November 2012

1 

## REVISED D R A F T

EMERGENCY MEDICAL TREATMENT GUIDE



## CHLOROPICRIN VAPOR EXPOSURE RESULTING

FROM TREATED FIELD VAPOR

______________________________________________________________________________

SYNONYMS: Chloropicrin, Trichloronitromethane, Nit rochloroform, ( Add Label Names )

USE Agricultural pesticide applied for soil treatment

APPEARANCE and PHYSICAL FORM Not visible as airborne vapor. Chloropicrin vapor is heavier than air and can concentrate in low areas during calm or no wind con ditions.

ADVERSE EFFECTS Chloropicrin behaves as a mild sensory irritant at concentrations

between 75 ppb and 150 ppb and is usually detected through odor and

eye sensat ion within 5 minutes of exposure. Lacrimation may occur. At concentrations of about 75 ppb, eye sensation (prickliness or pinching) can be felt in about 20 minutes. At lev els above 150 ppb headache, nausea and vomiting may occur. These symptoms are temporary and reversible following termination of exposure. At levels above 580 ppb for 8 hours or 2000 ppb for 10 minutes, life

- t hreatening effects including pulmonary edema can occur

. Severe pulmonary responses can be dela yed following onset of

exposure. Symptoms of exposure are concentration dependent

. Systemic effects including reproductive o r develo pmental effects are

u nlikely at exposure levels of 150 ppb or lower

.

CLINICAL EFFECTS:

MILD EXPOSURE

- (up to 150 ppb) Mild exposure such as that likely to result from i nhalation and eye contact with low vapo r concentrations , which may move off of a treated field (up to approximately 150 ppb)

 Irritation of eyes, mucous membrane and upper respiratory

tract

 Eye irritation may include lacrimation.

 Cough

 Nausea and headache may develop

 Possible skin irritatio n These signs and symptoms will reverse with termination of exposure but have been reported to persist for up to two days post exposure

.November 2012

2 CLINICAL EFFECTS:

MODERATE EXPOSURE (150ppb to 300 ppb)

 Exposure to airborne concentrations in the range of 150 ppb to 300 ppb or lower but for extended periods can produce the same symptoms as above but with increased severity and may include cough , bronch o spa s m and o ther respiratory symptoms. These signs and symptoms can appear more quickly following elevated exposure s and will reverse with termination of e xposure

. Symptoms have been reported to persist for up to two days post

exposure

.

CLINICA L EFFECTS: SEVERE EXPOSURE (>300 ppb)

 In addition to eye and mucous membrane irritation, systemic symptoms (nausea, vomiting, headache) can occur

 Dyspnea and r espiratory symptoms are likely with increasing exposure concentrations or duration

 Orthostatic hypotension has been reported

 Chest wall pain and rhabdomyolysis have occasionally been reported following industrial inhalation exposures but are unlikely to result from nonoccupational exposure as a result of chloropicrin vapor offgasing from a treate d field

 Delayed pulmonary effects are possible

 Exposures to air concentrations above 500 ppb for 8 hours

or 2000 ppb for 10 minutes can cause life

- threatening pulmonary effects including immediate or delayed edema.

DIFFERENTIAL I n mild exposure symptoms and signs may resemble seasonal DIAGNOSIS or other allergy or viral upper respiratory tract infection.

If breathing difficulties occur or if tracheobronchial tree or pulmonary p a renchyma become involved, signs and symptoms must be differentiated from cardiogenic pulmonary edema, severe viral or bacterial pneumonia, and adult resp iratory distress syndrome.

SPECIAL TESTS Monitoring of patient: Monitor vital signs, CBC and electrolytes after

significant ingestion. Monitor for occult GI hemorrhage (ingestion)

, respiratory distress and increasing pain. Chest radiograph a nd pulse

oxi metry in any patient with respiratory signs or symptoms.November 2012

3 TREATMENT Treatment is symptomatic and supportive. There is no specific antidote for

overexposure to chloropicrin vapor. If eyes are irritated, flush with water. Where instances of direct contact with liquid or undiluted chloropicrin can be ruled out, skin surface decontamination is usually unnecessary. If necessary, remove person to fresh air and provide ventilator support

Bronchospasm: Treat with oxygen, inhaled beta agonists and consider systemic corticosteroids. Injury of globe of eye: Copious irrigation until pH neutral; perform slit lamp exam. Ophthalmology consult. Antibiotics and mydr iatics may be

indicated.

Contact a Regional Poison Control Center at 1

- 800

- 222

- 1222 for clinical

assistance.

REFERENCES

Barry, T., et al. (2010). Community Exposure Following a Drip

- Application of Chloropicrin. J of Agromedicine, 15: 24

- 37.

Goldman, L.R., et al., (1987). Acute Symptoms in Persons Residing Near a Field treated With the Soil Fumigants Methyl Bromide and Chloropicrin. West J Med, July 147: 95

- 98.

