The Registry of Toxic Effects of Chemical Substances

Ether, 2,4 - dichlorophenyl p - nitrophenyl

RTECS #: KN8400000

CAS #: 1836-75-5

UPDATE: May 2005 MW: 284.10 MF: C12H7Cl2NO3


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. MUTATION DATA:
  3. REPRODUCTIVE EFFECTS DATA:
  4. TUMORIGENIC DATA:
  5. ACUTE TOXICITY DATA:
  6. OTHER MULTIPLE DOSE DATA:
  7. REVIEWS:
  8. STANDARDS AND REGULATIONS:
  9. STATUS IN FEDERAL AGENCIES:
  10. REFERENCES:

SYNONYMS:

  1. 2',4' - Dichloro - 4 - nitrobiphenyl ether
  2. 2,4 - Dechlorophenyl p - nitrophenyl ether
  3. 2,4 - Dichloro - 1 - (4 - nitrophenoxy) benzene
  4. 2,4 - Dichloro - 4' - nitrodiphenyl ether
  5. 2,4 - Dichlorophenyl 4 - nitrophenyl ether
  6. 2,4 - Dichlorophenyl p - nitrophenyl ether
  7. 2,4 - Dichlorphenyl - 4 - nitrophenylaether (German)
  8. 4' - Nitro - 2,4 - dichlorodiphenyl ether
  9. 4 - (2,4 - Dichlorophenoxy) nitrobenzene
  10. Benzene, 2,4 - dichloro - 1 - (4 - nitrophenoxy) -
  11. FW 925
  12. Mezotox
  13. NCI - C00420
  14. NE
  15. NIP
  16. Niclofen
  17. Nitofen
  1. Nitrafen
  2. Nitraphen
  3. Nitrochlor
  4. Nitrofen
  5. Nitrofene (French)
  6. Nitrophen
  7. Nitrophene
  8. Preparation 125
  9. TOK
  10. TOK E
  11. TOK E 40
  12. TOK E - 25
  13. TOK WP - 50
  14. TOK - 2
  15. Tokkorn
  16. Trizilin
  17. Trizilin 25


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
mutation in microorganisms Salmonella typhimurium 33,300 ng/plate (+enzymatic activation step) ENMUDM 7(Suppl 5),1,1985
morphological transform rat embryo 1,500 ng/plate JJATDK 1,190,1981
phage inhibition capacity Escherichia coli 4,460 µmol/L MUREAV 182,193,1987
phage inhibition capacity Escherichia coli 35.7 mmol/L (+enzymatic activation step) EMMUEG 36,206,2000
sister chromatid exchange hamster lung 12.5 µmol/L/32 hour MUREAV 580,41,2005


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
rat 		lowest published toxic concentration: 23 mg/m3 (2-5 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Specific developmental abnormalities: Urogenital system 		VCVGK* -,312,1994
oral
mouse 		lowest published toxic dose: 660 mg/kg (5-15 day pregnant) Reproductive: Specific developmental abnormalities: Respiratory system

Reproductive: Effects on newborn: Weaning or lactation index (e.g., # alive at weaning per # alive at day 4) 		TJADAB 24(1),11A,1981
oral
mouse 		lowest published toxic dose: 1,100 mg/kg (7-17 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive)

Reproductive: Effects on newborn: Physical

Reproductive: Effects on newborn: Delayed effects 		SCIEAS 215,293,1982
oral
mouse 		lowest published toxic dose: 660 mg/kg (5-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Effects on newborn: Physical 		NMJOAA 31,115,1986
oral
mouse 		lowest published toxic dose: 68,750 µg/kg (7-17 day pregnant) Reproductive: Other developmental abnormalities

Reproductive: Effects on newborn: Physical 		TXAPA9 67,1,1983
oral
mouse 		lowest published toxic dose: 550 mg/kg (7-17 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive) TXAPA9 67,1,1983
oral
mouse 		lowest published toxic dose: 2,520 mg/kg (1-21 day pregnant) Reproductive: Specific developmental abnormalities: Body wall

Reproductive: Specific developmental abnormalities: Respiratory system

Reproductive: Specific developmental abnormalities: Hepatobiliary system 		TJADAB 32,45B,1985
oral
rat 		lowest published toxic dose: 62,500 µg/kg (6-15 day pregnant) Reproductive: Specific developmental abnormalities: Body wall

