National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• 1,3-Dichloropropene (Telone II)
• 1,3-DICHLORO-1-PROPENE
• TELONE II
• 1,3-DCP

Human Toxicity Excerpts

• Seven of 10 volunteers detected 1,3-dichloropropene at an air concn of 3 ppm; some reported fatigue of the sense of smell after few minutes. The same proportion of volunteers detected 1 ppm, but odor was noticeably fainter. ... /It has caused/ edema, redness, & necrosis of skin /from exposure during use/. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 707]**PEER REVIEWED**
  
• Prolonged contact with skin will cause severe burns. [Farm Chemicals Handbook 1989. Willoughby, OH: Meister Publishing Co., 1989., p. C-99]**PEER REVIEWED**
  
• Case reports of hematologic neoplasms following intoxicating exposure to the agricultural chemical 1,3-dichloropropene were examined. In two firefighters, lymphomas appeared simultaneously several years after a simultaneous exposure at the site of a chemical spill. In both, the tumor was refractory to standard regimens of treatment, and the subjects died within a few months of one another. Leukemia developed in a farmer a few months after an initial extended daily exposure during application of the chemical to the soil. The farmer suffered from a smoldering leukemia until after a second series of daily exposures, one year later, when the leukemia became extremely aggressive. Both patterns, immediate and delayed, were recognized in the epidemiology of chemical carcinogenesis. The exposed firefighters did not develop any malignant neoplasms at the time of the report. [Markovitz A, Crosby WH; Arch Int Med 144: 1409-11 (1984)]**PEER REVIEWED**
  
• The effect of a common nematocide soil fumigant mixture on human skin was studied in farmers. The mixture contained 1,3-dichloropropene, 1,2-dichloropropane, and epichlorohydrin. Three cases of skin contact were examined. Patch testing was performed with ingredients of the mixture at 1 percent in acetone (concentration producing no reaction in five volunteers) and with the 20 standard allergens of the International Contact Dermatitis Research Group. Patient 1 received two 1 week exposures 1 year apart and developed an itching erythematous rash. Patient 2 developed the rash after a single exposure. Patient 3 was employed spraying pesticides on a daily basis for 10 years between /the months/ September and January. After 7 years he developed dermatitis on his arms, face, and ears which subsided upon avoidance of the nematocide. Patch testing with 1 percent produced allergic reactions in patient 1 (with spongiosis, lymphocyte infiltration and migration) but not in patients 2 and 3; however, comparisons also showed reaction to a concentration of 10% in acetone after 24 hours and blistering was noted afterward. The /results indicate/ that volunteers, as well as patients 2 and 3, experienced reactions to the mixture as a primary irritant. [Nater JP, Gooskens VHJ; Contact Dermatitis 2 (4): 227-9 (1976)]**PEER REVIEWED**
  
• Forty-six people were treated for exposure to 1,3-dichloropropene fumes following a traffic accident in 1975 involving spillage of 4500 liters of a formulated product. Twenty-four of these, 3 of whom had lost consciousness, were hospitalized overnight with symptoms including headache, irritation of mucous membranes, & chest discomfort. All patients took showers & were given iv fluids & 3 received oxygen & corticosteroids because of chest pain & cough. Eleven of 41 persons tested had slightly higher than average serum SGOT &/or SGPT values, which reverted to normal within 48-72 hr, except for 5 who still had slightly higher then average SGOT values. Follow-up interviews with patients 1-2 wk later revealed symptoms including headache, abdominal and chest discomfort, and malaise. One was diagnosed as having had pneumonia. Symptoms were reported more frequently in those most heavily exposed to the fumes. Patient interviews conducted approx 2 yr after the accident revealed complaints of headache, chest pain or discomfort, & "personality changes" (fatigue, irritability, difficulty in concentrating, or decreased libido). Two had undergone cardiac catheterizations but their arteriograms were normal. There was no correlation of these long-persisting symptoms with intensity of exposure. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 707]**PEER REVIEWED**
  
• AFTER EXPOSURE TO CONCN VAPORS. LACRIMATION IS PROMINENT. ... SEVERE SKIN IRRITATION WITH MARKED INFLAMMATORY RESPONSE OF EPIDERMIS & UNDERLYING TISSUES /FROM DERMAL EXPOSURES/. /DICHLOROPROPENES/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-142]**PEER REVIEWED**
  
• Highly irritating to skin, eyes and all mucous membranes. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 328]**PEER REVIEWED**
  
• A case of sensitization to DD-95 with a nematocide containing approximately 95% 1,3-dichloropropene. A 44 yr old male process operator in a Dutch pesticide manufacturing facility developed an acute bullous dermatitis on the dorsae of both feet. He denied any chemical exposure. Patch testing with an augmented European standard allergen series produced positive reactions to wood tars and thimerosal, which were considered clinically irrelevant. A year later he developed an identical dermatitis. He remembered soiling his shoes with DD-95 the day before. He also recalled soiling his shoes with DD-95 before the earlier incident. He was patch tested with DD-95 at concn of 0.005, 0.03, 0.1, 0.5, 1, and 2% in petrolatum. All concn produced a positive response after 2 and 3 days. Patch testing 20 volunteers with 0.05% DD-95 produced negative results. It was concluded that the patient was probably sensitized to DD-95 after the initial exposure. Since DD-95 is toxic and a potent sensitizer, farmers and operators employed at pesticide manufacturing facilities who develop dermatoses should be patch tested with DD-95 as well as standard allergen series. [Bousema MT et al; Contact Dermatitis 24 (2): 132-3 (1991)]**PEER REVIEWED**
  
• The effects of subchronic exposure to 1,3-dichloropropane on liver and kidney function in employees of the Dutch flower bulb industry were examined. The study was part of a larger environmental and biological monitoring study of 1,3-dichloropropene in the Dutch flower bulb culture industry. The cohort consisted of 14 commercial applicators who used 1,3-dichloropropene in soil fumigation operations in the Bollenstreek region of the Netherlands. Venous blood and spot urine samples were collected from the subjects at the start of the bulb culture season in July and after the season ended in October. The effects on liver function were assessed by determining serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase, and total bilirubin. The effects on kidney function were evaluated by measuring serum beta2-microglobulin and creatinine and urinary albumin, retinol binding protein), beta-galactosidase, and alanine aminopeptidase. Blood glutathione concn and erythrocyte glutathione-S-transferase activity were determined to evaluate the effect on blood glutathione conjugation capacity. Data from the environmental monitoring study indicated that the fumigators were exposed to time weighted average 1,3-dichloropropene concn of 1.9 to 18.9 mg/cu m, which exceeded the Dutch standard of 5 mg/cu m 30% of the time. A decrease in serum total bilirubin concn was the only parameter of liver function to be significantly affected by 1,3-dichloropropene. Urine albumin and retinol binding protein concn were significantly increased and serum creatinine concn was significantly decreased during the spraying season. Blood glutathione concn and erythrocyte glutathione-S-transferase activity were significantly decreased by 1,3-dichloropropene over the spraying season. The authors suggest that exposure to 1,3-dichloropropene over a spraying season may induce a subclinical nephrotoxic effect. The decreases in glutathione and glutathione-S-transferase values indicate that 1,3-dichloropropene affects glutathione conjugating capacity. [Brouwer EJ et al; Br J Ind Med 48 (3): 167-72 (1991)]**PEER REVIEWED**
  