Chloropicrin: Hazardous Substances Data Bank (2011). National Library of Medicine , National

Institutes of H ealth and Human Services, Bethesda. http://toxnet.nlm.nih.gov/cgi

- bin/sis/htmlgen?HSDB

TOXICOLOGY BACKGROUND

Undiluted chloropicrin :

Undiluted or concentra ted liquid chloropicrin is highly toxic following ingestion or direct contact with the skin or eyes Inhalation exposure to 4 000 ppb for a few seconds may cause some degree of incapacitation and very brief exposure (a few seconds) to 15 ,000 pp b can cause re spiratory tract injury. Exposure to

concentrations above 15 ,000 ppb if allowed to continue for a minute or longer, can cause pulmonary edema and possibly death

.

Airborne chloropicrin vapor :

Exposure to airborne concentrations of chloropicrin vapor tha t may be present near a field during or immediately after treatment with chloropicrin or a chloropicrin

- containing pesticide is unlikely to produce more than local, transient sensory irritation effects such and eye and upper respiratory irritation.November 2012

4 Human Subject Testing Controlled human subject testing with a study population consisting of young adults, a population more sensitive to sensory irritant effects than the general population including asthmatics and children, show e d that sensory irrita tion as manifest primari l y by eye irritation was the most sensitive indication of chloropicrin exposure. The threshold for ocular irritation in humans was 73 ppb calculated as a BMCL10. T he BMCL10 was derived for a sensitive endpoint and represent ed the lower bound on the response of a small percentage (10%)

of the test population selected to represent the sensitive end of the general population

.

Laboratory Animal Inhalation Studies. Animal s tudies using inhalation exposure have been

conducted with m ale and female CD rats and CD

- 1 mice . The animals were exposed in whole body inhalation chambers to chloropicrin vapor at concentrations of 0, 3 00 , 1 000 or 3 000 pp b for 6 hours per day 5 days per week for 13 weeks. The animals were observed for standar d toxicological parameters during the in

- life phase of the investigation and were subjected to necropsy and extensive histopathological examination following termination. Ocular examination, organ

- body weight ratios were performed and special attention wa s given to respiratory tissues and all lesions. Mortality occurred in 3 of 10 male rats in the high

- dose group during the exposures. Clinical signs of exposure in this group included discoloration in rats and dehydration in mice. Increases in hemoglobin concentration, hematocrit and total erythrocyte count were observed for male mice in all exposure groups. Female mice showed a dose

- related decrease in monocyte count. Increased relative and absolute lung weight was seen in rats and

mice in the mid

- and high

- dose groups. Accompanying these increased weights were microscopic lesions in the lungs and airways consistent with acute and chronic inflammation and nonspecific irritation. These changes included hyperplasia of the respiratory epithelium of the

n asal cavities, goblet cell hyperplasia, bronchial/bronchiolar epithelial hyperplasia and peribronchial fibrosis. The respiratory tissue changes were confined almost entirely to animals

in the mid

- and high

- exposure groups; however, two female mice from th e low exposure group (3 00 pp b ) had evidence of hyalin inclusion in the respiratory tissue. Treatment related changes were not seen in organs or tissue other than the respiratory tract or in the eyes or in hematological, biochemical or urine parameters oth er than those specified above. Subchronic and chronic toxicity studies in three species receiving chloropicrin orally or by inhalation did not produce clinical or histological signs of cardiac effects. Direct cardiac toxicity was not demonstrated in any investigation of chloropicrin toxicity.

Reproductive Function Studies

. Chloropicrin vapor was administered by whole body inhalation for six hours per day, seven days per week to male and female CD rats at concentrations of 0,
500, 1 000 or 1500 ppb throu gh two generations

. The No Observable Adverse Effect (NOAEL) level established for this study was 1 00 ppb for systemic toxicity and greater than 1 500 ppb for developmental toxicity and reproductive parameters. These data indicate that reproduction

fitnes s is not adversely affected by chloropicrin inhalation even at systemically toxic levels.

Developmental Toxicity Studies

. Sexually mature virgin female Sprague

- Dawley rats were impregnated and exposed by whole body inhalation to chloropicrin vapor for 6 hours per day in 16 m3 stainless steel and glass chamber for days 6

- 15 of gestation. Exposure levels were 400

, 12 00 and 3 500 pp b . The animals were observed for survival, appearance, behavior, body weight

. The No Observable Adverse Effect Level (NOAEL) f or maternal toxicity in this studyNovember 2012

5 was 4 00 pp b and 12 00 pp b for fetal toxicity indicating that the developing fetus is not target tissue for chloropicrin. The developmental toxicity of chloropicrin has also been evaluated in a non

- rodent species. Sexual ly mature virgin female New Zealand White SPF rabbits were impregnated and exposed by whole body inhalation to chloropicrin vapor for 6 hours per day in 16 m3 stainless steel and glass chamber for days 7

- 20 of gestation. Exposure levels were 4 00 , 12 00 and 2 000

pp b. The No Observable Adverse Effect Level (NOAEL) for maternal toxicity in this study was

4 00 pp b and 12 00 pp b for fetal toxicity indicating that the developing fetus is not a target tissue for chloropicrin toxicity.

Carcinogenicity Testing

. At le ast six long

- term bioassays have been completed with chloropicrin to evaluate the potential of this compound to cause chronic and/or carcinogenic effects. The bioassays have employed two strains of rats, two strains of mice and Beagle dogs. Lifetime expo sures via whole body inhalation to CD

- 1 mice and CD rats have been reported for chloropicrin

, Chloropicrin has been shown to not cause cancer in animal studies following long

term inhalation

.