Reproductive: Specific developmental abnormalities: Respiratory system

Reproductive: Specific developmental abnormalities: Urogenital system 		JACTDZ 4(1),221,1985
oral
rat 		lowest published toxic dose: 150 mg/kg (7-12 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) TCMUD8 6,339,1986
oral
rat 		lowest published toxic dose: 37,530 µg/kg (6-18 day pregnant) Reproductive: Effects on newborn: Physical TXCYAC 34,285,1985
oral
rat 		lowest published toxic dose: 62,500 µg/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) TJADAB 34,213,1986
oral
rat 		lowest published toxic dose: 100 mg/kg (11 day pregnant) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) TXCYAC 20,209,1981
oral
rat 		lowest published toxic dose: 80 mg/kg (10-13 day pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Effects on newborn: Stillbirth

Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive) 		TXAPA9 86,22,1986
oral
rat 		lowest published toxic dose: 825 mg/kg (8-18 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death VCVGK* -,313,1994
oral
rat 		lowest published toxic dose: 1,650 mg/kg (8-18 day pregnant) Reproductive: Specific developmental abnormalities: Urogenital system

Reproductive: Other developmental abnormalities

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) 		VCVGK* -,313,1994
oral
rat 		lowest published toxic dose: 550 mg/kg (8-18 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive)

Reproductive: Specific developmental abnormalities: Respiratory system 		VCVGK* -,313,1994
oral
rat 		lowest published toxic dose: 250 mg/kg (11 day pregnant) Reproductive: Specific developmental abnormalities: Endocrine system TXAPA9 73,323,1984
oral
rat 		lowest published toxic dose: 500 mg/kg (6-15 day pregnant) Reproductive: Specific developmental abnormalities: Body wall NTIS** #PB84-193879
skin
mouse 		lowest published toxic dose: 175 mg/kg (8 day pregnant) Reproductive: Effects on newborn: Other neonatal measures or effects JPFCD2 21,303,1986
skin
mouse 		lowest published toxic dose: 160 mg/kg (8 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive) TXCYAC 40,297,1986
skin
mouse 		lowest published toxic dose: 286 mg/kg (8 day pregnant) Reproductive: Specific developmental abnormalities: Endocrine system JPFCD2 21,303,1986
skin
mouse 		lowest published toxic dose: 1,100 mg/kg (7-17 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive) TJADAB 25(2),45A,1982
skin
rat 		lowest published toxic dose: 12 mg/kg (6-15 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Respiratory system 		TXCYAC 28,37,1983
skin
rat 		lowest published toxic dose: 120 mg/kg (6-15 day pregnant) Reproductive: Specific developmental abnormalities: Body wall

Reproductive: Specific developmental abnormalities: Endocrine system

Reproductive: Specific developmental abnormalities: Urogenital system 		TXCYAC 28,37,1983
skin
rat 		lowest published toxic dose: 120 mg/kg (6-15 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive)

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) 		TXCYAC 28,37,1983
unreported route
hamster 		lowest published toxic dose: 500 mg/kg (7-11 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Urogenital system 		TJADAB 25(2),45A,1982
unreported route
mouse 		lowest published toxic dose: 550 mg/kg (7-17 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear TJADAB 25(2),45A,1982
unreported route
mouse 		lowest published toxic dose: 1,100 mg/kg (7-17 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive) TJADAB 25(2),45A,1982
unreported route
rat 		lowest published toxic dose: 13,900 µg/kg (7-16 day pregnant) Reproductive: Specific developmental abnormalities: Body wall TJADAB 25(2),45A,1982
unreported route
rat 		lowest published toxic dose: 125 mg/kg (7-16 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear TJADAB 25(2),45A,1982
unreported route
rat 		lowest published toxic dose: 220 mg/kg (8-18 day pregnant) Reproductive: Specific developmental abnormalities: Respiratory system PHMCAA 19,178,1977
unreported route
rat 		lowest published toxic dose: 352 mg/kg (8-18 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive) PHMCAA 19,178,1977
unreported route
rat 		lowest published toxic dose: 37.53 mg/kg (8-16 day pregnant) Reproductive: Other developmental abnormalities HBPTO* 1,740,2001


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 24 gm/kg/12 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors

Lung, Thorax, or Respiration: Tumors 		JJIND8 65,937,1980
oral
mouse 		toxic dose : 200 gm/kg/78 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Vascular: Tumors