• 1,3-D is metabolized by conjugation with glutathione & is excreted primarily as a mercapturic acid conjugate. This urinary metabolite has been detected in workers exposed to 1,3-D vapor during fumigation. Applicator exposure was studied using personal air monitoring of 1,3-D, & monitoring of urinary excretion of the mercapturic acid metabolite & the excretion of the renal tubular enzyme, N-acetyl glucosaminidase (NAG). Urinary excretion of the metabolite correlated well with exposure to 1,3-D. Four workers ( out of 15 studied) had clinically elevated activity of NAG in any of their urine collections after baseline. Nine workers showed >25% increases in NAG excretion when compared to baseline. Dichloropropene air exposure products of >700 mg min/cu m or excretion of the metabolite >1.5 mg/day distinguished abnormally high daily excretion of NAG. These data demonstrate a relationship between air exposure & dose, & a possible subclinical nephrotoxic effect in workers handling 1,3-D. [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1058]**PEER REVIEWED**
  
• A 27 year old previously healthy male worker who accidentally drank a solution containing 1,3-dichloropropene (mixture of cis- and trans-isomers) developed gastrointestinal distress, adult respiratory distress syndrome, hematological and hepatorenal functional impairment, and died 40 hours after ingestion. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 936 (1999)]**PEER REVIEWED**
  
• Symptomatology: 1A) Inhalation, high vapor concn: gasping, refusal to breathe, coughing, substernal pain, & extreme respiratory distress at vapor concn over 1500 ppm. Irritation of eyes & upper respiratory mucosa appears promptly after exposure to concentrated vapors. Lacrimation & headache are prominent. Coma may occur rapidly. B) Inhalation, low vapor concn: central nervous depression & moderate irritation of respiratory system. Headache is frequent. 2) Dermal: severe skin irritation with marked inflammatory response of epidermis & underlying tissues. 3) Oral: acute gastrointestinal distress with pulmonary congestion & edema. Central nervous depression, perhaps even in the absence of impaired oxygen uptake. 4) By any route, possible late injuries to liver, kidneys & heart. 5) After inhalation exposures, malaise, headache, chest & abdominal discomfort & irritability have been reported to persist for several weeks & perhaps for several years. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-142]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• WHEN FED TO RATS IN SINGLE DOSES AS 2.5% SOLN IN CORN OIL ... LIVER APPEARED TO BE PRINCIPAL SITE OF INJURY. DOSES OF 0.5 G/KG AS A 25% SOLUTION IN PROPYLENE GLYCOL WERE LETHAL TO RABBITS WHEN APPLIED TO SKIN BENEATH CUFF FOR 24 HR. DEATH FROM INHALATION WAS USUALLY ASSOC WITH SEVERE LUNG INJURY. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-168]**PEER REVIEWED**
  
• When fed by gavage to groups of rats at 0, 1, 3, 10, or 30 mg/kg body wt, 6 days/wk for 13 wk it was concluded ... /that/ 3 to 10 mg/kg was a nontoxic effect level. ... The relative wt of kidneys ... were incr at 30 mg/kg/day in both sexes & in males at 10 mg/kg/day. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 4228]**PEER REVIEWED**
  
• WHEN 1,3-DICHLOROPROPENE INSTILLED INTO EYES OF RABBITS & THEN WASHED FROM ONE EYE BY STREAM OF FLOWING TAP WATER, SEVERE CONJUNCTIVAL IRRITATION WAS SEEN IN 4 OF 6 RABBITS & SLIGHT TO MODERATE CORNEAL INJURY WAS SEEN IN 2 OF THEM WITHIN 24 HR. INJURY GRADUALLY HEALED BY 8TH DAY. IN MOST INSTANCES, WASHING WITH WATER WAS EFFECTIVE IN AVERTING INJURY. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 162]**PEER REVIEWED**
  
• BRIEF EXPOSURE TO CONCN ABOVE 2700 PPM WERE IRRITATING TO EYES & NOSE OF RATS & CAUSED SEVERE LUNG, NASAL, LIVER, & KIDNEY INJURY. RATS WERE KILLED BY 2 HR of EXPOSURE TO 1000 PPM, BUT OTHERS SURVIVED 1 HR OF SUCH EXPOSURE. A PECULIAR GARLICKY ODOR WAS NOTED ON ... /THOSE/ EXPOSED TO 700 PPM OR GREATER. SINGLE EXPOSURE OF 7 HR TO 400 PPM WAS LETHAL TO GUINEA PIGS & SEVERELY INJURIOUS TO RATS. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 162]**PEER REVIEWED**
  
• EXPOSURE OF RATS & GUINEA PIGS TO VAPOR CONCN OF ... 50 OR 11 PPM, 7 HOURS/DAY, 5 DAYS/WEEK FOR 1 MONTH PRODUCED LIVER & KIDNEY INJURY. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 162]**PEER REVIEWED**
  
• MALE RATS EXPOSED TO MIXED ISOMERS OF 1,3-DICHLOROPROPENE AT CONCN OF 3 PPM FOR 7 HR/DAY, 5 DAYS/WK FOR 6 MO SHOWED SLIGHT, REVERSIBLE CHANGE IN KIDNEYS. NO CHANGE WAS DETECTED IN RATS KILLED 3 MO AFTER LAST EXPOSURE. FEMALE RATS, MALE & FEMALE RABBITS, MALE & FEMALE GUINEA PIGS, & FEMALE DOGS SHOWED NO ADVERSE EFFECT ... AT 1 PPM (4.5 MG/CU M). [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 162]**PEER REVIEWED**
  
• Necrosis & edema occurred when liquid 1,3-dichloropropene was confined on skin of rabbits but if allowed to evaporate the effect was greatly reduced. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 4226-7]**PEER REVIEWED**
  
• Subchronic inhalation toxicity data on 1,3-dichloropropene are contradictory. Older data indicate commercial product studied ... (1958-1975) was quite irritating & hepatotoxic, but data developed on currently produced fumigants indicate considerably less hepatotoxicity. ... In early subacute study ... considerable liver & kidney injury /were/ evident grossly in small groups of rats exposed 19 times to 50 ppm, 7 hr/day in a 28-day period. Studies with more recently produced product, Telone II soil fumigants (47% cis, 45% trans, the balance related cmpd), indicate considerably lower toxicity /in/ Fischer 344 rats & CD-1 mice ... exposed 7 hr/day, 5 days/wk for 13 wk to 0, 93, 32, or 12 ppm. Exposures resulted only in failure to gain wt (high dose rats & female mice) & focal histomorphological changes of epithelium of nasal septums & turbinates in high dose rats of both sexes as well as female rats exposed to 32 ppm. Female, but not male mice, exposed to 93 ppm showed similar effects. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 4226]**PEER REVIEWED**
  
• THE TOXICITY OF MIXED ISOMERS OF 1,3-DICHLOROPROPENE, WHEN REPEATEDLY INHALED AT LOW CONCN (1 OR 3 PPM) FOR SIX MO WAS INVESTIGATED. RATS, GUINEA PIGS, RABBITS, & DOGS RECEIVED 7 HR DAILY EXPOSURES 5 DAYS PER WK TO 1 PPM FOR 6 MO WITH NO ADVERSE EFFECT. THE ONLY EFFECT IN ANY GROUP EXPOSED TO 3 PPM WAS SLIGHT, APPARENTLY REVERSIBLE CHANGE SEEN MICROSCOPICALLY IN KIDNEYS OF MALE RATS EXPOSED 7 OR 4 HR/DAY. [TORKELSON TR, OYEN F; AMER IND HYG ASSOC J 38 (5): 217-23 (1977)]**PEER REVIEWED**
  
