Insulin DesB30

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

(Human Insulin Methyl Ester S5)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read Across please refer to section "justification for type of information"

Justification for type of information:

The aquatic toxicity of Insulin DesB30 to fish is assumed to follow the same pattern as that of the source substance because of the high degree of structural similarity:
• Insulin DesB30 and the source substance belong to the same chemical categories: human insulins, polypeptides and proteins
• Insulin DesB30 and the source substancs are composed of polypeptide containing amino acids

Please refer to Environmental Assessment Reports (Section 13)

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

> 30.1 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 30.1 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Validity criteria fulfilled:

not applicable

Conclusions:

The aquatic toxicity of Insulin DesB30 is assumed to be similar to the source substance (S5) because of the high degree of structural similarity.
•       Insulin DesB30 and the source substance belong to the same chemical categories: human insulins, polypeptides and proteins
•       Insulin DesB30 and the source substancs are composed of polypeptide containing amino acids

No effects to invertebrates were observed during the study with Insulin Human Methyl Ester (S5) and an EC10 and EC50 (48h) of > 30.1 mg/L (geom. mean) were determined.

Executive summary:

The aquatic toxicity of Insulin DesB30 is assumed to be similar to the source substance (S5) because of the high degree of structural similarity.

•       Insulin DesB30 and the source substance belong to the same chemical categories: human insulins, polypeptides and proteins

•       Insulin DesB30 and the source substancs are composed of polypeptide containing amino acids

No effects to invertebrates were observed during the study with Insulin Human Methyl Ester (S5) and an EC10 and EC50 (48h) of > 30.1 mg/L (geom. mean) were determined.

Insulin DesB30 is predicted to have a toxicity to invertebrates with LC10 and LC50 of > 30.1 mg/L based on the results from the study with Insulin Human Methyl Ester.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

2004.04.13

Deviations:

no

Qualifier:

according to guideline

Guideline:

ISO 6341 (Water quality - Determination of the Inhibition of the Mobility of Daphnia magna Straus (Cladocera, Crustacea))

Version / remarks:

2012.12.18

GLP compliance:

yes

Specific details on test material used for the study:

The test item is an intermediate. Based on information from the sponsor, the test item is:

The test item is: Hi-OMe (Human Insulin Methylester)

Chemical name: Zinc crystals of HI-OMe
CAS No: Not applicable
Molecular formula: C258H385N65O77S6
Purity: 95-98%
Impurities: Derivatives of HI-OMe, desB30-Insulin, Insulin Human
Percentage of (significant) main impurities:
Typical Concentration: <3.0 % w/w
Concentration Range: 2.0 – 5.0 % w/w
Form: White powder
Water solubility: Dependent of pH
Log Pow: Not possible to perform

Batch Number: EM0Z31503
Manufacturing date: 27.11.2016
Stability: In aqueous solution, stable up to 96 hours at 4°C
Origin: Novo Nordisk A/S

Analytical monitoring:

yes

Details on sampling:

Duplicate samples of 5 mL ((0hr, 24hr, 48hr) were collected in 20 mL plastic vials and stored at -20.0 °C

Vehicle:

no

Test organisms (species):

Daphnia magna

Details on test organisms:

Juvenile organisms < 24 h old at the beginning of the test

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Remarks on exposure duration:

renewal of test solution after 24 hours

Post exposure observation period:

not included

Hardness:

272 mg CaCO3/L

Test temperature:

19.3 ± 0.1°C

pH:

8.1

Salinity:

n.a.

Conductivity:

n.a.

Nominal and measured concentrations:

Nominal: 0 (control); 20; 40; 75; 150; 300 mg/L
Only the control and the nominal concentrations 20mg/L; 75 mg/L and 300 mg/L were analysed
Meassured (geom. mean concentration): 0.5; 10.5; 19.4; 30.1 mg/L

Details on test conditions:

Test substance: nominal concentrations: 0 (control); 20; 40; 75; 150; 300 mg/L
Reference substance: K2Cr2O7: 0.2; 0,4; 0.7; 1.0; 1.4; 1.7 and 2.0 mg/L

Reference substance (positive control):

yes

Remarks:

K2Cr2O7

Key result

Duration:

48 h

Dose descriptor:

LC10

Effect conc.:

> 30.1 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other:

Remarks:

no effects were observed during the study

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 30.1 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other:

Remarks:

no effects were observed during the study

Details on results:

As no effect was observed the EC values are reported as greater than the highest tested concentration (> 300 mg/L, nominal concentration)

Results with reference substance (positive control):

Potassium dichromate (K2Cr2O7)
EC50 (24h) = 1.2 [1.1-1.4] mg/L

Validity criteria fulfilled:

yes

Conclusions:

No mortality was observed during the study and an EC10 (48h) and EC50 (48h) > 30.1 mg/L (geom. mean) were determined.

Executive summary:

A Daphnia sp. acute immobilisation test (according to OECD Guideline no. 202) and following was conducted applying daphnids <24h old. The study was conducted according to GLP.

Concentrations were not within 20% of the nominal concentration throughout the study. And endpoints are thus reported as geometric mean concentrations (geom. mean conc.)

Organisms were exposed to the test item for 48h and since no effects were observed during the study an EC10 and EC50 (48h) > 30.1 mg/L (geom. mean) were determined.

Description of key information

The ecotoxicity of Insulin DesB30 is assumed to be simmilar to the source substance (S5) because of the high degree of structural similarity.

No mortality towards invertebrates was observed during the study with Insulin Human Methyl Ester (S5) and an EC10 and an EC50 value are therefore reported as > 30.1 mg/L (geometric mean concentration).

Insulin DesB30 is predicted to have a toxicity towards invertebrates of > 30.1 mg/L (geometric mean concentration).

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

30.1 mg/L