Guidelines for Canadian Drinking Water Quality: Guideline Technical Document – Simazine

The theoretical maximum daily intake of simazine from food is 0.02 mg/d, based on the residue tolerance limits set by the Food Directorate of the Department of National Health and Welfare.^{Footnote 10} No information on the actual intake of simazine was found. Standard residue trials conducted in several countries revealed that residues in harvested crops were usually less than 0.04 mg/kg. Exceptions were asparagus, which was found to contain 0.13 mg/kg simazine, and maize forage, which contained 0.35 mg/kg, seven days after application of 4.4 kg active ingredient per hectare. Residues in beef, mutton and milk were less than 0.1 mg/kg (the Canadian negligible residue limit),^{Footnote 10} following diets containing 100 ppm simazine.^{Footnote 7}

Analytical Methods and Treatment Technology

Simazine in water may be determined by extraction with chloroform, separation by gas/liquid chromatography and detection by electrolytic conduction, nitrogen mode (detection limit 0.2 µg/L).^{Footnote 8} An alternative method involves extraction into dichloromethane, gas chromatographic capillary column separation and nitrogen phosphorus detection (estimated detection limit 0.1 to 2 µg/L).^{Footnote 11}

Conventional treatment processes are reported to be relatively ineffective in removing simazine from drinking water supplies.^{Footnote 11} A 44% reduction in simazine concentration has been reported following treatment of water with an initial simazine concentration of 480 ng/L by powdered activated carbon adsorption in St.Hyacinthe, Quebec.^{Footnote 12} Powdered activated carbon adsorption has also been reported to result in 43 to 100% removal of simazine from water, whereas granular activated carbon adsorption has resulted in 35 to 89% removal (initial concentrations not reported).^{Footnote 11} Other treatment methods investigated for efficiency in simazine removal (initial concentrations not reported) are ion-exchange resins (81 to 95%), chlorine oxidation (17 to 74%, depending on dose), chlorine dioxide oxidation (8 to 27%), ozonation (92% in spiked, distilled water), oxidation (19 to 42% in spiked, distilled water with hydrogen peroxide, 1 to 25% in spiked river water) and potassium permanganate oxidation (up to 26% in spiked, distilled water).^{Footnote 11}

Health Effects

Little information is available on the extent of absorption of ingested simazine. Four days following administration by stomach tube of 0.8 mg radioactively labelled simazine in 1 mL arachis (peanut) oil to Carworth Farm E strain rats, 91.9 (males) to 94.5% (females) was recovered; 40.6% was eliminated via the urine, 47.2% was recovered in the faeces, and 3% of the dose remained in the animal tissues. N-dealkylation and mercapturic acid formation were the major routes of metabolism,^{Footnote 13 Footnote 14} with major urinary metabolites being N-acetyl-S-[4-amino-6-(1-methyl-1-cyanoethylamino)-s-triazinyl-2]-L-cysteine and 2-chloro-4-amino-6-(1-methyl-1-cyanoethylamino)-s-triazine.^{Footnote 13}

No reports on the toxicity of simazine ingested by humans were identified, although skin contact has caused dermatitis.^{Footnote 14} Simazine is considered to be only slightly acutely toxic to mammals.^{Footnote 7}

In a two-year dietary study in Charles River rats (30 per sex per dose), animals were administered 0, 1, 10 or 100 ppm simazine in the feed. No signs of toxicity were observed at any dose level, and no differences were noted between treated and control animals upon gross pathological and histopathological examination. The no-observed-adverse-effect level (NOAEL) was considered to be above 100 ppm,^{Footnote 15} which is equivalent to 5 mg/kg bw per day.^{Footnote 11} This study is very limited for the derivation of a NOAEL because of the very high mortality from unreported causes (50 to 82% for various groups).^{Footnote 7}

Dogs (two males and two females per dose group, strain unspecified) were fed diets containing 0, 15, 150 or 1500 ppm for up to two years, with two animals per group being sacrificed after 52 weeks for detailed pathological examination. Dogs receiving 1500 ppm had slightly lower body weights; marginally higher levels of serum alkaline phosphatase and serum glutamic-oxaloacetic transaminase were also noted sporadically in these animals after 84 or 104 weeks of treatment. A slight hyperplasia of the thyroid gland was also observed in the highest dose group. No other compound-related differences were noted based on urinalysis, gross autopsy or histopathological examination. The NOAEL for dogs was considered to be 150 ppm, which was reported to be equivalent to 5 mg/kg bw per day.^{Footnote 7}

Simazine was not tumorigenic in a limited 18-month study in which hybrid mice were administered doses of 215 mg/kg bw by gavage from ages 7 to 18 days, followed by a daily diet containing 215 mg/kg bw per day.^{Footnote 16} Another study in mice (Swiss-CD-1 strain), in which there were no significant increases in tumour incidence in 60 animals per sex per dose exposed to simazine (doses of 0, 15, 1000 and 3000 ppm, route unspecified) for 21 months, was judged inadequate for assessment of carcinogenicity because of the loss by autolysis of a large number of animal tissues.^{Footnote 7}

Simazine was not mutagenic in several microbial assay systems.^{Footnote 11} It induced lethal mutations in the sex-linked recessive lethal test in Drosophila melanogaster;^{Footnote 17} an elevation in X-linked lethals was induced by injection of simazine into male D. melanogaster.^{Footnote 18} Both positive^{Footnote 19} and negative^{Footnote 20} results have been reported for the induction of unscheduled DNA synthesis in human lung fibroblasts. Based on results from an additional six in vivo and in vitro assays, it was concluded that neither simazine nor its metabolites showed any mutagenic potential.^{Footnote 7}

In three studies in rats, no teratogenic effects were noted at levels below those that produced maternal toxicity. Pregnant rats received doses of simazine of up to 600 mg/kg bw per day by intubation on days 6 to 15 of gestation. Both maternal toxicity and foetotoxicity were observed at dose levels of 100 mg/kg bw per day and above. Observed adverse effects included an increased incidence of aborted foetuses and embryonic resorptions, along with hypoplastic lungs, reduced pup weight and vitality and increased incidence of skeletal variations, such as non-ossification of the sternebrae.^{Footnote 7} Simazine was not teratogenic at maternally non-toxic doses in rabbits exposed to 5, 75 or 200 mg/kg bw per day during gestation.^{Footnote 7}

No adverse reproductive effects were observed in a three-generation study in albino Charles River rats receiving 50 or 100 ppm simazine in the diet. The NOAEL for this study was considered to be 100 ppm, or 5 mg/kg bw per day.^{Footnote 7}

Rationale

The Food Directorate of the Department of National Health and Welfare has derived a negligible daily intake (NDI) for simazine as follows:

NDI = 5 mg/kg bw per day ÷ 4000 ≈ 0.0013 mg/kg bw per day

where:

• 5 mg/kg bw per day is the NOAEL from a two-year study in dogs^{Footnote 7}
• 4000 is the uncertainty factor.

The maximum acceptable concentration (MAC) for simazine in drinking water is derived from the NDI as follows:

MAC = 0.0013 mg/kg bw per day × 70 kg × 0.20 ÷ 1.5 L/d ≈ 0.01 mg/L

where:

• 0.0013 mg/kg bw per day is the NDI derived by the Food Directorate
• 70 kg is the average body weight of an adult
• 0.20 is the proportion of daily intake of simazine allocated to drinking water
• 1.5 L/d is the average daily consumption of drinking water for an adult.

References