• In a test conducted on a mixed assemblage of emerald shiners & fathead minnows exposed to 1,3-dichloropropene, 100% of the fish survived 3 days at 1,000 ug/l, & none survived at 10,000 ug/l. [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.B-4 (1980)]**PEER REVIEWED**
  
• Four preparations of 1,3-dichloropropene were assayed for mutagenic activity before and after silicic acid chromatography. None of the preparations retained mutagenic activity after chromatography, but each contained direct acting mutagenic polar impurities in the Ames test. The specific mutagenic activities of the unpurified samples appeared to be detected by the mutagenic activities of their polar impurities. A mixture of mutagenic polar impurities could be regenerated by refluxing a purified preparation for 6 hr. The fraction of polar impurities from one of the preparations was analyzed by GC/MS. Although its composition was too complex to characterize completely, two known mutagens, epichlorhydrin and 1,3-dichloro-2,2-propanol, were tentatively identified. [Talcott RE, King J; J Natl Cancer Inst 72 (5): 1113-6 (1984)]**PEER REVIEWED**
  
• Telone was tested over a range of 7 doses in the mouse to assess their testicular toxicity. Measures of potential toxicity were sperm morphology, sperm counts and morphology testicular weights. Each pesticide was injected intraperitoneally in a single dose on each of 5 days. Testicular toxicity was assessed at 35 days. None of the pesticides tested, including the known human male testicular toxin, DBCP, produced statistically significant differences in the parameters from vehicle injected controls. [Osterloh J et al; Mutat Res 116 (3-4): 407-15 (1983)]**PEER REVIEWED**
  
• 1,3-Dichloropropene at 20 ug/ml of air, killed 100% of microsclerotia after incubation for 30 hr, and at 100 ug/g of soil moisture after incubation for 3 days. Higher temperatures increased the toxicity. [Ben Yephet Y et al; Pestic Sci 12 (2): 170-4 (1981)]**PEER REVIEWED**
  
• Telone II (technical grade 1,3-dichloropropene) was evaluated in chronic toxicology/carcinogenicity studies using Fischer-344 rats and B6C3F1 mice of both sexes. Doses administered were 0, 25, or 50 mg/kg to rats (52 rats of each sex per dose group) and 0, 50, or 100 mg/kg to mice (50 mice of each sex per dose group). Telone II was given in corn oil by gavage 3 times per week for 104 weeks. Ancillary studies were conducted in which 5 rats of each sex in each dose group were killed and necroscopied after 9, 16, 21, 24, or 27 months. There was a significant increase (0.001
• 1,3-Dichloropropene (DCP) was evaluated for the induction of sex-linked recessive lethal mutations in Drosophila melanogaster using a standard protocol approved by the National Toxicology Program. Canton-S wild-type males were treated with concentrations of 1,3-dichloropropene that result in approximately 30% mortality. Following treatment, males were mated individually to 3 harems of Basc virgin females to produce 3 broods for analysis. 1,3-Dichloropropene was positive at a dose of 5,570 ppm when administered to males by feeding. [Valencia R et al; Environ Mutagen 7: 325-48 (1985)]**PEER REVIEWED**
  
• 1,3-Dichloropropene (DCP), which has found widespread use as a soil fumigant, was evaluated for its potential effects on embryonal and fetal development in rats and rabbits. Pregnant Fischer 344 rats and New Zealand White rabbits were exposed to 0, 20, 60, or 120 ppm of 1,3-dichloropropene for 6 hr/day during gestation days 6-15 (rats) or 6-18 (rabbits). Exposure-related decreases in maternal weight gain and feed consumption were observed in rats at all treatment levels. Decreased weight gain was also observed among rabbits at 60 and 120 ppm. A slight, but statistically significant, increase in the incidence of delayed ossification of the vertebral centra in rats exposed in utero to 120 ppm of 1,3-dichloropropene was considered of little toxicologic significance in light of the maternal toxicity observed at this exposure concentration. No evidence of a teratogenic or embryotoxic response was observed in either species at any exposure level /up to 120 ppm/ tested. [Hanley TR et al; Funda Appl Toxicol 8 (4): 562-70 (1987)]**PEER REVIEWED**
  
• ... 1,3-Dichloropropene administered by intraperitoneal injections of 0 to 75 mg/kg/day for 5 days had no effect on sperm count, sperm morphology, or testicular weights in mice. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 337]**PEER REVIEWED**
  
• The effects of 1,3-Dichloropropene (DCP) upon the trypsin, trypsin inhibitor, amylase, & lipase activities in the blood serum of albino rats /were investigated/. Animals were fed daily doses of 0.1, 0.5, & 2.5 mg of 1,3-dichloropropene/kg bw for 6 months. The results showed that ... trypsin activity increased through the 6 months of admin, while the activity of trypsin inhibitor decreased after the second month of admin. Also blood lipase activity permanently increased, while amylase tended to be reduced. [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.C-19-20 (1980)]**PEER REVIEWED**
  
• Not toxic to bees when used as directed. [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994., p. 309]**PEER REVIEWED**
  
• Groups of albino rats were fed daily oral doses of 2.2 & 55 mg of 1,3-dichloropropene (DCP)/kg /body weight/ for 30 days. The results showed that by day 30 of admin the excretory liver function was altered, as evidenced by pigment circulation in the blood, raised thymol test values, cholesterol level, & the stimulated increase of fructose 1-monophosphate aldolase. [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.C-20 (1980)]**PEER REVIEWED**
  
• An oral dose of 3500 mg/kg /in dogs/ caused staggering, partial /CNS depression/ & death within 24 hr. [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.C-12 (1980)]**PEER REVIEWED**
  
• Rats were exposed to 3 ppm (13.6 mg/cu m) for periods of 0.5, 1, 2, or 4 hr/day, 5 day/wk for 6 mo. Only the rats exposed for 4 hr/day showed ... cloudy swelling of the tubular epithelium. [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.C-18, C-19 (1980)]**PEER REVIEWED**
  
• ... The acute toxicity /of 1,3-dichloropropene/ to saltwater aquatic life occurs at concn as low as 790 mg/l. [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.B-6 (1980)]**PEER REVIEWED**
  
• The effectiveness of 1,3-dichloropropene applied at various rates and horizontal chisel spacing was evaluated for control of cotton (Gossypium) root rot caused by Phymatotrichum omnivorum. With 281 l/ha applied in 48 cm horizontal chisel spacing, cotton lint yield was 724 kg/ha, as compared with 250 kg/ha for the check. The fumigant treatments delayed infection by the fungus and reduced the number of infected plants as compared with the check. A 2 wk delay in plant mortality is sufficient for the short-season cultivars to set and mature a near-normal crop. [Heilman MD et al; Plant Dis Rep 62 (7): 609-12 (1978)]**PEER REVIEWED**
  
• The subchronic reproductive toxicity of DD, a mixture of 1,3-dichloropropene and 1,2-dichloropropane, was studied in rats. Wistar rats were exposed by inhalation to 0, 10, 30, or 90 ppm DD 6 hr daily 5 days a wk for 10 wk. Selected male rats from each exposure group were mated with unexposed virgin females during wk 3, 5, 8, and 10 of exposure. On the 12th day after mating, each female was killed and examined for numbers of corpora lutea, uterine implantation, and resorption sites. After the 10 wk exposure period, selected females from each exposure group were mated with unexposed males. Gestation lengths were recorded. After delivery, the number of live and dead pups was recorded on postnatal days 0, 1, and 4. The litters were weighed on postnatal days one and four. Other animals were killed 10 to 22 hr, 5 wk, or 7 wk after exposure ended and necropsied. Semen samples were examined for sperm abnormalities. Vaginal smears were taken and stained to evaluate estrus cycle activity. DD exerted no adverse effects on sperm morphology or estrus cycling activity. None of the measured reproductive parameters were affected by DD. Kidney and liver weights were slightly increased in rats of either sex exposed to 90 ppm DD. No other treatment related gross or histopathologic changes were seen. /DD/ [Linnett SL et al; Fundam and Appl Toxicol 10 (2): 214-23 (1988)]**PEER REVIEWED**
  
