New substances: risk assessment, New Substances Notification 21233

Name of company and contact: Future Fields

First day of assessment period: November 18, 2022

Last day of assessment period: July 15, 2023 (due to extension of the assessment period)

Identity: A genetically modified Drosophila melanogaster strain with a single insert of a transgenic cassette encoding the gene for bovine FGF2 and a marker gene balanced over a chromosome balancer

Organism type: Insect

Use: Production of bovine fibroblast growth factor 2 (BvFGF2) for use as a supplement for growing cells in vitro for research and development purposes

Anticipated quantity: Approximately 1 100 to 1 400 kg of the notified organism is expected to be manufactured in the first 12 months with an estimated annual maximum of 3 156 kg

Assessment level of concern:

Assessment conclusion under section 64 of the Canadian Environmental Protection Act, 1999: Not toxic

Recommended action: None

Waiver: Requested under paragraph 106(8)(a) of the Canadian Environmental Protection Act, 1999 for information element 5(a) of Schedule 5 of the New Substances Notification Regulations (Organisms) [the data from a test conducted to determine its pathogenicity, toxicity or invasiveness]

Synopsis

Drosophila melanogaster strain 1 is a genetically modified fruit fly that was notified to the New Substances program for use in the production of bovine growth factor (BvFGF2).

A waiver to submit the data from a test conducted to determine the pathogenicity, toxicity, or invasiveness of the notified strain under paragraph 5(a) of Schedule 5 of the New Substances Notification Regulations (Organisms) was granted under paragraph 106(8)(a) of the Canadian Environmental Protection Act, 1999 (CEPA) given the long history of safe use of D. melanogaster and the lack of any identified toxin or virulence genes in the organism or its specific genetic modifications.

Through information available to the program and the evaluation of information submitted by the notifier, the risk assessment concluded that the hazard potential and the exposure potential to the Canadian environment and to human health from the manufacture of the notified organism is low.

It is determined that the notified strain is not toxic or capable of becoming toxic according to the criteria under section 64 of the Act as there is no evidence to suggest that the notified organism may enter the environment in a quantity or concentration or under conditions that:

No risk management is recommended.

This assessment was subject to a scientific expert peer review external to the New Substances program.

Drosophila melanogaster strain 1: background information

As a species, D. melanogaster has an extensive history of safe use in research and development. It is not known to have adverse effects on other species present in the natural environment nor is it known to be a vector for disease. The D. melanogaster strain 1 is a line of genetically modified (GM) fruit fly to be used to produce bovine fibroblast growth factor 2 (BvFGF2). The notified line is derived from a common and commercially available laboratory strain of D. melanogaster and will be manufactured under controlled conditions in a single contained facility in Edmonton, Alberta. The produced recombinant protein will be used as a growth medium supplement in cell culture.

Hazard assessment

The environmental hazard potential of D. melanogaster strain 1 is assessed to be low because:

1) The D. melanogaster strain 1 manufacturing process is well characterized and does not pose any concerns to the Canadian environment.

2) The potential for the D. melanogaster strain 1 to impact prey and competitor community dynamics through altered appetite, behaviour, and possible habitat use at different life stages if released outside of containment is expected to result in a low hazard to biodiversity.

3) All materials and substances used in the genetic insert are not known to have pathogenic or toxic effects on the notified strain nor on other species present in the natural environment. 

4) The expressed protein BvFGF2 is not known to have pathogenic or toxic effects on the notified strain nor on other species present in the natural environment. 

The human hazard potential of D. melanogaster strain 1 is assessed to be low because:

1) D. melanogaster strain 1 is a GM fruit fly derived from a commonly used laboratory strain which is not known to be associated with any hazards to humans.

2) The methods used to produce the notified living organism do not raise any human health concerns. None of the source (donor) organisms from which the inserted genetic material was derived are known to produce toxins, nor is the genetic material or BvFGF2 protein associated with any toxicity or pathogenicity in humans.

3) While wild D. melanogaster have been reported to harbour opportunistic human pathogens, there are no reported cases of zoonotic infections attributed to the species.

4) The expressed BvFGF2 protein is not expected to be toxic or allergenic as it is not structurally similar to any known allergens or toxins.

Hazards related to organisms used in the workplace should be classified accordingly under the Workplace Hazardous Materials Information System (WHMIS)Footnote 1 .

Exposure assessment

The environmental exposure potential of D. melanogaster strain 1 is assessed to be low because:

1) The notified organism is intended for use as a living insect bioreactor to produce recombinant proteins inside a controlled manufacturing facility and is not intended for release into the environment. There are no other foreseeable potential uses for the notified strain outside of the intended use, as the genetic modification leads to the expression of a single protein for use as a growth medium supplement in cell culture.

2) The containment and operating procedures that the notifier has put in place at the facility are sufficient to ensure containment of the notified organism. Maximum exposure (i.e., without containment) of D. melanogaster strain 1 to the environment was assessed to be low risk. This is because, if released, the notified organism has been genetically modified with curly wings such that it would reduce its ability to fly, and in turn would decrease its ability to find food or mates or escape predators. This reduced fitness is another layer of protection to prevent the notified organism from establishing in natural settings at the population level under the unlikely scenario of it being released.

3) The BvFGF2 genes are recessive and are inherited along with the dominant curly wing trait. This would cause a reduction in frequency across the population if in the unlikely event reproduction with wild type were to occur. Moreover, expression of the BvFGF2 protein is lost over time (typically observed from generation three to eight over a four-month period).

4) Regular checks of the physical characteristics and genetic make-up are done to ensure stocks remain uncontaminated from external or internal sources.

5) Once harvested, the notified organism will be euthanized and the expressed BvFGF2 protein extracted for use in cell culture media.

The human exposure potential of D. melanogaster strain 1 is assessed to be low because:

1) The main source of human exposure to the notified organism is expected to be occupational exposure from the manufacture of D. melanogaster strain 1 in a contained facility located in Edmonton, Alberta.

2) The D. melanogaster strain 1 is not intended for release into the environment from the facility. Containment measures in place are expected to prevent releases, and notified organism will be euthanized and the expressed BvFGF2 protein extracted for use in cell culture media. The general population is therefore not expected to be exposed to live strain 1 fruit flies.

3) In the unlikely event of an inadvertent release, human exposure, if any, is expected to be limited given the genetic modifications of the D. melanogaster strain 1 (i.e., curly wings), would reduce the notified organism’s ability to fly, reproduce, and survive in the wild. In addition, wild type fruit flies already live in close association with humans without any reported cases of adverse effects.

Risk characterization

Owing to the low potential hazard and the low potential exposure, the environmental and human health risks associated with the use of D. melanogaster strain 1 for production of BvFGF2 are both low.

Risk assessment conclusion

There is no evidence to suggest a potential a risk of adverse environmental and human health effects at the exposure levels predicted for the Canadian environment and general population from production of BvFGF2. The risk to the environment associated with D. melanogaster strain 1 is not suspected to meet criteria in paragraphs 64(a), (b), or (c) of the Canadian Environmental Protection Act, 1999. No further action is recommended.

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