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33286-22-5

33286-22-5 structure
33286-22-5 structure

Name diltiazem hydrochloride
Synonyms Adizem
masdil
1,5-Benzothiazepin-4(5H)-one, 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-, (2S,3S)-, hydrochloride (1:1)
MFCD00069252
Kardil
Diltiazem hydrochloride s
Dilthiazem hydrochloride
(2S,3S)-(+)-cis-3-Acetoxy-5-(2-dimethylaminoethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one hydrochloride
(2S,3S)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate hydrochloride
(+)-cis-Diltiazem Hydrochloride
Cohlen
Cormax
Zilde
Diltiazem HCl
angiotrofin
EINECS 251-443-3
(2S,3S)-5-[2-(Dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-ylacetathydrochlorid
dilzem
bruzem
Diltiazem (hydrochloride)
(+)-cis-3-(Acetyloxy)-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one Monohydrochloride
Dodexen A.P.
1,5-benzothiazepin-4(5H)-one, 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-, (2S,3S)-, monohydrochloride
Diltiazem d-cis-form hydrochloride
Presokin A. P.
acétate de (2S,3S)-5-[2-(diméthylamino)éthyl]-2-(4-méthoxyphényl)-4-oxo-2,3,4,5-tétrahydro-1,5-benzothiazépin-3-yle chlorhydrate
Tiazac
(2S,3S)-5-[2-(Dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate hydrochloride (1:1)
Diltiazem hydrochloride
Zilden
Description Diltiazem hydrochloride is a Ca2+ influx inhibitor (slow channel blocker or calcium antagonist).
Related Catalog
In Vitro Benzothiazepine Ca2+ antagonist diltiazem hydrochloride interacts with transmembrane segments IIIS6 and IVS6 in the α1 subunit of L-type Ca2+ channels[1]. Diltiazem causes a dose-dependent inhibiton of contractions as well as Ca2+ influx stimulated by alpha adrenoceptor activation and high-K+ depolarization. Diltiazem is roughly equally potent in inhibiting contractions induced by high-K+ and a low concentration of norepinephrine (NE)[2]. Diltiazem also inhibits the Na-dependent Ca-efflux from heart mitochondria. Both the (+)-optical isomers of the cis- and trans-forms of diltiazem inhibit Na-Ca exchange activity with comparable potency (IC50 of 10-20 μM)[3].
In Vivo Diltiazem produces a noncompetitive inhibition of Ca2+-induced contractions of depolarized rabbit aorta. Furthermore, there is a lack of parallelism between the smooth muscle effects of removal of [Ca2+]ex and of addition of diltiazem[2]. Diltiazem improves the cardiac microcirculation and function in an experimental model of hyperthyroidism in rats. The treatment of hyperthyroid rats with losartan diltiazem (4.7±0.7%; P < 0.001) significantly reduces the percentage of fibrosis areas in the left ventricle [4]. In conscious spontaneously hypertensive rats (SHR), diltiazem dose-dependently decreases the blood pressure and increases the heart rate after intravenous administration (0.03--1 mg/kg). Oral administration of diltiazem (100 mg/kg) also reduces the blood pressure of SHR[5].
References

[1]. Kraus RL, et al. Molecular mechanism of diltiazem interaction with L-type Ca2+ channels. J Biol Chem. 1998 Oct 16;273(42):27205-12.

[2]. van Breemen C, et al. The mechanism of inhibitory action of diltiazem on vascular smooth muscle contractility. J Pharmacol Exp Ther. 1981 Aug;218(2):459-63.

[3]. Chiesi M, et al. Stereospecific action of diltiazem on the mitochondrial Na-Ca exchange system and on sarcolemmal Ca-channels. Biochem Pharmacol. 1987 Sep 1;36(17):2735-40.

[4]. Freitas F, et al. Cardiac microvascular rarefaction in hyperthyroid rats is reversed by losartan, diltiazem, and propranolol. Fundam Clin Pharmacol. 2015 Feb;29(1):31-40.

[5]. Sato M, et al. Hypotensive effects of diltiazem hydrochloride in the normotensive, spontaneously hypertensive and renal hypertensive rats (author's transl). Nihon Yakurigaku Zasshi. 1979 Mar;75(2):99-106.

Density 1.26g/cm3
Boiling Point 594.4ºC at 760mmHg
Melting Point 212-214 °C
Molecular Formula C22H27ClN2O4S
Molecular Weight 450.979
Flash Point 313.3ºC
Exact Mass 450.138000
PSA 84.38000
LogP 4.23550
Index of Refraction 118 ° (C=1, H2O)
Storage condition 2-8°C
Water Solubility soluble