Liver: Tumors 		NCITR* NCI-TR-184,1979
oral
mouse 		toxic dose : 308 gm/kg/78 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Vascular: Tumors

Liver: Tumors 		NCITR* NCI-TR-26,1978
oral
mouse 		toxic dose : 114 gm/kg/58 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Vascular: Tumors

Liver: Tumors 		NCITR* NCI-TR-26,1978
oral
mouse 		toxic dose : 47 gm/kg/12 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors

Lung, Thorax, or Respiration: Tumors 		JJIND8 65,937,1980
oral
rat 		lowest published toxic dose: 42 gm/kg/94 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Vascular: Tumors

Liver: Tumors 		NCITR* NCI-TR-26,1978


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
cat 		lowest published lethal concentration: 620 mg/m3/4 hour Behavioral: Excitement

Lung, Thorax, or Respiration: Dyspnea

Gastrointestinal: Changes in structure or function of salivary glands 		HYSAAV 32(1),20,1967
oral
cat 		lowest published lethal dose: 300 mg/kg N/R HYSAAV 32(1),20,1967
oral
mouse 		lethal dose (50 percent kill): 450 mg/kg Behavioral: Excitement

Lung, Thorax, or Respiration: Respiratory stimulation

Nutritional and Gross Metabolic: Body temperature increase 		HYSAAV 32(1),20,1967
oral
mouse 		lethal dose (50 percent kill): 8,250 mg/kg Behavioral: Somnolence (general depressed activity)

Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Hypermotility, diarrhea 		VCVGK* -,312,1984
oral
rat 		lethal dose (50 percent kill): 740 mg/kg Behavioral: Excitement

Lung, Thorax, or Respiration: Respiratory stimulation

Nutritional and Gross Metabolic: Body temperature increase 		HYSAAV 32(1),20,1967
oral
rat 		lethal dose (50 percent kill): 7,850 mg/kg Behavioral: Somnolence (general depressed activity)

Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Hypermotility, diarrhea 		VCVGK* -,312,1984
oral
rat 		lowest published toxic dose: 250 mg/kg Endocrine: Other changes

Endocrine: Evidence of thyroid hypofunction 		TXAPA9 73,323,1984
oral
rabbit 		lethal dose (50 percent kill): 1,620 mg/kg N/R 28ZEAL 5,166,1976
oral
rabbit 		lethal dose (50 percent kill): 2,650 mg/kg Behavioral: Somnolence (general depressed activity)

Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Hypermotility, diarrhea 		VCVGK* -,312,1984
oral
woman 		lowest published lethal dose: 10 mL/kg Behavioral: Convulsions or effect on seizure threshold

Behavioral: Coma

Lung, Thorax, or Respiration: Respiratory depression 		VHTODE 43,212,2001
skin
rat 		lethal dose (50 percent kill): 5 gm/kg N/R AEHLAU 28,316,1974
skin
rabbit 		lowest published lethal dose: 3,270 mg/kg N/R TXCYAC 29,1,1983
unreported route
rat 		lethal dose (50 percent kill): 3 gm/kg N/R 30ZDA9 -,109,1971
unreported route
rat 		lowest published toxic dose: 250 mg/kg Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) HBPTO* 1,740,2001


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
cat 		lowest published toxic concentration: 26 mg/m3/4 hour/7 week- intermittent Blood: Pigmented or nucleated red blood cells

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Catalases

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		GISAAA 32(1),19,1967
inhalation
mammal (species unspecified) 		lowest published toxic concentration: 18 mg/m3/4 hour/122 day- intermittent Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		VCVGK* -,313,1994
oral
dog 		lowest published toxic dose: 1,400 mg/kg/4 week- continuous Liver: Changes in liver weight TXAPA9 19,263,1971
oral
dog 		lowest published toxic dose: 36,400 mg/kg/2 year- continuous Liver: Changes in liver weight FCTXAV 10,427,1972
oral
rat 		lowest published toxic dose: 13,650 mg/kg/13 week- continuous Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight

Related to Chronic Data: Changes in testicular weight 		TXAPA9 19,263,1971
oral
rat 		lowest published toxic dose: 40,740 mg/kg/13 week- continuous Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight 		FCTXAV 10,427,1972
oral
rat 		lowest published toxic dose: 40,740 mg/kg/97 week- continuous Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		TXAPA9 19,263,1971
oral
rat 		lowest published toxic dose: 68,320 mg/kg/305 day- intermittent Nutritional and Gross Metabolic: Weight loss or decreased weight gain VCVGK* -,313,1994
unreported route
rat 		lowest published toxic dose: 1,500 mg/kg/3 day- continuous Endocrine: Evidence of thyroid hyperfunction HBPTO* 1,740,2001


