t n e evaluation of oligomers - european food safety authority · karla pfaff, 2016-05-25, efsa fip...

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Evaluation of oligomers

Dr. Karla Pfaff

Karla Pfaff, 2016-05-25, EFSA FIP Network 2

Regulation (EU) 10/2011

Art. 3

(9) ‘non-intentionally added substance’ means an impurity in the substancesused or a reaction intermediate formed during the production process or adecomposition or reaction product;

i.a. oligomers

Art. 19

… shall be assessed in accordance with internationally recognised scientificprinciples on risk assessment.

NIAS


cyclic dimer of BADGE and BPA

reaction product in epoxy resins used in can coatings

Cyclo-di-BADGE in canned fish

BADGE

+

BPA Cyclo-di-BADGE


measurements within a research project of the control laboratory inMünster.

Analytical method:- DLLME (dispersive liquid-liquid microextraction)- RP-HPLC-FLD (Method I)

NP-HPLC-FLD (Method II) for confirmation

DL LOQ

Method I 22 µg/kg 44 µg/kg

Method II 77 µg/kg 154 µg/kg



Bezeichnung

CdB [µg/kg]

Verreibung - RP-18

(alte Methode)

CdB [µg/kg]

DLLME - RP18

CdB [µg/kg]

DLLME - NP

Epoxyharz

(FTIR)

Thunfischfilets in Sonnenblumenöl n.n. neg

Heringsfilets geteilt in Tomatensauce n.n. neg

Heringsfilets in einer Tomatensauce n.n. neg

Makrelenfilets in Pflanzenöl und Saft n.n. neg

Hanseatenröllchen n.n. neg

Thunfisch in Öl n.n. neg

Feuerröllchen aus Heringsfilets n.n. neg

Heringsfilets in Tomaten Creme n.n. neg

Heringsfilets in Tomatensauce n.n. neg

Lachsfilet in Senf-Dijon-Sauce n.n. neg

Bratheringsfilets in Marinade n.n. neg

Thunfischfilets in eigenem Saft n.n. neg

zarte Heringsfilets in Mexico-Sauce n.n. neg

Bücklingsfilets in Saft und Pflanzenöl n.n. neg

Heringsfilets in Paprikasauce n.n. neg

Makrelenfilets in Tomatensauce 36 neg/?

Herings-Filets in Tomatensauce 37 neg/?

Sardinen in Tomatensauce 62 pos

Sardinen in Sonnenblumenöl 593 1326 1226 pos

Geräucherte Sprotten in Öl 1063 1848 1372 pos

Sardinen in SB-Öl 1786 1674 pos

Thunfisch in Öl 1377 1097 pos

Sardinen in SB-Öl 1714 1958 pos

Thunfisch Filets in SB-ÖL 988 797 pos

Thunfisch Filets in Öl 302 253 ?

Thunfisch in SB-ÖL 284 247 ?

Thunfisch in SB-ÖL n.n. neg

Sardinen in Öl 1893 2006 pos

Makrelenfilets in Rapsöl n.n. neg

Thunfischfilets in Sonnenblumenöl n.n. neg


Reactions from industry:- factors influencing the formation of CdB in the resin are not known, it is

therefore not possible to influence the CdB content- migration > 50 ppb is technically unavoidable



Evaluation by BfR:

Data are comparable to the results of Biedermann et al. (2013).

Experimental data on toxicokinetics, absorption (sub)chronic toxicity andgenotoxicity for CdB are missing.

A toxicological threshold cannot be derived.

Biedermann et al. (2013): From in silico assessment it can be concludedthat CdB is metabolised into linear molecules which are structurally similarto BADGE.BADGE is neither genotoxic nor carcinogenic, a transfer of CdB into foodup to 50 µg/kg was therefore regarded as preliminarily acceptable by BfRin 2011.

CdB has no structural alerts for genotoxicity and can be categorized asCramer structural class III, i. e. a daily intake of 1.5 µg/kg b.w. resp. 90µg/person is tolerable.



Evaluation by BfR:

According to the Swiss estimates (Biedermann et al., 2013), the max.concentration of 2 mg CdB/kg at an average consumption of canned fishof 3 g/person and day would result in an exposure of 0.006 mg/personand day (0.03 mg/person and day at the 95th percentile of 15 g cannedfish).

For people consuming canned fatty foodstuffs regularly in high amounts,this exposure can be exceeded and negative health effects cannot beexcluded:

A daily consumption of one can (125 g) at the max. level of 2 mgCdB/kg would result in a daily ingestion of 0.25 mg CdB per person.

To protect also this consumer group, industry should either provideexperimental data on genotoxicity and subchronic toxicity of CdB orchange to can coatings free of CdB for food in oil.



Migration of styrene oligomers

measurements within a research project of the control laboratory inMünster.

Analytical method: LC-GC-MS/MS

Sensitivity:

DL LOQ

Fat simulants 8 – 15 ng/kg 32 – 52 ng/kg

Ethanolic simulants 0.7 – 1.0 ng/kg 2.6 – 4.9 ng/kg

Tenax 0.054 – 0.103 ng/dm² 0.215 – 0.410 ng/dm²


CH2

1,3-Diphenylpropane 2,4-Diphenyl-1-butene

H

H

trans-1,2-Diphenylcyclobutane

2,4,6-Triphenyl-1-hexene

1-Phenyl-4-(1-phenylethyl)-1,2,3,4-tetrahydronaphthalene(3 of 4 isomers)

CH3

CH2

Dim

ers

Trim

ers

Migration of styrene oligomers

Substances analysed:


Sample Test conditions Σ Dimers [µg/kg] Σ Trimers [µg/kg]

