrochloride: LLr₅₀ 96 h (loading rate) = 82 000 µg/L,

NOELr 96 h (loading rate) = 15 600 µg/L

(method^†) (Ref VI)

^†Method used: Endpoints are expressed as loading rates (e.g. median lethal loading rate, LLr₅₀, analogous to conventional LC₅₀ estimates), due to the insolubility of sevelamer carbonate in water. The studies conducted for sevelamer hydrochloride used test solutions that were prepared by direct addition to the test water, after which the test organisms were added. The tests with sevelamer carbonate were conducted as with sevelamer hydrochloride, with the exception that solutions were filtered (0.45 μm) prior to exposure of the test organisms, so that only the soluble/leachable polymer was assessed. The method used with sevelamer hydrochloride was an acceptable method at the time of testing, however subsequent OECD guidance (Ref VII), suggests that non-dissolved material should be removed from test vessels prior to addition of the test organism, so that physical effects such as smothering and irritation are not misinterpreted as direct toxicity mechanisms attributed to the test material.

Environmental risk classification (PEC/PNEC ratio)

Because ecotoxicological test results were based on loading rates and not on the concentration in the test medium that the organisms were exposed to the PNEC could not be calculated. However, the environmental risk phrase should be: "Risk of environmental impact of sevelamer cannot be excluded, since there is not sufficient ecotoxicity data available".

Degradation

No direct or indirect abiotic or biotic degradation pathways for sevelamer have been identified. The futher fate in the environment, with regards to the chelation sites of sevelamer, is not known. It is likely that sevelamer will biodegrade at least slowly over time via the formation to simple carbon and nitrogen molecules (based on the monomer). However, there still exists the possibility that sevelamer carbonate could accumulate, particularly in agricultural land. It is quite possible that as a result of soil microbial adaptation to sevelamer carbonate, accumulation will be reduced to levels well below the safe value. (Ref VIII). However, since no data are available the summary phrase for degradation should be: "The potential for persistence of sevelamer cannot be excluded, due to lack of data".

Bioaccumulation

Sevelamer carbonate is a member of a group of highly cross-linked polymers that are insoluble in either water or organic solvents, therefore a meaningful Log K_ow cannot be estimated (Ref VIII). However, since no data are available the summary phrase should be: "The potential for bioaccumulation of sevelamer cannot be excluded, due to lack of data".

Excretion (metabolism)

Sevelamer hydrochloride is not systemically absorbed. As this will also be the case with sevelamer carbonate, 100% of the ingested dose will be excreted in the faeces, in the form of an insoluble gel. The chelation sites of the polymer will be “filled” either by the passage through the patient or in the ion rich environment of sewage treatment plants, and will essentially be in an inactive form when discharged into the environment. (Ref VIII)

References

1. ECHA, European Chemicals Agency, 2008 Guidance on information requirements and chemical safety assessment. https://echa.europa.eu/sv/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment

2. KirK H. D., Miller J. A.., and McFadden L. G. (1997) Evaluation of Acute Toxicity of Sevelamer Hydrochloride to Selenastrum capricornutum. Dow Chemical Company Study Report 971049

3. Charles River Laboratories Study No. 807236, Report No. 27541. Sevelamer Carbonate: Alga, Growth Inhibition Test, 2007

4. Charles River Laboratories Study No. 807220, Report No. 27542. Sevelamer Carbonate: Determination of Acute Toxicity to Daphnia (48 h, Static), 2007

5. Weinberg J. T. and Miller J. A. (1997) Evaluation of Acute Toxicity of Sevelamer Hydrochloride to Daphnia magna STRAUS. Dow Chemical Company Study Report 48674

6. Weinberg J. T. and Miller J. A. (1997) Evaluation of Acute Toxicity of Sevelamer Hydrochloride to Rainbow Trout Oncorhynchus mykiss Walbaum. Dow Chemical Company Study Report 971048

7. Guidance Document on Aquatic Toxicity Testing of Difficult Substances and Mixtures, 2006

8. Confidential Environmental Risk Assessment of Sevelamer Carbonate/Renvela, Genzyme, Mar 2008