• Toxicology and carcinogenesis studies of Telone II (a soil fumigant containing approx 89% cis- and trans-1,3-dichloropropene, 2.5% 1,2-dichloropropane, 1.5% of a trichloropropene isomer, and 1.0% epichlorohydrin) were conducted by administering the commercial-grade formulation in corn oil by gavage to groups of 52 male and 52 female F344/N rats at doses of 0, 25, or 50 mg/kg and to groups of 50 male and 50 female B6C3F1 mice at doses of 0, 25, or 50, 100 mg/kg. Doses were administered three times per week for 104 weeks. Ancillary studies were conducted in which dose groups containing five male and five female rats were killed after receiving Telone II for 9, 16, 21, 24, or 27 months. The primary organs affected were the forestomach (rats and mice), urinary bladder (mice), lung (mice), and liver (rats). Compound related non-neoplastic lesions included basal cell or epithelial hyperplasia of the forestomach (rats and mice), epithelial hyperplasia of the urinary bladder (mice), and kidney hydronephrosis (mice). Neoplastic lesions associated with administration of Telone II included squamous cell papillomas of the forestomach, squamous cell carcinoma of the forestomach, transitional cell carcinoma of the urinary bladder, alveolar/bronchiolar adenomas, and neoplastic nodules of the liver. Development of lesions in the forestomach (basal cell hyperplasia and squamous cell papilloma) was observed to be time dependent. The results of the scheduled kills supported the findings of the carcinogenesis studies. /Telone II (Technical grade 1,3-Dichloropropene, containing 1.0% epichlorohydrin as a stabilizer)/ [DHHS/NTP; Toxicology and Carcinogenesis Studies of Telone II (Technical Grade 1,3-Dichloropropene Containing 1.0% Epichlorhydrin as a Stabilizer) in F344/N Rats & B6C3F1 Mice (Gavage Studies) p. 9 (1985) Technical Rpt Series No. 269 NIH Pub No. 85-2525]**PEER REVIEWED**
  
• Adult Fischer 344-rats and New-Zealand-White rabbits were used to determine the effect of the inhalation of 1,3-dichloropropene in concn ranging from 20 to 120 ppm. The rats were exposed to 1,3-dichloropropene from gestation days six to 15, while the rabbits were exposed to the product from gestation days six to 18. At all dose levels, reduction in maternal body weight and decreased feed consumption were evident. Rats exposed in-utero to 120 ppm 1,3-dichloropropene had a slight but significant increase in the incidince of delayed ossification of the vertebral centra, but there was no consistent evidence of teratogenic or embryotoxic effects in either species, regardless of the dose. The appearance and behavior of the exposed animals were not altered, and there was no mortality attributable to treatment. [Hanley TR Jr et al; Fundam and Appl Toxicol 8 (4): 562-70 (1987)]**PEER REVIEWED**
  
• The reproductive and developmental effects of inhaled 1,3-dichloropropene were studied using Fischer 344 rats. The F0 generation animals were exposed by inhalation to 0, 10, 30, or 90 ppm 1,3-dichloropropene for 6 hr/day, 5 days/wk for 10 wk before mating and for 6 hr/day, 7 days/wk during mating, gestation, and lactation. Weaned F1 rats followed the same dosing regimen. The animals were evaluated for fertility, pup survival, length of gestation, litter size, pup body wt, pup sex ratio, gross pathology, and histological alterations. 1,3-dichloropropene exposure had no significant effect on either behavior or clinical appearance of the animals. A decrease in body wt during the exposure period was observed for all F0 and F1 males and females treated at the 90 ppm level. No significant changes in mating, conception, gestation period, cohabitation time required for mating, pup survival, pup body wt, litter size, or pup appearance were determined following 1,3-dichloropropene treatment, nor were any treatment related histopathological changes observed in male or female reproductive tissues. The exposure of adult male an female rats to 90 ppm 1,3-dichloropropene produced characteristic stress lesions in the nasal mucosa. The authors conclude that the inhalation of 1,3-dichloropropene vapors does not adversely affect the reproduction and neonatal development in Fischer 344 rats. [Breslin WJ et al; Fund Appl Toxicol 12 (1): 129-43 (1989)]**PEER REVIEWED**
  
• A series of mutation experiments was carried out with Drosophila melanogaster using inhalation exposure. 1,2-Dichloroethane and 1,2-dibromoethane were active in the sex-linked recessive lethal assay, whereas dichloromethane, dibromomethane, 1,2-dichloropropane an 1,3-dichloropropane were not. Compared to 1,2-dibromoethane, 1,2-dichloroethane is a less potent mutagen in the sex-linked recessive lethal assay system. For both compounds, there is no evidence of a clear-cut dose-rate effect. 1,2-Dichloroethane and dichloromethane were also investigated in the somatic mutation and recombination test, with results similar to those from the sex-linked recessive lethal assay. For 1,2-dichloroethane the genetic activity profile was further analyzed by carrying out a sex-chromosome loss assay and a complementation analysis of a series of induced recessive lethal mutations. A review of the use of inhalation in mutagenicity assays with Drosophila shows that this route of exposure is an effective one. Especially with chronic exposure times, rather low exposure concn can be detected. With compounds of intermediate volatility inhalation is not superior to other modes of administration; nor is it likely to be sensitive enough for in situ monitoring. [Kramers PG et al; Mutat Res 252 (1): 17-33 (1991)]**PEER REVIEWED**
  
• The subchronic reproductive toxicity of D-D, a mixture of 1,3-dichloropropene and 1,2-dichloropropane, was studied in rats. Wistar rats were exposed by inhalation to 0, 10, 30, or 90 ppm 1,3-dichloropropene/1,2-dichloropropane 6 hr daily 5 days a wk for 10 wk. Selected male rats from each exposure group were mated with unexposed virgin females during wk 3, 5, 8, and 10 of exposure. On the 12th day after mating, each female was killed and examined for numbers of corpora lutea, uterine implantation, and resorption sites. After the 10 wk exposure period, selected females from each exposure group were mated with unexposed males. Gestation lengths were recorded. After delivery, the number of live and dead pups was recorded on postnatal days 0, 1, and 4. The litters were weighed on postnatal days one and four. Other animals were killed 10 to 22 hr, 5 wk, or 7 wk after exposure ended and necropsied. Semen samples were examined for sperm abnormalities. Vaginal smears were taken and stained to evaluate estrus cycle activity. 1,3-Dichloropropene/1,2-dichloropropane exerted no adverse effects on sperm morphology or estrus cycling activity. None of the measured reproductive parameters were affected by 1,3-dichloropropene/1,2-dichloropropane. Kidney and liver wt were slightly increased in rats of either sex exposed to 90 ppm 1,3-dichloropropene/1,2-dichloropropane. No other treatment related gross or histopathologic changes were seen. It was concluded that subchronic inhalation of 1,3-dichloropropene/1,2-dichloropropane at concn up to 90 ppm does not affect the reproductive system of rats of either sex. [Linnett SL et al; Fund Appl Toxicol 10 (2): 214-23 (1988)]**PEER REVIEWED**
  
