*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : TK7912300
CHEMICAL NAME : Piperazine,
1-acetyl-4-(4-((2-(2,4-dichlorophenyl)-2-(1H-imidazol
-1-ylmethyl)-1,3-diox olan- 4-yl)methoxy)phenyl)-,
cis-
CAS REGISTRY NUMBER : 65277-42-1
BEILSTEIN REFERENCE NO. : 4303081
LAST UPDATED : 199612
DATA ITEMS CITED : 31
MOLECULAR FORMULA : C26-H28-Cl2-N4-O4
MOLECULAR WEIGHT : 531.48
WISWESSER LINE NOTATION : T6N DNTJ AV1 DR DO1- DT5O COTJ BR BG DG& B1- AT5N CNJ
COMPOUND DESCRIPTOR : Drug
Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Fungarest
* Fungoral
* Ketoconazol
* Ketoconazole
* Ketoderm
* Ketoisdin
* KW-1414
* Nizoral
* Orifungal M
* Panfungol
* R 41400
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 45 mg/kg/17D-I
TOXIC EFFECTS :
Behavioral - coma
Liver - jaundice, other or unclassified
REFERENCE :
GUTTAK Gut. (British Medical Journal, Box 560B, Kennebunkport, ME 04046)
V.1- 1960- Volume(issue)/page/year: 26,636,1986
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 412 mg/kg/15W-I
TOXIC EFFECTS :
Behavioral - coma
Liver - hepatitis (hepatocellular necrosis), diffuse
Liver - jaundice, other or unclassified
REFERENCE :
GUTTAK Gut. (British Medical Journal, Box 560B, Kennebunkport, ME 04046)
V.1- 1960- Volume(issue)/page/year: 26,636,1986
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 264 mg/kg/66D-I
TOXIC EFFECTS :
Liver - other changes
REFERENCE :
GASTAB Gastroenterology. (Academic Press, Inc., 1 E. First St., Duluth, MN
55802) V.1- 1943- Volume(issue)/page/year: 86,503,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - child
DOSE/DURATION : 450 mg/kg/90D-I
TOXIC EFFECTS :
Endocrine - evidence of thyroid hypofunction
Nutritional and Gross Metabolic - other changes
REFERENCE :
BMJOAE British Medical Journal. (British Medical Assoc., BMA House,
Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year:
293,993,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 49 mg/kg/17D-I
TOXIC EFFECTS :
Liver - other changes
REFERENCE :
GASTAB Gastroenterology. (Academic Press, Inc., 1 E. First St., Duluth, MN
55802) V.1- 1943- Volume(issue)/page/year: 86,503,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 60 mg/kg
TOXIC EFFECTS :
Liver - other changes
REFERENCE :
GASTAB Gastroenterology. (Academic Press, Inc., 1 E. First St., Duluth, MN
55802) V.1- 1943- Volume(issue)/page/year: 86,503,1984
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 166 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
MDACAP Medicamentos de Actualidad. (J.R. Prous, S.A., Apartado de Correos
540, 08080 Barcelona, Spain) V.1- 1965- Volume(issue)/page/year:
17,373,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1474 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho
Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
Volume(issue)/page/year: 18,474,1987
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >2400 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho
Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
Volume(issue)/page/year: 18,474,1987
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 86 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
DRUGAY Drugs. International Journal of Current Therapeutics and Applied
Pharmacology Reviews. (ADIS Press International Inc., Suite B-30, Oxford
Ct. Business Center, 582 Middletown Blvd., Langhorne, PA 19047) V.1- 1971-
Volume(issue)/page/year: 23,1,1982
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 618 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
MDACAP Medicamentos de Actualidad. (J.R. Prous, S.A., Apartado de Correos
540, 08080 Barcelona, Spain) V.1- 1965- Volume(issue)/page/year:
17,373,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 2937 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho
Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
Volume(issue)/page/year: 18,474,1987
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >4 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho
Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
Volume(issue)/page/year: 18,474,1987
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 32 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
AMACCQ Antimicrobial Agents and Chemotherapy. (American Soc. for
Microbiology, 1913 I St., NW, Washington, DC 20006) V.1- 1972-
Volume(issue)/page/year: 33,895,1989
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 178 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
MDACAP Medicamentos de Actualidad. (J.R. Prous, S.A., Apartado de Correos
540, 08080 Barcelona, Spain) V.1- 1965- Volume(issue)/page/year:
17,373,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 23300 ug/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
MDACAP Medicamentos de Actualidad. (J.R. Prous, S.A., Apartado de Correos
