Hazardous Substances Data Bank s2

Hazardous Substances Data Bank,

National Library of Medicine, Bethesda, MD.

http://toxnet.nlm.nih.gov/

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TRIADIMEFON

CASRN: 43121-43-3

For other data, click on the Table of Contents

Human Health Effects:

Human Toxicity Excerpts:

Overexposures of humans are said to have resulted in hyperactivity followed by sedation.

[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare 154]**PEER REVIEWED**

Skin, Eye and Respiratory Irritations:

It causes irritation if eyes are contaminated.

Probable Routes of Human Exposure:

Occupational exposure to triadimefon occurs through dermal contact and inhalation of sprays, especially to workers applying the compound as a pesticide(1). Dermal exposure to triadimefon is reported to occur in tree nursery workers who handle triadimefon pesticides(2). Since triadimefon has been detected occasionally in the U.S. foods (3), limited exposure to the general population may occur through consumption of foods containing triadimefon residues (SRC).

[(1) Parmeggiani L; Encycl Occup Health and Safety 3rd ed. Geneva, Switzerland: International Labor Office pp. 1616-46 (1983) (2) Lavy TL et al; Arch Environ Contam Toxic 24: 123-44 (1993) (3) Yess NJ et al; J AOAC International 74: 273-80 (1991)]**PEER REVIEWED**

In a year-long study to evaluate exposure of tree nursery workers to various pesticides, exposure to triadimefon was confirmed via detections in hand rinses and patches attached to clothing(1); some exposure occurred in all four categories of worker types (applicators, weeders, scouts, packers)(1); in one tree nursery using triadimefon, positive patch detections occurred in 12 of 261 patches analyzed with a max and avg concn of 63.33 and 10.08 mg/patch, respectively(1).

[(1) Lavy TL et al; Arch Environ Contam Toxicol 24: 123-44 (1993)]**PEER REVIEWED**

The rate of decay of triadimefon and its concentration after application was measured during cucumber cultivation in greenhouses under normal growing conditions(1). In preliminary experiments, the concentration of triadimefon in air was, at a sampling period of 0-2 hours after application, below the detection limit (3 ug/cu m). Hence, air exposure is likely of no concern with respect to human health. On the floor surfaces, the triadimefon concentrations were on average 0.010 ug/sq cm after low-volume spraying and 0.013 ug/sq cm after high-volume spraying. Six days after low-volume spraying, the concentration of triadimefon was below the detection limit (0.002 ug/sq cm), and after high-volume spraying, the concentration of triadimefon was estimated to be 0.004 ug/sq cm(1).

[(1) Nilsson, U et al; J Agric Food Chem 44: 2878-2884 (1996)]**PEER REVIEWED**

Body Burden:

It has been reported that low levels of triadimefon metabolites have been detected in the urine of workers using triadimefon(1).

[(1) Wang GM; Teratog Carcinog Mutagen 8: 117-26 (1988)]**PEER REVIEWED**

Emergency Medical Treatment:

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The following Overview, *** GENERAL OR UNKNOWN CHEMICAL ***, is relevant for this HSDB record chemical.

Life Support:

o This overview assumes that basic life support measures

have been instituted.

Clinical Effects:

0.2.1 SUMMARY OF EXPOSURE

0.2.1.1 ACUTE EXPOSURE

A) A SPECIFIC REVIEW on the clinical effects and treatment

of individuals exposed to this agent HAS NOT YET BEEN

PREPARED. The following pertains to the GENERAL

EVALUATION and TREATMENT of individuals exposed to

potentially toxic chemicals.

B) GENERAL EVALUATION -

1) Exposed individuals should have a careful, thorough

medical history and physical examination performed,

looking for any abnormalities. Exposure to chemicals

with a strong odor often results in such nonspecific

symptoms as headache, dizziness, weakness, and nausea.

C) IRRITATION -

1) Many chemicals cause irritation of the eyes, skin, and

respiratory tract. In severe cases respiratory tract

irritation can progress to ARDS/acute lung injury,

which may be delayed in onset for up to 24 to 72 hours

in some cases.

2) Irritation or burns of the esophagus or

gastrointestinal tract are also possible if caustic or

irritant chemicals are ingested.

D) HYPERSENSITIVITY -

1) A number of chemical agents produce an allergic

hypersensitivity dermatitis or asthma with

bronchospasm and wheezing with chronic exposure.

Laboratory:

A) A number of chemicals produce abnormalities of the

hematopoietic system, liver, and kidneys. Monitoring

complete blood count, urinalysis, and liver and kidney

function tests is suggested for patients with significant

exposure.

B) If respiratory tract irritation or respiratory depression

is evident, monitor arterial blood gases, chest x-ray,

and pulmonary function tests.

