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 = 0.0015 μg/L

Where:

A = 11 kg (total sold amount API in Sweden year 2022, data from IQVIA) (Ref. I)

R = 0 % removal rate (worst case assumption)

P = number of inhabitants in Sweden = 10 *10⁶

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

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Pseudokirchneriella subcapitata) (OECD 201) (Ref. III):

EC₅₀ 72 h (growth rate) > 90 mg/L

NOEC = 40 mg/L

Crustacean, water flea (Daphnia magna):

Acute toxicity

EC₅₀ 48 h (growth rate and biomass) > 100 mg/L (OECD 202) (Ref. IV)

NOEC = 100 mg/L

No effects seen up to highest concentration tested

Fish, rainbow trout (Oncorhynchus mykiss):

Acute toxicity

LC₅₀ 96 h (mortality) > 100 mg/L (OECD 203) (Ref.V)

NOEC = 100 mg/L

No effects seen up to highest concentration tested

PNEC =90 μg/L (90,000 μg/L/1000 based on the most sensitive acute EC₅₀ for the green algae with an assessment factor (AF) of 1000)

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0015/90 = 0.000017, i.e. PEC/PNEC ≤ .1 which justifies the phrase "Use of temozolomide has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

Test results: 61% elimination (loss of parent) at Day 21, 83% to CO₂ at Day 35 (OECD 301B) (Ref. VI)

Abiotic degradation

Hydrolysis:

Half-life = 69 days at pH 4 and < 1 day at pH 7 and pH 9 (OECD 111) (Ref. VII)

Justification of chosen degradation phrase:

83% of temozolomide degrades to the nonhazardous CO₂ within 35 days. Therefore, significant mineralization is expected and thus the phrase “Temozolomide is slowly degraded in the environment” is chosen.

Bioaccumulation

Partitioning coefficient:

Log K_ow = 1.35 at pH 7

• The partition coefficient (K_ow) was determined for the equilibrium distribution of temozolomide between n-octanol and 0.1N HCl, and n-octanol and pH 7 phosphate buffer. Equal volumes of the aqueous component, containing about 1 mg/mL temozolomide, and n-octanol were agitated for 6 hours at ambient temperature. After centrifugation, both layers were assayed for temozolomide content by HPLC (Ref VIII).

Justification of chosen bioaccumulation phrase:

Since log K_ow < 4 at pH 7, the substance has low potential for bioaccumulation.

References

1. Data from IQVIA ”Consumption assessment in kg for input to environmental classification - updated 2023 (data 2022)”.

2. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm

3. Huntington Life Sciences, 2006. "SCH 52365 Algal Growth Inhibition Assay," Study No. ESN 213/052201, HLS, England, 22 February 2006.

4. Huntington Life Sciences, 2006. "SCH 52365 Acute Toxicity to Daphnia magna," Study No. ESN 212/052200, HLS, England, 22 February 2006.

5. Huntington Life Sciences, 2006. "SCH 52365 Acute Toxicity to Rainbow Trout," Study No. ESN 211/052199, HLS, England, 22 February 2006.

6. Huntington Life Sciences, 2005. "SCH 52365 Assessment of Ready Biodegradability: Modified Sturm Test," Study No. ESN 209/043479, HLS, England, 19 April 2005.

7. Huntington Life Sciences, 2005. "SCH 52365 Abiotic Degradation: Hydrolysis as a Function of pH," Study No. ESN 208/043624, HLS, England, 20 July 2005.

8. Schering Plough Research Institute. CMC Section 4.A.1.2 Temozolomide (SCH 52365) Capsules - Physical Chemical Characterization.