Detaljerad miljöinformation

Detailed background information
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 = 0.36 μg/L

Where:

A = 2,619.65 kg (total sold amount API in Sweden year 2020, data from IQVIA). Reduction of A may be justified based on metabolism data.

R = 0% removal rate (conservatively, it has been assumed there is no 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. 1)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref. 1)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Scenedesmus subspicatus):

IC50 96h (growth) = 39,700 μg/L (OECD 201) (Reference 27)

NOEC = 7,500 μg/L

Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) = 56,000 μg/L (OECD 202) (Reference 38)

Water flea (Ceriodaphnia dubia):

Chronic toxicity

NOEC 8 days (reproduction) = 10,000 μg/L (USEPA 1002) (Reference 410)

Rainbow Trout (Oncorhyncus mykiss):

Acute toxicity

LC50 96 h (lethality) = 85,000 μg/L (OECD 203) (Reference 59)

Fish:

Chronic toxicity

No data

Other ecotoxicity data:

Microorganisms in activated sludge:

EC50 3 h (inhibition) = 1,000,000 μg/L @ 3 hrs (OECD 209) (Reference 65)

PNEC = 7,500/50 = 150 μg/L

PNEC (μg/L) = lowest NOEC/50, where 50 is the assessment factor applied for two long-term NOECs. NOEC for alga (= 7,500 µg/L) has been used for this calculation since it is the most sensitive of the three tested species

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.36/150= 0.0024, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of lamotrigine has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

Ready degradability:

<1% degradation in 28 days (TAD 3.11). (Reference 74)

Inherent degradability:

<10% degradation in 28 days (OECD 302). (Reference 86)

Abiotic degradation

Hydrolysis:

No data

Photolysis:

No data

Justification of chosen degradation phrase:

Lamotrigine is not readily degradable or inherently degradable. The phrase “Lamotrigine is potentially persistent” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Dow = 1.54 at pH 7.4 (TAD 3.02). (Reference 93)

Log Dow at pH 5 < 1

Log Dow at pH 7 = 1.4

Log Dow at pH 9 = 1.4

Justification of chosen bioaccumulation phrase:

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

Excretion (metabolism)

UDP-glucuronyl transferases have been identified as the enzymes responsible for metabolism of lamotrigine. Lamotrigine induces its own metabolism to a modest extent depending on dose. However, there is no evidence that lamotrigine affects the pharmacokinetics of other AEDs and data suggest that interactions between lamotrigine and medicinal products metabolised by cytochrome P450 enzymes are unlikely to occur.

The apparent plasma clearance in healthy subjects is approximately 30 mL/min. Clearance of lamotrigine is primarily metabolic with subsequent elimination of glucuronide-conjugated material in urine. Less than 10% is excreted unchanged in the urine. Only about 2% of lamotrigine-related material is excreted in faeces (Reference 102).

PBT/vPvB assessment

Lamotrigine does not fulfil the criteria for PBT and/or vBvP.

All three properties, i.e. ‘P’, ‘B’ and ‘T’ are required in order to classify a compound as PBT (Reference 1). Lamotrigine does not fulfil the criteria for PBT and/or vBvP based on log Pow < 4.

Please, also see Safety data sheets on http://www.msds-gsk.com/ExtMSDSlist.asp.

References

1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment.

2. Kent SJ and Swarbrick RH. Lamortrigine: Toxicity to the green alga Selenastrum capricornutum. Report No. BL7681/B. Brixham Environmental Laboratory, August 2004.

3. Kent SJ and Swarbrick RH. Lamortrigine: Acute Toxicity to Daphnia magna. Report No. BL7680/B. Brixham Environmental Laboratory, July 2004.

4. Young BE and Kent SJ. Lamortrigine: Determination of the 3 brood (7 day) chronic toxicity to Ceriodaphnia dubia. Report No. BL8147/B. Brixham Environmental Laboratory, March 2006.

5. Kent SJ and Swarbrick RH. Lamortrigine: Acute Toxicity to rainbow trout (Oncoryhynchus mykiss). Report No. BL7682/B. Brixham Environmental Laboratory, August 2004.

6. Lamotrigine: Activated Slude, Respiration Inhibiton Test. Test No. 91-04-232-01. AATCC Testing Services, April 1991.

7. Blasberg J. Aerobic Biodegradation in Water Using 14-C-Lamotrigine. Report No. 40510. ABC Laboratories, November 1992.

8. Stewart KM, Smyth DV, Kent SJ. Lamotrigine: Determination of Inherent Biodegradability (Zahn-Wellens test). Report No. BL7683/B. Brixham Environmental Laboratory, October 2004.

9. Lamictal Environmental Information Document. Report No. GCPV/91/0005-01. Burroughs Wellcome Co., January 1993.

10. Pharmacokinetic properties: Meatbolism and Elimination. Summary of Product Characteristics Lamictal (Lamotrigine). GlaxoSmithKline, April 2013.