Treatment Overview:

0.4.2 ORAL EXPOSURE

A) GASTRIC LAVAGE

1) Significant esophageal or gastrointestinal tract

irritation or burns may occur following ingestion. The

possible benefit of early removal of some ingested

material by cautious gastric lavage must be weighed

against potential complications of bleeding or

perforation.

2) GASTRIC LAVAGE: Consider after ingestion of a

potentially life-threatening amount of poison if it can

be performed soon after ingestion (generally within 1

hour). Protect airway by placement in Trendelenburg and

left lateral decubitus position or by endotracheal

intubation. Control any seizures first.

a) CONTRAINDICATIONS: Loss of airway protective reflexes

or decreased level of consciousness in unintubated

patients; following ingestion of corrosives;

hydrocarbons (high aspiration potential); patients at

risk of hemorrhage or gastrointestinal perforation;

and trivial or non-toxic ingestion.

B) ACTIVATED CHARCOAL

1) Activated charcoal binds most toxic agents and can

decrease their systemic absorption if administered soon

after ingestion. In general, metals and acids are

poorly bound and patients ingesting these materials

will not likely benefit from activated charcoal

administration.

a) Activated charcoal should not be given to patients

ingesting strong acidic or basic caustic chemicals.

Activated charcoal is also of unproven value in

patients ingesting irritant chemicals, where it may

obscure endoscopic findings when the procedure is

justified.

2) ACTIVATED CHARCOAL: Administer charcoal as a slurry

(240 mL water/30 g charcoal). Usual dose: 25 to 100 g

in adults/adolescents, 25 to 50 g in children (1 to 12

years), and 1 g/kg in infants less than 1 year old.

C) DILUTION -

1) Immediate dilution with milk or water may be of benefit

in caustic or irritant chemical ingestions.

2) DILUTION: Immediately dilute with 4 to 8 ounces (120 to

240 mL) of water or milk (not to exceed 4 ounces/120 mL

in a child).

D) IRRITATION -

1) Observe patients with ingestion carefully for the

possible development of esophageal or gastrointestinal

tract irritation or burns. If signs or symptoms of

esophageal irritation or burns are present, consider

endoscopy to determine the extent of injury.

E) OBSERVATION CRITERIA -

1) Carefully observe patients with ingestion exposure for

the development of any systemic signs or symptoms and

administer symptomatic treatment as necessary.

2) Patients symptomatic following exposure should be

observed in a controlled setting until all signs and

symptoms have fully resolved.

0.4.3 INHALATION EXPOSURE

A) DECONTAMINATION -

1) INHALATION: Move patient to fresh air. Monitor for

respiratory distress. If cough or difficulty breathing

develops, evaluate for respiratory tract irritation,

bronchitis, or pneumonitis. Administer oxygen and

assist ventilation as required. Treat bronchospasm with

inhaled beta2 agonist and oral or parenteral

corticosteroids.

B) IRRITATION -

1) Respiratory tract irritation, if severe, can progress

to pulmonary edema which may be delayed in onset up to

24 to 72 hours after exposure in some cases.

C) ACUTE LUNG INJURY -

1) ACUTE LUNG INJURY: Maintain ventilation and oxygenation

and evaluate with frequent arterial blood gas or pulse

oximetry monitoring. Early use of PEEP and mechanical

ventilation may be needed.

D) BRONCHOSPASM -

1) If bronchospasm and wheezing occur, consider treatment

with inhaled sympathomimetic agents.

E) OBSERVATION CRITERIA -

1) Carefully observe patients with inhalation exposure for

the development of any systemic signs or symptoms and

administer symptomatic treatment as necessary.

2) Patients symptomatic following exposure should be

observed in a controlled setting until all signs and

symptoms have fully resolved.

0.4.4 EYE EXPOSURE

A) DECONTAMINATION: Irrigate exposed eyes with copious

amounts of room temperature water for at least 15

minutes. If irritation, pain, swelling, lacrimation, or

photophobia persist, the patient should be seen in a

health care facility.

0.4.5 DERMAL EXPOSURE

A) OVERVIEW

1) DERMAL DECONTAMINATION -

a) DECONTAMINATION: Remove contaminated clothing and wash

exposed area thoroughly with soap and water. A

physician may need to examine the area if irritation

or pain persists.

2) PESTICIDES -

a) DECONTAMINATION: Remove contaminated clothing and

jewelry. Wash the skin, including hair and nails,

vigorously; do repeated soap washings. Discard

contaminated clothing.

3) IRRITATION -

a) Treat dermal irritation or burns with standard topical

therapy. Patients developing dermal hypersensitivity

reactions may require treatment with systemic or

topical corticosteroids or antihistamines.

4) DERMAL ABSORPTION -

a) Some chemicals can produce systemic poisoning by

absorption through intact skin. Carefully observe

patients with dermal exposure for the development of

any systemic signs or symptoms and administer

symptomatic treatment as necessary.