540, 08080 Barcelona, Spain) V.1- 1965- Volume(issue)/page/year:
17,373,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - guinea pig
DOSE/DURATION : 178 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
MDACAP Medicamentos de Actualidad. (J.R. Prous, S.A., Apartado de Correos
540, 08080 Barcelona, Spain) V.1- 1965- Volume(issue)/page/year:
17,373,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - guinea pig
DOSE/DURATION : 23300 ug/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
MDACAP Medicamentos de Actualidad. (J.R. Prous, S.A., Apartado de Correos
540, 08080 Barcelona, Spain) V.1- 1965- Volume(issue)/page/year:
17,373,1981
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 1200 mg/kg/30D-I
TOXIC EFFECTS :
Liver - other changes
Liver - changes in liver weight
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 18,1426,1984
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE : 1029 mg/kg
SEX/DURATION : male 60 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - other effects on male
Endocrine - androgenic
REFERENCE :
ACENA7 Acta Endocrinologica (Copenhagen). (Periodica, Skolegade 12 E,
DK-2500 Valby, Denmark) V.1- 1948- Volume(issue)/page/year: 110,276,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 6480 mg/kg
SEX/DURATION : male 9 week(s) pre-mating
female 2 week(s) pre-mating - 7 day(s) after
conception
TOXIC EFFECTS :
Reproductive - Fertility - mating performance (e.g. # sperm positive females
per # females mated; # copulations per # estrus cycles)
Reproductive - Fertility - female fertility index (e.g. # females pregnant
per # sperm positive females; # females pregnant per # females mated)
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 18,1433,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 600 mg/kg
SEX/DURATION : male 3 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
Reproductive - Fertility - male fertility index (e.g. # males impregnating
females per # males exposed to fertile nonpregnant females)
REFERENCE :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 41,411,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 3240 mg/kg
SEX/DURATION : male 9 week(s) pre-mating
female 2 week(s) pre-mating - 7 day(s) after
conception
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in
number of implants per female; total number of implants per corpora lutea)
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 18,1433,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 880 mg/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
Reproductive - Effects on Embryo or Fetus - fetal death
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 18,1433,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 1040 mg/kg
SEX/DURATION : female 17-21 day(s) after conception
lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition
Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4
per # born alive)
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 18,1433,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 300 mg/kg
SEX/DURATION : male 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - other effects on male
REFERENCE :
JOAND3 Journal of Andrology. (Lippincott/Harper, Journal Fulfillment Dept.,
2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1980-
Volume(issue)/page/year: 13,191,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 300 mg/kg
SEX/DURATION : male 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
REFERENCE :
JOAND3 Journal of Andrology. (Lippincott/Harper, Journal Fulfillment Dept.,
2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1980-
Volume(issue)/page/year: 13,191,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 520 mg/kg
SEX/DURATION : female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - other effects
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 18,1433,1984
** MUTATION DATA **
TYPE OF TEST : DNA inhibition
TEST SYSTEM : Human Lymphocyte
DOSE/DURATION : 10 mg/L
REFERENCE :
AMACCQ Antimicrobial Agents and Chemotherapy. (American Soc. for
Microbiology, 1913 I St., NW, Washington, DC 20006) V.1- 1972-
Volume(issue)/page/year: 24,478,1983
TYPE OF TEST : DNA inhibition
TEST SYSTEM : Human Cells - not otherwise specified
DOSE/DURATION : 1 umol/L
REFERENCE :
TUMOAB Tumori. (Casa Editrice Ambrosiana, Via G. Frua 6, 20146 Milan,
Italy) V.1- 1911- Volume(issue)/page/year: 77,385,1991
*** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA ***
NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA :
NOES - National Occupational Exposure Survey (1983)
NOES Hazard Code - X6059
No. of Facilities: 30 (estimated)
No. of Industries: 1
No. of Occupations: 3
No. of Employees: 1045 (estimated)
No. of Female Employees: 620 (estimated)
*** END OF RECORD ***