• A comprehensive chronic inhalation toxicity & oncogenicity bioassay was performed on rats treated with 1,3-dichloropropene. 1,3-Dichloropropene was used as an agricultural pesticide & inhalation was thought to be the major route of human exposure. Male & female Fischer 344 rats & B6C3F1 mice were exposed to 1,3-dichloropropene by inhalation for 6 hr/day, 5 days/wk for up to 24 mo. Concn of 0, 5, 20, & 60 ppm 1,3-dichloropropene vapors were used. No clinical signs indicative of toxicity & no significant differences in survival were observed between any groups of either sex of rats or mice. There were no apparent increases in palpable masses due to exposure to 1,3-dichloropropene. Data from urinalysis & hematological & biochemical studies of 1,3-dichloropropene treated animals showed no signs of toxicity. Gross pathological exam of treated rats revealed no apparent exposure related effects. In mice, morphological alterations involving the urinary bladder & lung were attributed to 1,3-dichloropropene exposure. Hyperplasia of the transitional epithelium of the urinary bladder was observed in nearly all female mice exposed to 60 ppm 1,3-dichloropropene for 12 & 24 mo & in some female mice exposed to 20 ppm for 12 & 24 mo. An incr in benign bronchioloalveolar adenomas was seen in male mice exposed to 60 ppm 1,3-dichloropropene. There were no statistically significant increases in primary, benign, or malignant tumor incidence in exposed rats. Nasal tissue of mice exposed to 20 or 60 ppm & of rats exposed to 60 ppm for 24 mo showed morphological alterations consisting mainly of hypertrophy & hyperplasia. It was concluded that the results clearly demonstrate a dramatic difference between the tumorigenic response of rats & mice to inhaled 1,3-dichloropropene versus that observed in a previous gavage bioassay & state that this finding is significant because most human exposure is by inhalation of vapor & not by ingestion. [Lomax LG et al; Fund Appl Toxicol 12 (3): 418-31 (1989)]**PEER REVIEWED**
  
• The role of the chlorinated alkane solvent effect on the inhibition of hepatic triglyceride secretion was investigated using male Swiss Webster mice and male Sprague Dawley rats. Triglycerides were measured in serum of treated animals or in supernatants of isolated hepatocytes exposed to solvents and tritiated glycerol. Two hours following carbon tetrachloride injection, triglyceride levels were reduced significantly to 42% o control values and to 15% by 8 hr. Methylene chloride caused a more rapid decline in serum triglyceride concn. Significant dose related decreases in serum triglyceride levels at 2 hr followed the administration of 1-chloropropane, 1-chlorobutane, 1-chloropentane, 1-chlorohexane, 1,2-dichloroethane, 1,3-dichloropropane, 1,4-dichlorobutane, and 1,5-dichloropentane. The shorter chain, less lipid soluble solvents were the more potent at decreasing triglyceride secretion in vivo. In freshly prepared isolated hepatocyte systems, the relationship between 50% inhibitory concn and lipid solubility was opposite to that observed in vivo. The more lipid soluble solvents were the more potent at decreasing secretion in vitro. The authors suggest from this finding that nonspecific solvent effects on membrane integrity may be important in the inhibition of triglyceride secretion. The chlorinated alkane induced development of fatty liver through inhibition of triglyceride secretion may be related to lipid solubility of the chemical rather than to its metabolism to free radicals. [Selan FM, Evans MA; Res Comm Chem Pathol Pharmacol 55 (2): 249-68 (1987)]**PEER REVIEWED**
  
• A comprehensive study was made of the subchronic toxicity of inhaled technical grade 1,3-dichloropropene in rats & mice. Fischer 344 rats & B6C3F1 mice were exposed to target concn of 0, 10, 30, 90, & 150 ppm 1,3-dichloropropene for 6 hr/day, 5 days/wk, for 13 wk. Animals were observed for signs of toxicity twice daily on exposure days & were weighed approx weekly. After exposure, surviving animals were sacrificed & examined by clinical laboratory, gross necroscopic, & histopathologic studies. No treatment related deaths were observed. Dose related decreases in body wt were seen in both species. No significant treatment related changes in clinical chemistry, hematology, & urinalysis profiles were noted, except those which could be related to reduced growth. Both sexes of rats & mice showed treatment related histological changes in nasal mucosa. Female mice had urinary bladder alterations & female rats had uterine changes. Dose related slight degeneration of nasal olfactory epithelium &/or mild nasal respiratory epithelial hyperplasia were observed in all animals exposed to the 2 highest doses & in 2 of 10 male rats exposed to 30 ppm. High exposure group mice showed some focal areas of respiratory metaplasia. Uterine changes in rats were suggestive of hypoplasia & were attributed to growth retardation. Female mice in the 2 highest exposure groups had diffuse moderate hyperplasia of the urinary bladder transitional epithelium. The authors conclude that nasal mucosa of rats & mice & urinary bladder of female mice are potential target tissues of inhaled 1,3-dichloropropene. [Stott WT et al; Fund Appl Toxicol 11 (2): 207-220 (1988)]**PEER REVIEWED**
  
• Adult Fischer 344 rats & New Zealand White rabbits were used to determine the effect of the inhalation of 1,3-dichloropropene in concns ranging from 20-120 ppm. The rats were exposed to 1,3-dichloropropene from gestation days 6-15, while the rabbits were exposed to the product from gestation days 6-18. At all dose levels, reduction in maternal body wt & decreased feed consumption were evident. Rats exposed in utero to 120 ppm 1,3-dichloropropene had a slight but significant incr in the incidence of delayed ossification of the vertebral centra, but there was no consistent evidence of teratogenic or embryotoxic effects in either species, regardless of the dose. The appearance & behavior of the exposed animals were not altered, & there was no mortality attributable to treatment. It was concluded that exposure of pregnant rats & rabbits to 1,3-dichloropropene in concns of up to 120 ppm during the embryonic period does not present a teratogenic risk for either species, & that the slight fetal toxicity observed is seen at a 1,3-dichloropropene level which also induces evident maternal toxicity. [Goldsmith JR; Arch Environ Health 43 (4): 1988 316-7 (1988)]**PEER REVIEWED**
  
• Subchronic studies were also performed with rats, rabbits, & guinea pigs, involving exposures to 1 or 3 ppm for 125-130 times over a period of 185 days. Male rats exposed to 3 ppm exhibited cloudy swelling of the renal tubular epithelium. Female rats exhibited slight but statistically significant increases liver-to-body weight ratio. [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1058]**PEER REVIEWED**
  
• F344 rats of each sex were gavaged with Telone in corn oil at doses of 0, 25, & 50 mg/kg/day 3 times/wk. No incr mortality occurred in treated animals. Elevated incidence of the following tumors were observed at the highest dose tested: (a) forestomach squamous cell papillomas in males & females; (b) forestomach squamous cell papillomas & carcinomas combined in males & (c) liver neoplastic nodules in males. The incr incidence of forestomach tumors was accompanied by a positive trend for forestomach basal cell hyperplasia in male & female rats of both treated groups (25 & 50 mg/kg/day). B6C3F1 mice of each sex were gavaged with Telon II in corn oil at doses of 0, 50, & 100 mg/kg/day 3 times/wk for 104 wk. A total of 50 mice/sex were used for each dose group. Due to excessive mortality in control male mice from myocardial inflammation approx 1 yr after the initiation of the study (a time when neoplastic lesions would not be expected to occur), conclusions pertaining to oncogenicity were based on both concurrent control data as well as on available NTP historical control data. Elevated incidence of the following tumors were observed either at the highest dose level tested or at both dose levels tested: (a) forestomach squamous cell papillomas or papillomas & carcinomas combined in males & females, & squamous cell carcinomas in females; (b) urinary bladder transitional cell carcinomas in males & females; & (c) lung adenomas, & adenomas & carcinomas combined in males & females. [Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1058]**PEER REVIEWED**
  