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
International Agency for Research on Cancer (IARC) Cancer Review Animal Sufficient Evidence IMEMDT 30,271,1983
International Agency for Research on Cancer (IARC) Cancer Review Human No Adequate Data IMEMDT 30,271,1983
International Agency for Research on Cancer (IARC) Cancer Review Group 2B IMSUDL 7,56,1987
TOXICOLOGY REVIEW
APLMAS 107,54,1983
TOXICOLOGY REVIEW
MUREAV 567,227,2004


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Occupational Exposure Limit - FINLAND Carcinogen, JAN1999
Occupational Exposure Limit - RUSSIA short term exposure limit 1 mg/m3, JAN1993
Occupational Exposure Limit - UNITED KINGDOM Carcinogen, SEP2000
Occupational Exposure Limit - UNITED KINGDOM time-weighted average 1 ppm (7.1 mg/m3), SEP2000


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
N/R N/R N/R


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat
EPA GENETOX PROGRAM 1988, Inconclusive: Mammalian micronucleus
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as a pre-and postemergence herbicide in agricultural applications
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NCI Carcinogenesis Bioassay (feed);clear evidence:mouse,rat NCITR* NCI-TR-26,1978
NCI Carcinogenesis Bioassay (feed);clear evidence:mouse NCITR* NCI-TR-184,1979
NCI Carcinogenesis Bioassay (feed);no evidence:rat NCITR* NCI-TR-184,1979
NTP 11th Report on Carcinogens,2004:Reasonably anticipated to be a human carcinogen


REFERENCES:

CODEN
REFERENCE
28ZEAL "Pesticide Index," Frear, E.H., ed., State College, PA, College Science Pub., 1969
30ZDA9 "Chemistry of Pesticides," Melnikov, N.N., New York, Springer-Verlag New York, Inc., 1971
AEHLAU Archives of Environmental Health. (Heldref Pub., 4000 Albemarle St., NW, Washington, DC 20016) V.1- 1960-
APLMAS Archives of Pathology and Laboratory Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1-5(2), 1926-28; V.100- 1976-
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
ENMUDM Environmental Mutagenesis. (New York, NY) V.1-9, 1979-87. For publisher information, see EMMUEG.
FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7.
GISAAA Gigiena i Sanitariya. For English translation, see HYSAAV. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1936-
HBPTO* Handbook of pesticide toxicology. Robert Krieger ed, Academic press, 2001
HYSAAV Hygiene and Sanitation (USSR). English translation of GISAAA. (Springfield, VA) 1964-71. Discontinued.
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979-
JACTDZ Journal of the American College of Toxicology. (Mary Ann Liebert, Inc., 1651 Third Ave., New York, NY 10128) V.1-12, 1982-1993. Discontinued.
JJATDK JAT, Journal of Applied Toxicology. (John Wiley & Sons Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK) V.1- 1981-
JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ.
JPFCD2 Journal of Environmental Science and Health, Part B: Pesticides, Food Contaminants, and Agricultural Wastes. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.B11- 1976-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*.
NMJOAA Nagoya Medical Journal. (Nagoya City Univ. Medical School, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan) V.1- 1953-
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
PHMCAA Pharmacologist. (American Soc. for Pharmacology and Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20014) V.1- 1959-
SCIEAS Science. (American Assoc. for the Advancement of Science, 1333 H St., NW, Washington, DC 20005) V.1- 1895-
TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980-
TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973-
VCVGK* "Vrednie chemichescie veshestva, galogen I kislorod sodergashie organicheskie soedinenia". (Hazardous substances. Galogen and oxygen containing substances), Bandman A.L. et al., Chimia, 1994.
VHTODE Veterinary and Human Toxicology. (American College of Veterinary and Comparative Toxicology, Publication Office, Comparative Toxicology, Manhattan, KS 66506) V.19- 1977-

Used as a pre-and postemergence herbicide in agricultural applications

RTECS Compound Description:
   Agricultural Chemical
   Tumorigen
   Drug
   Mutagen
   Reproductive Effector
   Human Data

ALT CAS #: 51274-07-8
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