Coffe to Go cup10% Ethanol, 2 h/70 °C 0,6 2,3

10 % Ethanol, 2 h/RT 1,1 2,6

Cup

10% Ethanol, 2 h/ 70 °C 2 1,7

10 % Ethanol, 2 h/RT 1,1 2,6

50 % Ethanol, 2 h/70 °C 11,7 39,4

50 % Ethanol, 2 h/RT 0,8 12,2

Cup

10% Ethanol, 2 h/70 °C 1,2 3,3

10 % Ethanol, 2 h/RT 0,7 1,6

50 % Ethanol, 2 h/70 °C 2,4 11,9

50 % Ethanol, 2 h/RT 0,3 5,5

Drinking bottle 10% Ethanol, 6 h/RT 0,3 2,2

Spray bottle forvinegar & oil

Miglyol, 10 d/RT 0,7 4,8

Sunflower oil, 10 d/RT 0,3 2,4

Beaker 10 % Ethanol, 2 h/RT 0,8 2,5

Plastic knifeMiglyol, 2 h/RT n.n. n.n.

10 % Ethanol, h/RT n.n. n.n.

Beaker10 % Ethanol, 2 h/RT 1,1 3,9

50 % Ethanol, 2 h/RT 0,4 6,3

Stemmed glass 10 % Ethanol, 2 h/RT n.n. 2

Schnaps glass10 % Ethanol, 2 h/RT n.n. n.n.

50 % Ethanol, 2 h/RT 0,4 6,8

Storage box Tenax, 10 d/ 40 °C 21,7 µg/dm² 45,3 µg/dm²

Menu boxSunflower oil, 2 h/40 °C n.n. 37,2

Tenax , h/40 °C 0,02 µg/dm² 0,2 µg/dm²

Σmax: 51,1 µg/kg

Migration of styrene oligomers - results



0

50

100

150

200

250

300

350

400

450

500

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Sum of Dimers Sum of Trimers

Migration: Sunflower oil; 24h/40 °CCell; Surface:Volume ratio = 10:1

* Surface volume ratio = 6:1

µg

/kg

oil

*

*

PS foam trays:



Preliminary evaluation by BfR:

Limited in vitro data on genotoxicity of styrene di- and trimers areavailable, which do not raise concern of genotoxicity, i. e. migration up to0.05 mg/kg can be accepted.

Data on endocrine effects are inconsistent.

From published data it can be concluded that an oral exposure of amixture styrene oligomers up to 1 mg/kg b.w. does not result in effectson reproductive function and development in rat offspring.

Migration data exceeding 0.05 mg/kg, as determined from foamedpolystyrene samples, cannot be evaluated due to lack of (sub)chronictoxicity data.


PA6 and PA66 oligomers in artificial casings and kitchen utensils

Cyclic oligomers from polyamides

1,8-Diazacyclotetradecan-2,9-dion(cyclic dimer of PA66)

Migration from artificial casings(water, 80°C/2h)430 µg/kg

1,8-Diazocyclotetradecan-2,7-dion(cyclic dimer of PA6)

Migration from kitchen utensils(water, 100°C/2h)1st test: 5 mg/dm², 3rd test: 1.5 mg/dm²(cocos fat, 220°C)10th test: 0.5 mg/dm²


Preliminary evaluation by BfR:

Both dimers can be classified into Cramer class III i.e. a daily exposure of90 µg/person resp. 1.5 µg/kg b.w. can be accepted.

• 1,8-Diazacyclotetradecan-2,9-dion (cyclic dimer of PA66):

The mean daily consumption of sausages results in an exposure of

0.4 – 0.7 µg/kg b.w./d for children and of 0.2 – 0.4 µg/kg b.w./d for adults.

The migration of from the artificial casing analysed is not expected toendanger consumers.

• 1,8-Diazocyclotetradecan-2,7-dion (cyclic dimer of PA6):The assumption that one meal per day is prepared with kitchen utensils made ofPA6 with a contact surface of 1 dm² results in an exposure of 1500µg/person.

The exposure not expected to pose a health risk is exceeded by far.



German NRL at the BfR: Investigation in 8 samples of tea bags

Characterisation of the polymer type by ATR-FTIR, validation by

pyrolysis-GC-MS:

2 samples are made from PA6 (3 samples PET, 3 samples cellulose

based)



Tea bags were tested with tea and emptied in triplicate.

Migration was tested using 200 ml tap water per bag.

Cups were filled with cooking water and let cool down for 10 min.

Quantification by LC-ESI-MS/MS, additional validation by standard

addition.



Results:


Mean concentration of PA 6 oligomers [µg/l]

Dimer Trimer Tetramer Pentamer Hexamer Heptamer Octamer Nonamer ∑

P-15-071(without tea)

41,3 116,5 129,5 103,6 57,5 20,9 9,7 4,2 483,2

P-15-071(with tea)

31,9 90,5 98,2 78,2 36,4 12,8 6,0 2,8 356,8

P-15-072(without tea)

51,6 145,9 169,6 130,8 61,7 22,5 8,2 3,6 593,9

P-15-072(with tea)

56,6 162,3 189,6 115,1 54,3 5,8 < NWG 1,3 585,0


Summary

For oligomers, data which would allow to derive toxicological thresholds are in mostcases not available.

The application of the TTC concept (Cramer classification) and of in silico assessmenttools in connection with a specific exposure assessment can be helpful .

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NT Thank you for your attention

Federal Institute for Risk Assessment

Max-Dohrn-Str. 8-10 10589 Berlin, GERMANY

www.bfr.bund.de

t n e evaluation of oligomers - european food safety authority · karla pfaff, 2016-05-25, efsa fip...

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