Absorption, Distribution and Excretion
In rats, radiolabeled ciprodione was rapidly absorbed and excreted from the gastrointestinal tract after a single oral gavage dose of 0.5 or 100 mg/kg body weight, or repeated administration at a dose of 0.5 mg/kg body weight/day for 14 consecutive days. Following oral administration, approximately 75% (range 71-85%) of the dose was absorbed within 48 hours. At doses of 0.5 and 100 mg/kg body weight, two peaks in plasma radioactivity were observed at approximately 0.5-1 hour and 8-12 hours, likely due to reabsorption of substances excreted in bile. Approximately 92-97% of the dose was excreted within 48 hours via urine (48-68%), feces (29-47%), and bile (up to 35.4% in cannulated rats), and was almost completely cleared by day 7. Following a single or repeated oral administration of a low dose over 7 days, the total tissue residue is 0.15–0.60% of the administered dose. …Excretion, distribution, and metabolite profiles are largely independent of dose, pretreatment, and radiolabeling site, although some sex differences exist in urinary metabolites.
After oral administration, CGA 219417 is rapidly absorbed and rapidly and almost completely excreted in urine and feces. Tissue residues are generally low, and there is no evidence of radioactive accumulation or retention.
Metabolism/Metabolites

In studies of rat metabolism, …Cyproridine is primarily metabolized via hydroxylation of the benzene ring, pyrimidine ring, and methyl group, and is excreted primarily as glucuronide or sulfate conjugates in urine, feces, and bile. Approximately 3–8% of the parent compound was detected in feces. Excretion, distribution, and metabolite profiles are largely independent of dose, pretreatment, and radiolabeling site, although some quantitative sex differences exist in urinary metabolites.
The metabolic pathway is independent of sex, pretreatment, or dose level. In tomatoes, the metabolism of CGA 219417 mainly occurs through the hydroxylation of the 6-methyl group of the pyrimidine ring and the hydroxylation of the benzene ring and the pyrimidine ring.

Toxicity Summary
Identification and Uses: Cyprodinium is a pale yellow fine powder. It can be used as a foliar fungicide for cereals, grapes, pome fruits, stone fruits, strawberries, and vegetables, and also as a barley seed treatment agent. It is effective against a variety of pathogens, including Pseudocercosporella herpotrichoides, Erysiphe spp., Pyrenophora teres, Rhynchosporium secalis, and Septoria nodorum. Human Exposure and Toxicity: Cyprodinium is an aryl hydrocarbon receptor activator, a potential endocrine disruptor, and an extracellular signal-regulated kinase disruptor. Cyprodinium has a weak binding activity to androgen receptors. At a concentration of 20 μM, cycloprodinium exhibits genotoxicity in HepG2 cells. Animal studies: In a 28-day gavage study of rats, the lowest observed effect level (LOEL) was 100 mg/kg body weight/day based on increased liver weight and abnormal liver morphology. In a two-generation reproductive study of rats, the LOEL for maternal systemic toxicity was 4000 ppm (approximately 326 mg/kg/day) based on decreased body weight in F0 generation females before mating. The no observed effect level (NOEL) for maternal systemic toxicity was 1000 ppm (approximately 81 mg/kg/day). Based on decreased body weight in pups (F1 and F2 generations), the LOEL for reproductive/developmental toxicity was 4000 ppm (approximately 326 mg/kg/day). The NOEL for reproductive toxicity was 1000 ppm (approximately 81 mg/kg/day). In an 18-month mouse carcinogenicity study, the incidence of focal and multifocal hyperplasia of the exocrine pancreas in male mice increased with increasing dose, with a lowest observed effect concentration (LOEL) of 2000 ppm (212.4 mg/kg/day in male mice). The no observed effect concentration (NOEL) was 150 ppm (16.1 mg/kg/day in male mice). The test doses in this study were determined based on signs of toxicity observed in male mice at 2000 ppm and in female mice at 5000 ppm. No signs of carcinogenicity were observed at any dose level. Ecotoxicity studies: In plants, ciprofloxacin promoted massive exudate secretion and caused the most severe stigma cell disintegration among all fungicides evaluated.

