3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Long-term toxicity to fish

Administrative data

Endpoint:

fish early-life stage toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

<=2017

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

fish embryo acute toxicity (FET)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

<=2017

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

A short-term toxicity test with embryos and larvae of Zebrafish is described, reporting a low toxicity.

Executive summary:

7 -ACA and other impurities of cefazolin were investigated in embryos and larvae of Zebrafish after exposure for 3 days.

The lowest LC10 of 0.88 mmol/L corresponds to 240 mg/L and was found for larvae.

The lowest LC50 of 1.32 mmol/L corresponds to 359 mg/L and was found for larvae.

The teratogenic phenotypes after exposure to 7-ACA are smaller head and eyes, poor transparency, and the short body.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2017

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 212 (Fish, Short-term Toxicity Test on Embryo and Sac-Fry Stages)

Principles of method if other than guideline:

Fish embryos and larvae were investigated for short exposure time. 7-ACA and other impurities of Cefazolin were investigated.

GLP compliance:

not specified

Remarks:

The study was performed in China by a research group.

Test material

Test material information

Constituent 1

Reference substance name:

3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

EC Number:

213-485-0

EC Name:

3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Cas Number:

957-68-6

Molecular formula:

C10H12N2O5S

IUPAC Name:

3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Provided by the National Institutes for Food and Drug Control of China. The structure of each impurity was confirmed by MS and NMR; the HPLC normalized purity was >93%.

Sampling and analysis

Analytical monitoring:

not specified

Test solutions

Vehicle:

no

Details on test solutions:

The test substance solution was prepared in breeding water. Zebrafish breeding water was prepared with Instant Ocean sea salt.

Test organisms

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Details on test organisms:

Zebrafish wild type (WT) embryos at 6 hours post-fertilisation (hpf) and larvae at 3 days post-fertilisation (dpf) were used.

Study design

Test type:

semi-static

Water media type:

saltwater

Limit test:

no

Total exposure duration:

3 d

Remarks on exposure duration:

Organogenesis occurs at period of 6–72 hpf.

Post exposure observation period:

no.

Test conditions

Hardness:

Not specified.

Test temperature:

Not specified.

pH:

Not specified.

Dissolved oxygen:

Not specified.

Salinity:

Yes.

Conductivity:

Not specified.

Nominal and measured concentrations:

Not specified.

Details on test conditions:

Both embryos and larvae were immersed, respectively, in 3–4 mL of the drug testing solutions (drugs were dissolved in breeding water) in a 20-mm dish for 3 days (organogenesis at period of 6–72 hpf), but the solutions for the treatment of the larvae were replaced every 24 h, and zebrafish were observed under a microscope. Three or four concentrations for the administered groups were used for each compound.

Reference substance (positive control):

no

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

3 d

Dose descriptor:

other: Toxic dose TD10

Effect conc.:

2.6 mmol/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: embryotoxicity

Effect concentrations 2

Duration:

3 d

Dose descriptor:

other: TD50 (toxic dose)

Effect conc.:

9.3 mmol/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: embryotoxicity

Effect concentrations 3

Duration:

3 d

Dose descriptor:

LC10

Effect conc.:

16.8 mmol/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks:

of embryos

Effect concentrations 4

Duration:

3 d

Dose descriptor:

LC50

Effect conc.:

48.7 mmol/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks:

of embryos

Effect concentrations 5

Duration:

3 d

Dose descriptor:

LC10

Remarks:

Larval lethality

Effect conc.:

0.88 mmol/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks:

of larvae

Effect concentrations 6

Duration:

3 d

Dose descriptor:

LC50

Remarks:

mortality of larvae

Effect conc.:

1.32 mmol/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks:

of larvae

Details on results:

The lowest LC10/TD10 of 0.88 mmol/L corresponds to 240 mg/L.
The lowest LC50/TD50 of 1.32 mmol/L corresponds to 359 mg/L.
The teratogenic phenotypes after exposure to 7-ACA are smaller head and eyes, poor transparency, and the short body.

Applicant's summary and conclusion

Executive summary:

7 -ACA and other impurities of cefazolin were investigated in embryos and larvae of Zebrafish after exposure for 3 days.

The lowest LC10 of 0.88 mmol/L corresponds to 240 mg/L and was found for larvae.

The lowest LC50 of 1.32 mmol/L corresponds to 359 mg/L and was found for larvae.

The teratogenic phenotypes after exposure to 7-ACA are smaller head and eyes, poor transparency, and the short body.