EXECUTIVE SUMMARY

The objectives of this risk assessment were to:

· ascertain the state of the science in research into the potential health effects of low levels of tetrahydrocannabinol (THC) and other cannabinoids found in Cannabis sativa;

· identify key health hazards that may be associated with the presence of THC and other cannabinoids in consumer products made with industrial hemp (C. sativa cultivars with <0.3% (w/w) THC);

· assess the human health safety of the Canadian limit of 10 ug/g THC for raw materials and products made from industrial hemp; and

· to identify uncertainties and critical data gaps in the risk assessment.

Of the more than 60 cannabinoids identified in C. sativa, the toxicity of THC is the best characterized. Limited toxicity data have been reported for two other cannabinoids, cannabidiol (CBD) and cannabinol (CBN), but there are no toxicity data on the remaining cannabinoids.

Two key hazards of cannabinoid exposure are neuroendocrine disruption and neurological impairment. Neuroendocrine disruption by low levels of cannabinoids during developmental stages (perinatal, prepubertal, pubertal) leads to permanent adverse effects on brain and reproductive system development in animals. The lowest observed effect level (LOEL) for neuroendocrine disruption by THC was 1 ug/kg/d derived from a study in rats (no suitable human studies were available). Such effects could occur in humans. Similarities in the types of adverse effects, the cannabinoid receptor distribution in the brain, and the pharmacokinetics and metabolism of cannabinoids among humans and animal species support the extrapolation from animal data to humans for the purposes of risk assessment. Neurological impairment is manifested as deficits in performance with respect to cognitive and motor skills. The LOEL for neurological impairment by THC was 70 ug/kg based on data from a dose-response study in which human subjects who had a history of marihuana use received a single oral dose of THC, and cognitive and motor skills and perception of psychoactive effects were measured.

It was not deemed possible to develop a tolerable daily intake (TDI) due to the lack of a no observed effect level (NOEL), lack of data on chronic exposure and lack of data on the potential contribution of other cannabinoids to the adverse effects. Potential health risks of foods made with industrial hemp ingredients were characterized by estimating the amount of food from various food categories that would need to be eaten to reach a dose of THC equal to the LOELs for neurological impairment in humans and neuroendocrine effects in animals. Potential health risks from use of cosmetics and personal care products and nutraceuticals made with industrial hemp oil were characterized by comparing exposure to

THC through product use with the LOELs for neurological impairment in humans and neuroendocrine effects in animals. These exposure estimates were based on the assumption that the THC concentration in industrial hemp-based in ingredients was 10 ug/g, the current Canadian guideline.

The direct comparison of exposure results with the LOELs does not address:

· the bioaccumulative potential of THC with repeated dosing or consumer use;

· the lack of an identified NOELfor THC for neuroendocrine disruption or neurological impairment;

· the potential that some individuals may be more sensitive to THC than the adults with a history of marihuana use for which the LOEL of 70 ug/g for neurological impairment was observed;

· the possibility that humans could be more sensitive to THC than the rats in the study used to derive the LOEL of 1 ug/kg for neuroendocrine disruption; and,

· the potential for neuroendocrine disruption or neurological impairment by other cannabinoids (i.e. CBD, CBN and others) that would be present in industrial hemp-based products (concentrations of these have not been measured).

In consideration of the above uncertainties, the conclusions from the risk characterization were as follows:
Food: Risk of neuroendocrine disruption: Likely.

Risk of neurological impairment and psychoactivity: Likely, particularly for children.

With respect to neurological impairment, the amount of each food type that would need to be consumed to deliver a dose of THC equal to the LOEL exceeded the mean daily intake and "serving size" which may suggest an absence of risk. In the case of the child; however, some foods (dairy substitutes and candy) were identified that could be consumed in sufficient quantities on occasion in a single day or a single sitting to cause neurological impairment, or even psychoactive effects. For example 2.3 ice cream bars could deliver a dose of THC of 70 ug/kg (the LOEL for neurological impairment) and 4.6 ice cream bars could deliver a dose of 140 ug/kg (the LOEL for psychoactivity) for a 33.9 kg child.

Cosmetics: Risk of neuroendocrine disruption: Possible

Risk of neurological impairment: Unlikely

The risk of neurological impairment cannot be excluded entirely, particularly in the case of children without further information on the relative sensitivities of children vs adults, the relative sensitivities of marihuana users vs non users, the effects of repeated exposure over a long time period, the effects and concentrations of cannabinoids other than THC and the extent of dermal penetration and systemic exposure of topically applied cannabinoids under conditions of actual product use.

Nutraceuticals: Risk of neuroendocrine disruption: Likely

Risk of neurological impairment: Possible, particularly in children.

Major shortcomings related to key data gaps identified in the assessment that preclude the development of definitive conclusions regarding the degree of potential risk are:

· the inability to consider the potential contribution of cannabinoids other than THC (limited toxicity data for other cannabinoids indicate their ability to cause neuroendocrine disruption) to the overall health risks;

· the inability to consider the long term effects of bioaccumulation of THC over time from repeated low dose exposure due to lack of chronic low level toxicity studies and lack of data on the steady-state pharmacokinetics of THC;

· the inability to consider the effects of THC and other cannabinoids after multi-generation long term exposure;

· the inability to determine the degree of exposure to the developing fetus and nursing infant; and

· the lack of analytical data for THC and other cannabinoid concentrations, at detectable levels, in raw materials and finished products made from industrial hemp.