• During /acute inhalation/ exposure & observation periods, the following symptoms were observed: partial closing of the eyes, pilo-erection, salivation, lacrimation, lethargy, diarrhea, reduction in respiratory rate, irregular respiratory movements (lung congestion was observed in dead animals) & hunched posture, brown staining of fur & fur loss, & reddening of ears, tail, & feet. Pathological signs were cardiopulmonary failure, acute tubular necrosis in the kidneys, & local effects on the respiratory tract. [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.75 (1993)]**PEER REVIEWED**
  
• The following signs of toxicity were observed after oral admin: hunched posture, lethargy, pilo-erection, decreased respiratory rate, ptosis, diarrhea, diuresis, ataxia, tip-toe gait, red/brown staining around the snout, tremors, emaciation, & pallor of the extremities. Hemorrhages & congestion were found in the lungs & GI tract. The livers showed patchy areas of pallor. [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.75 (1993)]**PEER REVIEWED**
  
• After dermal application, the signs of intoxication were: diarrhea, lethargy, hunched posture, decreased respiratory rate, with lacrimation, salivation, ataxia or abasia, loss of righting reflex, diuresis, & red/brown staining around the eyes, snout, or mouth. The lungs & GI tract showed hemorrhages & irritation. Signs of skin irritation manifested by edema, eschar formation, or subcutaneous hemorrhage were apparent. [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.78 (1993)]**PEER REVIEWED**
  
• Technical grade 1,3-dichloropropene (containing 1.0% epichlorohydrin) was tested for carcinogenicity by gavage in one experiment in mice and in one experiment in rats. In mice, it produced dose related increases in the incidence of benign and/or malignant tumors of the urinary bladder, lung and forestomach. In male rats, it produced dose-related increases in the incidence of benign and malignant tumors of the forestomach. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 934 (1999)]**PEER REVIEWED**
  
• Treatment.with buthionine sulfoximine (0.2 m in 0.58% NaCl, 4 ml/kg body weight (to inhibit glutathione synthesis) 4 hr before dosing. with 1,3-dichloropropene or with diethyl maleate (3.1 m in corn oil, 0.4 ml/kg body weight) (to deplete glutathione) or corn oil itself 1 hour before dosing with 1,3-dichloropropene at 50 and 75 mg/kg body weight, resulted in elevations of N-acetylglucosaminidase excretion. In contrast, treatment with aminooxyacetic acid (0.125 m in 0.85 % NaCl, 4 ml/kg body weight) (which inhibits beta lyase activity) 1 hour before 1,3-dichloropropene injection prevented the 1,3-dichloropropene induced release of N-acetylglucosaminidase from the renal tubule. These results suggest that the nephrotoxic effects of 1,3-dichloropropene may be mediated through the mercapturic acid metabolites in the kidney, rather than glutathione depletion. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 937 (1999)]**PEER REVIEWED**
  
• 1,3-Dichloropropene was administered to male and female Fischer 344 rats and B6C3F1 mice for 13 weeks (0, 5, 15, 50 or 100 mg/kg bw per to rats or 0, 15, 50, 100 or 175 mg/kg bw per day to mice) in the diet by mixing a microencapsulated formulation of 1,3-dichloropropene into animal feed (microencapsulated in a 80/20% starch) sucrose matrix; 1,3-dichloropropene consisted of 50.7% cis, 45.1% trans isomers). There was a decrease in the body weights of male and female rats ingesting more than 5 and 15 mg/kg bw per day, respectively, and a decrease in body weights of mice in all treatment groups relative to controls. A low degree of basal cell hyperplasia in the nonglandular portion of the stomach of male and female rats exposed to more than 15 mg/kg bw per day was also observed, but the severity of the damage was somewhat diminished after a four week recovery period during which the rats were not exposed to 1,3-dichloropropene. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 937 (1999)]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LD50 Rat oral 140 + or - 25 mg/kg [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.C-11 (1980)]**PEER REVIEWED**
  
• LD50 Mouse oral 300 + or - 27 mg/kg [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.C-11 (1980)]**PEER REVIEWED**
  
• LD50 Rabbit dermal 2100 + or - 260 mg/kg [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.C-11 (1980)]**PEER REVIEWED**
  
• LD50 Rabbit dermal 504 mg/kg [Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 485]**PEER REVIEWED**
  
• LC50 Rat inhalation 2.7-3.07 mg/l air/4 hr [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994., p. 308]**PEER REVIEWED**
  
• LD50 Rat percutaneous 1200 mg/kg [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994., p. 308]**PEER REVIEWED**
  
• LD50 Rat (male) oral 713 mg/kg /a 92% product (a cis:trans mixture) when fed as a 10% soln in corn oil/ [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 438]**PEER REVIEWED**
  
• LD50 Rat (female) oral 470 mg/kg /a 92% product (a cis:trans mixture) when fed as a 10% soln in corn oil/ [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 438]**PEER REVIEWED**
  
• LD50 Rat skin 775 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1125]**PEER REVIEWED**
  
• LD50 Rat ip 175 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1125]**PEER REVIEWED**
  
• LC50 Mouse inhalation 4650 mg/cu m/2 hr [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1125]**PEER REVIEWED**
  
• LD50 Mouse (CD1) oral 215 mg/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.76 (1993)]**PEER REVIEWED**
  
• LD50 Mouse (JCL:ICR, male) oral 640 mg/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.76 (1993)]**PEER REVIEWED**
  
• LD50 Mouse (JCL:ICR, female) oral 640 mg/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.76 (1993)]**PEER REVIEWED**
  
• LD50 Rat (Fischer 344) oral 94 mg/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.76 (1993)]**PEER REVIEWED**
  
• LD50 Rat (CD) oral 127 mg/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.76 (1993)]**PEER REVIEWED**
  
• LD50 Rat (Wistar, male) oral 560 mg/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.76 (1993)]**PEER REVIEWED**
  
• LD50 Rat (Wistar, female) oral 510 mg/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.76 (1993)]**PEER REVIEWED**
  
• LC50 Rat (Wistar) inhalation 3309.7 mg/cu m/4 hr /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.77 (1993)]**PEER REVIEWED**
  
• LC50 Rat (Fischer 344, male) inhalation 3041.8 mg/cu m/4 hr /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.77 (1993)]**PEER REVIEWED**
  
• LC50 Rat (Fischer 344, female) inhalation 3337.8 mg/cu m/4 hr /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.77 (1993)]**PEER REVIEWED**
  
• LC50 Rat (Crb:CD(SD)Br, male) inhalation 4880.5 mg/cu m/4 hr /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.77 (1993)]**PEER REVIEWED**
  
• LC50 Rat (Crb:CD(SD)Br, female) inhalation 5402.6 mg/cu m/4 hr /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.77 (1993)]**PEER REVIEWED**
  
• LD50 Mouse (JCL:ICR) dermal >1.211 g/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.78 (1993)]**PEER REVIEWED**
  
• LD50 Mouse (JCL:ICR, male) subcutaneous 0.33 g/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.78 (1993)]**PEER REVIEWED**
  