Range of Toxicity:

A) No specific range of toxicity can be established for the

broad field of chemicals in general.

[Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2004; CCIS Volume 122, edition expires Nov, 2004. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2004; CCIS Volume 122, edition expires Nov, 2004.]**PEER REVIEWED**

Animal Toxicity Studies:

Non-Human Toxicity Excerpts:

Ornamentals may be damaged if used at excessive rates.

[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994. 1000]**PEER REVIEWED**

Triadimefon is a fungicide that has recently been shown to incr motor activity & rates of schedule-controlled responding. These findings indicate that triadimefon resembles psychomotor stimulants & in this respect is a unique pesticide. The present experiment was designed to evaluate triadimefon's effects on performance maintained by a multiple schedule of reinforcement & to compare triadimefon to known psychomotor stimulants. Four rats were trained to perform under a multi- FI 1-min & FI 5-min schedule of milk reinforcement. They then received a series of dosages of triadimefon (10-170 mg/kg, ip) & of methylphenidate (1-17.3 mg/kg, ip) in a counterbalanced order. Triadimefon increased response rates in both the FI 1-min & FI 5-min components. Methylphenidate did not consistently alter response rates in either component. Temporal patterns of responding were disrupted much more in the FI 5-min component than in the FI 1-min component by both triadimefon & methylphenidate. Performances were then evaluated following a series of dosages of d-amphetamine (0.3-3.0 mg/kg, ip) & chlorpromazine (0.5-2.0 mg/kg, ip). Response rates were increased by d-amphetamine in the FI 1-min component but not in the FI 5-min component. Like triadimefon & methylphenidate, d-amphetamine produced a greater disruption of response patterning in FI 5-min than in FI 1-min. Only chlorpromazine decreased response rates in both components. Chlorpromazine also disrupted FI 5-min response patterning, but left FI 1-min patterning intact. Although triadimefon did not closely resemble any of the comparison drugs, it had opposite effects on response rates from chlorpromazine in both components of the schedule & resembled d-amphetamine in its effects on FI 1-min response rates. The rate-increasing effects frequently obtained with psychomotor stimulants were more evident for triadimefon than for either methylphenidate or d-amphetamine.

[Allen AR, Macphail RC; Pharmacol Biochem Behav 40 (4): 775-80 (1991)]**PEER REVIEWED**

Eight pesticides were tested in a medium-term bioassay based upon the induction of preneoplastic lesions in the liver. Rats were initially given diethylnitrosamine ip at a dose of 200 mg/kg body weight and 2 weeks later were treated with the pesticides for 6 weeks and then killed; all rats had a partial hepatectomy at week 3. Hepatocarcinogenic potential was assessed by comparing the number and area of glutathione S-transferase placental form positive foci in the liver with those of controls given diethylnitrosamine alone. Positive results were seen with p,p-DDT and triadimefon. Permethrin (mixture of 39% cis form and 61% trans form) showed borderline results. Permethrin (25/75), deltamethrin, cypermethrin (52/48), while trimorphamide and propineb gave negative results. These findings provide experimental evidence to indicate that compounds active in this assay have a potential for liver carcinogenicity in rodents.

[Hakoi K et al; Teratogenesis Carcinog Mutagen 12 (6): 269-76 (1992)]**PEER REVIEWED**

Triadimefon, a triazole fungicide, has been observed to increase locomotion and induce stereotyped behavior in rodents. The present experiments designed to characterize the stereotyped behavior induced by triadimefon used a computer-supported observational method, and tested the hypothesis that these observed effects involved central dopaminergic systems. Adult male and female Sprague Dawley rats were injected with triadimefon (0, 50, 100, and 200 mg/kg) in corn oil (2 ml/kg ip) 4 hr prior to behavioral assessment. The two lowest doses of triadimefon increase the frequency of locomotion and rearing, while the highest dose induced highly stereotyped behaviors, including backward locomotion, circling, and head weaving. Immediately after behavioral testing, the rats were sacrificed, and the striata and olfactory tubercles, terminal fields of the nigrostriatal and mesolimbic dopamine systems, respectively, were removed. Steady-state concentrations of the monoamines dopamine and serotonin and their metabolites were determined by HPLC-EC. In independent experiments, the direct effects of triadimefon on dopamine (D1 and D2) receptor binding and dopamine sensitive adenylate cyclase activity were assessed in vitro using rat striata. Dopamine concentrations were increased in olfactory tubercles, but decreased in striatum. Concentrations of 5-hydroxyindoleacetic acid (the major metabolite of serotonin) were increased only in striatum, and only in animals treated with 200 mg/kg triadimefon. In vitro, triadimefon neither competed with D1 or D2 dopaminergic radioligands nor affected dopamine stimulated adenylate cyclase activity. Together these behavioral and biochemical data lend support to the hypothesis that triadimefon may have actions similar to those produced by indirect-acting dopamine agonists.