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Toxicity Data
LC50 (Rat)> 1,200 mg/m3/4h

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Interactions
…A previous study identified seven of the most common pesticide mixtures that French residents were exposed to through food in 2006. This study aimed to investigate whether these seven mixtures possessed potential cytotoxicity and genotoxicity, and if so, whether compounds in the same mixture had synergistic effects. The cytotoxicity and genotoxicity of these seven mixtures were investigated using four human cell lines (ACHN, SH-SY5Y, LS-174T, and HepG2) and a novel assay (γ-H2AX). The mixtures were tested at equimolar concentrations and concentrations reflecting their actual proportions in the diet. Regardless of the cell line tested, all seven mixtures exhibited similar cytotoxicity. Only one mixture showed genotoxicity to HepG2 cells at both equimolar concentrations of 3 μM and actual proportions of 30 μM. We also used the same mixture and HepG2 cells to detect caspase 3/7 activity, comet assay, and reactive oxygen species (ROS) production. The results indicated that pesticide metabolites in the mixture produced by HepG2 cells were responsible for the observed DNA damage. Of the five compounds in the genotoxic mixture, only flufenoxuron and cyclopropamide were individually genotoxic to HepG2 cells at concentrations of 4 μM and 20 μM, respectively. Our data suggest that low-concentration mixtures have synergistic genotoxic effects, and that the combined effect of the pesticides is significantly greater than the expected effect of a single compound.

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Non-human toxicity values
Oral LD50 in rats >2000 mg/kg
Dermal LD50 in rats >2000 mg/kg
Inhalation LC50 in rats >1200 mg/m³/4 hr

[1]. Possible methionine biosynthesis inhibition by pyrimidinamine fungicides. Pestic. Sci. 42(3),163-166 (1994).

[2]. Widely used pesticides with previously unknown endocrine activity revealed as in vitro antiandrogens. Environ Health Perspect. 2011 Jun;119(6):794-800.

Cyprodinil is an aminopyrimidine compound with the structure N-phenylpyrimidine-2-amine, containing cyclopropyl and methyl substituents at positions 4 and 6, respectively. It is a broad-spectrum fungicide used to control a variety of pathogens, including Tapesia yallundae, Botrytis spp., Alternaria spp., and Rhynchospium secalis. Although Cyprodinil is somewhat irritating, no serious harm to human health has been found. It is moderately toxic to birds, most aquatic organisms, and earthworms, but non-toxic to bees. Cyprodinil can be used as an aromatic hydrocarbon acceptor agonist, an environmental pollutant, an exogenous substance, and an antifungal pesticide. It is an aminopyrimidine compound, belonging to the secondary amino group, the cyclopropane group, and also an aniline pyrimidine fungicide. Cyclopropionitrile is a fungicide that works by inhibiting germ tube elongation and hyphal growth. Cyclopropionitrile can be used to control foliar diseases in apricot, grape, stone fruit, and pome fruit crops.

C14H15N3

225.29

225.126

121552-61-2

Cyprodinil-d5;1773496-67-5;Cyprodinil-13C6;1773496-63-1

86367

White to off-white solid powder

1.2±0.1 g/cm3

406.0±48.0 °C at 760 mmHg

68 - 70ºC

199.3±29.6 °C

0.0±0.9 mmHg at 25°C

1.659

4

1

3

3

17

246

0

HAORKNGNJCEJBX-UHFFFAOYSA-N

InChI=1S/C14H15N3/c1-10-9-13(11-7-8-11)17-14(15-10)16-12-5-3-2-4-6-12/h2-6,9,11H,7-8H2,1H3,(H,15,16,17)

4-cyclopropyl-6-methyl-N-phenylpyrimidin-2-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 100 mg/mL (443.87 mM)

Solubility in Formulation 1: 2.5 mg/mL (11.10 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (11.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)