• LD50 Mouse (JCL:ICR, female) subcutaneous 0.345 g/kg bw /From table/ [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.78 (1993)]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• Absorption through skin occurred particularly when the liquid was confined or when in propylene glycol solution which retarded evaporation. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 4227]**PEER REVIEWED**
  
• ... Significant differences are apparent in the elimination rates of the cis and trans /isomers/ of 1,3-dichloropropene. /cis- and trans-1,3-Dichloropropene/ [USEPA; Ambient Water Quality Criteria Doc: Dichloropropanes/Dichloropropenes (Draft) p.C-27 (1980)]**PEER REVIEWED**
  
• Kinetic data on the uptake of vapors of technical grade 1,3-dichloropropene (DCP) & resultant cis- & trans-1,3-dichloropropene blood concns were obtained in rats exposed to 30, 90, 300, or 900 ppm 1,3-dichloropropene for 3 hr. The uptake of 1,3-dichloropropene did not incr proportionately with increasing exposure concn due to an exposure level related decr in the respiratory ventilatory frequency of rats exposed to > or = 90 ppm 1,3-dichloropropene & the saturation of metab of 1,3-dichloropropene by rats exposed to > or = 300 ppm 1,3-dichloropropene. Absorption of inhaled 1,3-dichloropropene occurred primarily in the lower respiratory tract, although a small amount of the chemical was absorbed via the nasal mucosa, a known target tissue of inhaled 1,3-dichloropropene in rats. Following absorption, both isomers of 1,3-dichloropropene were, at < or = 300 ppm exposure levels, rapidly eliminated from the bloodstream (3-6 min half-life). In addn, data obtained in rats exposed to 300 ppm 1,3-dichloropropene revealed that this rapid elimination phase was followed by a slower elimination phase having a 33-34 min half-life. Rats exposed to 900 ppm vapors also eliminated 1,3-dichloropropene in a biphasic manner; however, in this case the blood half-life of 1,3-dichloropropene during the initial phase of excretion was 14-27 min. Exposure of 90 ppm 1,3-dichloropropene also produced a significant decr in renal (31%) & hepatic (41%), but not pulmonary, nonprotein sulfhydryl content. [Stott WT, Kastl PE; Toxicol Appl Pharmacol 85 (3): 332-41 (1986)]**PEER REVIEWED**
  
• A biological monitoring study was carried out in the Dutch flower-bulb culture to determine the relationship between respiratory occupational exposure to Z- and E-1,3-dichloropropene and urinary excretion of two mercapturic acid metabolites, N-acetyl-S-(Z- and E-3-chloropropenyl-2)-L-cysteine. Urinary excretion of N-acetyl-S-(Z-3-chloropropenyl-2)-L-cysteine and N-acetyl-S-(E-3-chloropropenyl-2)-L-cysteine, either based on excretion rates or on creatinine excretion, followed first order elimination kinetics after exposure. Urinary half-lives of elimination were 5.0 + or - 1.2 hr for N-acetyl-S-(Z-3-chloropropenyl-2)-L-cysteine and 4.7 + or - 1.3 hr for N-acetyl-S-(E-3-chloropropenyl-2)-L-cysteine and were not statistically significantly different. Calculated coefficients of variation indicated that the half-life of elimination of N-acetyl-S-(Z-3-chloropropenyl-2)-L-cysteine and N-acetyl-S-(E-3-chloropropenyl-2)-L-cysteine were quite consistent inter- and intra-individually. Strong correlations (r > 0.93) were observed between respiratory 8 hour time weighted average (TWA) exposure to Z- and E-1,3-dichloropropene and complete cumulative urinary excretion of N-acetyl-S-(Z-3-chloropropenyl-2)-L-cysteine and N-acetyl-S-(E-3-chloropropenyl-2)-L-cysteine. Z-DCP yielded three times more mercapturic acid than E-1,3-dichloropropene, probably due to differences in metabolism. Z-1,3-dichloropropene and E-1,3-dichloropropene were excreted 45 and 14% as their respective mercapturic acid metabolites. A respiratory 8 hour TWA exposure to the Dutch occupational exposure limit of 5 mg M(-3) 1,3-Dichloropropene would result in a complete cumulative excretion of 14.4 mg (95% confidence interval: 11.7 - 17.0 mg) N-acetyl-S-(Z-3-chloropropenyl-2)-L-cysteine and 3.2 mg (95% confidence interval: 2.3-4.1 mg) N-acetyl-S-(E-3-chloropropenyl-2)-L-cysteine. [Van Welie R TH et al; Arch Environ Contam Toxicol 20 (1): 6-12 (1991)]**PEER REVIEWED**
  
• Groups of 8 adult Fischer 344 rats/sex were given non radiolabelled 1,3-dichloropropene at 5 mg/kg bw, in corn oil, by gavage, for 14 consecutive days, prior to a single dose of 5 mg 14C-1,3-dichloropropene/kg bw (actual 4.5 mg) (uniformly labeled) (96.3%; 53.3% cis- & 43.0% trans-), administered to 5 out of the 8 rats on day 15. The remaining 3 rats/sex were sacrificed. The distribution of radioactivity found in the tissues (4-6%) of repeatedly dosed rats, 2 rats of each sex, which had not been previously dosed, received a single gavage dose of 5 mg 14C-1,3-dichloropropene/kg bw. The urine was the major route of elimination of the radioactivity derived from 14C-1,3-dichloropropene, which ranged from 60-65% of the administered dose in 48 hr in the rats with repeated doses & a single dose. Elimination of 1,3-dichloropropene as 14/carbon dioxide/ was approx (average) 26% of the administrated radioactivity with about 4-5% of the dose eliminated in the feces, for all groups. [WHO; Environ Health Criteria 146: 1,3-Dichloropropene, 1,2-Dichloropropane and Mixtures p.60 (1993)]**PEER REVIEWED**
  
• In rats, 1,3-dichloropropene is absorbed rapidly, after either inhalation or oral administration, and is eliminated principally by metabolism (glutathione conjugation) within 24-48 hours. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 935 (1999)]**PEER REVIEWED**
  

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Metabolism/Metabolites

• The major urinary metabolite in rats given 1,3-dichloro-2-propene was a mercapturic acid. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-142]**PEER REVIEWED**
  
• The biotransformation to sulfur containing products of the Z-isomers & E-isomers of 1,3-dichloropropene administered ip in combination to male Wistar-rats was investigated. The presence of mercapturic acids in the urine of the animals was determined using GC with nitrogen & sulfur selective detection (GC-NDP & GC-FDP, respectively) & GC/MS with negative chemical ionization & single ion detection. Quantification of mercapturic acids in the urine of animals treated with the dichloropropene isomers in doses of 5 ug each, was achieved with the use of GC-NDP & GC-FPD, while GC/negative chemical ionization/MS detected only the mercapturic acids generated by doses = 25 ug or higher, due to the interference of endogenous products. Both products tested are metabolized via glutathione conjugation, with the generation of 2 major mercapturic acid conjugates, & that all three analytical procedures tested are useful for the determination of human exposure to low levels of 1,3-dichloropropene. [Onkenhout W et al; Archives of Toxicol 59 (4): 235-241 (1986)]**PEER REVIEWED**
  
• A study of the relationship between air dichloropropene (DCP) concns & urinary excretion of N-acetyl-S-(cis-3-chloroprop-2-enyl)cysteine (3CNAC) & N-acetylglucosaminidase (NAG) in DCP fumigators was conducted. The study group consisted of male dichloropropene applicators. Breathing zone samples were analyzed for dichloropropene. Urine samples were collected before & at various times after application & analyzed for 3CNAC & NAG. Air DCP concns ranged from 0.26-9.39 mg/cu m, mean 2.56 mg/cu m. Duration of exposure ranged from 120-697 min. This yielded DCP air exposure products of 62-3700 mg/cu m/min. 24 hr urinary excretion of 3 CNAC ranged from 0.50-9.17 mg, mean 2.57 mg. 24 hr 3CNAC excretion correlated well with the DCP air exposure product, correlation coefficient 0.854. The correlation was improved when the next morning urine samples were used, correlation coefficient 0.914. The overall mean excretion of NAG was 2.63 mU/mg creatinine. 4 subjects had NAG values above 4 mU/mg, a value considered to be clinically abnormal. 9 subjects had increases in NAG activity that averaged 25% higher than the baseline value. 3CNAC concns in the next morning urine were positively correlated with 24 hr excretion of NAG. [Osterloh JD et al; Archives of Environ Health 44 (4): 207-13 (1989)]**PEER REVIEWED**
  
• The relationship between the concn of inhaled 1,3-dichloropropene and urinary excretion of the mercapturic acid conjugate was examined. Male Sprague Dawley rats were exposed nose only to 1,3-dichloropropene at dose levels of 0, 40, 106, 284, 398 or 788 ppm for 1 hr. Exposures were conducted in a nose only exposure system housed in a carcinogen glove box. The volume of urine excreted per rat in the 24 hr period after exposure to 1,3-dichloropropene was significantly affected only after exposure to 284 ppm. The excretion levels of the mercapturic acid conjugate N-acetyl-S(cis-3-chloroprop-2-enyl)cysteine at all exposure concn were significantly different from controls. With increasing exposure concn from 0 to 284 ppm, N-acetyl-S(cis-3-chloroprop-2-enyl)cysteine levels increased; from 284 to 789 ppm, N-acetyl-S(cis-3-chloroprop-2-enyl)cysteine levels were not significantly different. The authors conclude that at the lower exposure levels, urinary excretion of N-acetyl-S(cis-3-chloroprop-2-enyl)cysteine was dependent on 1,3-dichloropropene concn. [Fisher GD, Kilgore WW; Fund Appl Toxicol 112: 300-7 (1988)]**PEER REVIEWED**
  
• Levels of glutathione in various tissues were studied in male Sprague-Dawley rats following acute inhalation exposure to 1,3-dichloropropene for 1 hr in a dynamic, nose only system. Glutathione content was determined in nasal tissue, heart, kidney, liver, lung, & testes. No 1,3-dichloropropene was detected in the blood of rats 2 hr after exposure to up to 955 ppm 1,3-dichloropropene. When one rat was exposed to 100 mg/kg 1,3-dichloropropene orally, both cis & trans isomers of 1,3-dichloropropene were detected in the blood 2 hr after exposure. Nasal tissue glutathione content was decreased to 27% of control at 5 ppm 1,3-dichloropropene, to 23% at 31 ppm, to 18% at 71 ppm, & to 12% at 223 ppm. In lung tissue, glutathione content remained relatively constant at 68 to 82% of control after exposure of 2-955 ppm 1,3-dichloropropene. Exposure to up to 955 ppm 1,3-dichloropropene had little or no effect on the glutathione levels of heart & testes. Significantly decreased glutathione levels in heart, lung, liver, & testes were observed after exposure to 1716 ppm 1,3-dichloropropene. A concn dependent decr of glutathione levels in the liver was observed for exposure between 772 & 1716 ppm 1,3-dichloropropene. No change in lung wet wt was observed for any exposure. Serum lactate dehydrogenase activity, when measured 6 hr after 1,3-dichloropropene exposure, was decreased only for the highest 1,3-dichloropropene concn. The results showed that, at least at low levels, 1,3-dichloropropene was detoxified by conjugation to glutathione in nasal tissue. [Fisher GD, Kilgore WW; J Toxicol Environ Health 23 (2): 171-82 (1988)]**PEER REVIEWED**
  
• Oral admin of 1,3-dichloropropene to rats or mice resulted in significant, dose-related reductions in the levels of non-protein sulfhydryls (NPS) (indicator of tissue glutathione concn) in the forestomach & to a lesser extent in the glandular stomach & liver. [WHO; Environ Health Criteria 146: 1,2-Dichloropropene, 1,3-Dichloropropane and Mixture p.61 (1993)]**PEER REVIEWED**
  
• 1,3-Dichloropropene was given in doses of 0, 25, 50 and 75 mg/kg body weight intraperitoneally to male fischer 344 rats. Excretion of the metabolite N-acetyl-S-(cis-3-chloroprop-2-enyl)-L-cysteine increased in a dose-dependent manner from 0 to 50 mg/kg 1,3-dichloropropene, but no further increase was seen at the 75 mg/kg dose, suggesting that, at higher doses, the metabolism pathway may be saturated or impaired. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 936 (1999)]**PEER REVIEWED**
  
• The major urinary metabolite in rats given 1,3-dichloro-2-propene was a mercapturic acid. Apparently the chlorine in the 1-position is removed prior to conjugation with cysteine. Formation of a glutathione conjugate was shown in an in vitro system. Although this conjugation appears to require the enzyme hepatic glutathione transferase /while/ many other molecules with electrophilic centers also form glutathione conjugates nonenzymatically. ... Perhaps alkylation of critical proteins is the molecular basis of the widespread visceral lesions in D-D poisoning. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-142]**PEER REVIEWED**
  
• The metabolism of cysteine S-conjugates of both cis- and trans-1,3-dichloropropene in the presence of rat kidney microsomes and purified flavin-containing monooxygenase from hog liver was investigated in vitro. Preliminary studies with isolated rat kidney cells demonstrated that cysteine S-conjugates were quite toxic to the cells in a process which was consistent with a role of the flavin-containing monooxygenase in the bioactivation of the nephrotoxins. Putative S-oxide metabolites of cysteine S-conjugates were chemically synthesized, and diastereomers were separated and identified by spectroscopic means. The metabolic products of cysteine S-conjugates were identified by comparing the chemical properties of the metabolites with authentic synthetic cysteine S-conjugate S-oxides. Surprisingly, S-conjugate S-oxygenase activity was not observed with rat kidney microsomes but was present when cysteine S-conjugates were incubated with the highly purified flavin containing monooxygenase from hog liver. The kinetic parameters indicated that considerable S-oxygenase stereoselectivity and structural selectivity was observed: cis cysteine S-conjugates were preferred substrates and N-acetylation of cysteine S-conjugates decreased substrate activity. S-Oxygenation was considerably diastereoselective and diastereoselectivity was much greater for cysteine S-conjugates with higher Vmax values. Cysteine S-conjugate S-oxides were not indefinitely stable, and under certain conditions, the S-oxides underwent a (2,3)-sigmatropic rearrangement to acrolein. Formation of acrolein or other electrophilic products from S-(chloropropenyl)cysteine conjugate S-oxides may contribute to the renal effects observed for S-(chloropropenyl)cysteine conjugates. Thus, cytotoxicity studies with isolated rat proximal tubular cells or LLC-PK1 cells treated with cysteine S-conjugates showed a time and dose-dependent decrease in cell viability. Reduction of renal cytotoxicity of cysteine S-conjugates in the presence of methimazole, an alternate substrate competitive inhibitor of the flavin containing monooxygenase, suggested that this enzyme may contribute to the renal effects of 1,3-dichloropropene. [Park SB et al; Chem Res Toxicol 5 (2): 193-201 (1992)]**PEER REVIEWED**
  

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.