CHEMICAL IDENTIFICATION

RTECS NUMBER :
DL0310000
CHEMICAL NAME :
1,5-Benzothiazepin-4(5H)-one, 2,3-dihydro-3-(acetyloxy)-5-(2-(dimethylamino)ethyl)- 2-(4- methoxyphenyl)-, monohydrochloride, cis-(+)-
CAS REGISTRY NUMBER :
33286-22-5
LAST UPDATED :
199607
DATA ITEMS CITED :
37
MOLECULAR FORMULA :
C22-H26-N2-O4-S.Cl-H
MOLECULAR WEIGHT :
451.02
WISWESSER LINE NOTATION :
T67 GNV KS&TJ G2N1&1 IOV1 JR DO1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
21 mg/kg
TOXIC EFFECTS :
Cardiac - cardiomyopathy including infarction Cardiac - pulse rate Vascular - BP lowering not characterized in autonomic section
REFERENCE :
PGMJAO Postgraduate Medical Journal. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1925- Volume(issue)/page/year: 69,474,1993
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
3429 ug/kg/2D-I
TOXIC EFFECTS :
Skin and Appendages - dermatitis, other (after systemic exposure)
REFERENCE :
LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 341,967,1993
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
8400 ug/kg
TOXIC EFFECTS :
Cardiac - pulse rate Vascular - BP lowering not characterized in autonomic section
REFERENCE :
AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 22,196,1993
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
18 mg/kg
TOXIC EFFECTS :
Cardiac - cardiomyopathy including infarction Cardiac - pulse rate Vascular - BP lowering not characterized in autonomic section
REFERENCE :
JTCTDW Journal of Toxicology, Clinical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.19- 1982- Volume(issue)/page/year: 29,45,1991
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
120 mg/kg
TOXIC EFFECTS :
Cardiac - cardiomyopathy including infarction
REFERENCE :
HETOEA Human & Experimental Toxicology. (Macmillan Press Ltd., Brunel Road, Houndmills, Basingstoke, Hampshire, RG21 2XS, UK) V.9- 1990- Volume(issue)/page/year: 13,161,1994
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
19 mg/kg
TOXIC EFFECTS :
Skin and Appendages - dermatitis, other (after systemic exposure)
REFERENCE :
PGMJAO Postgraduate Medical Journal. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1925- Volume(issue)/page/year: 64,467,1988
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
36 mg/kg/13D-I
TOXIC EFFECTS :
Liver - hepatitis, fibrous (cirrhosis, post-necrotic scarring)
REFERENCE :
GASTAB Gastroenterology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1943- Volume(issue)/page/year: 88,1260,1985
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
18 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity) Vascular - BP lowering not characterized in autonomic section Skin and Appendages - sweating
REFERENCE :
JTCTDW Journal of Toxicology, Clinical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.19- 1982- Volume(issue)/page/year: 29,45,1991
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
7200 ug/kg/2D-I
TOXIC EFFECTS :
Behavioral - hallucinations, distorted perceptions Behavioral - toxic psychosis
REFERENCE :
JRSMD9 Journal of the Royal Society of Medicine. (Oxford Univ. Press, Walton St., Oxford OX2 6DP, UK) V.71- 1978- Volume(issue)/page/year: 81,296,1988
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
7200 ug/kg
TOXIC EFFECTS :
Behavioral - hallucinations, distorted perceptions Behavioral - toxic psychosis
REFERENCE :
JRSMD9 Journal of the Royal Society of Medicine. (Oxford Univ. Press, Walton St., Oxford OX2 6DP, UK) V.71- 1978- Volume(issue)/page/year: 81,296,1988
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
560 mg/kg
TOXIC EFFECTS :
Behavioral - antipsychotic
REFERENCE :
JJPAAZ Japanese Journal of Pharmacology. (Japanese Pharmacological Soc., c/o Dept. of Pharmacology, Faculty of Medicine, Kyoto Univ., Sakyo-ku, Kyoto 606, Japan) V.1- 1951- Volume(issue)/page/year: 22,467,1972
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
520 mg/kg
TOXIC EFFECTS :
Behavioral - antipsychotic
REFERENCE :
JJPAAZ Japanese Journal of Pharmacology. (Japanese Pharmacological Soc., c/o Dept. of Pharmacology, Faculty of Medicine, Kyoto Univ., Sakyo-ku, Kyoto 606, Japan) V.1- 1951- Volume(issue)/page/year: 22,467,1972
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
38 mg/kg
TOXIC EFFECTS :
Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Behavioral - tetany
REFERENCE :
JMGZAI Japan Medical Gazette. (Tokyo, Japan) V.1-18(?), 1964-81. Discontinued. Volume(issue)/page/year: 11(1),12,1974
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
508 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 33,2192,1990
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
177 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 29,820,1986
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
260 mg/kg
TOXIC EFFECTS :
Behavioral - antipsychotic
REFERENCE :
JJPAAZ Japanese Journal of Pharmacology. (Japanese Pharmacological Soc., c/o Dept. of Pharmacology, Faculty of Medicine, Kyoto Univ., Sakyo-ku, Kyoto 606, Japan) V.1- 1951- Volume(issue)/page/year: 22,467,1972
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
58 mg/kg
TOXIC EFFECTS :
Behavioral - antipsychotic
REFERENCE :
JJPAAZ Japanese Journal of Pharmacology. (Japanese Pharmacological Soc., c/o Dept. of Pharmacology, Faculty of Medicine, Kyoto Univ., Sakyo-ku, Kyoto 606, Japan) V.1- 1951- Volume(issue)/page/year: 22,467,1972
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
40 mg/kg
TOXIC EFFECTS :
Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting
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: 21,4843,1987 ** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
45500 mg/kg/26W-C
TOXIC EFFECTS :
Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases Related to Chronic Data - death
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,757,1974
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
1638 mg/kg/13W-I
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity) Endocrine - changes in adrenal weight Skin and Appendages - dermatitis, other (after systemic exposure)
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: 21,4851,1987 ** REPRODUCTIVE DATA **
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1200 mg/kg
SEX/DURATION :
female 9-14 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition 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: 8,3401,1974
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
60 mg/kg
SEX/DURATION :
female 9-14 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - live birth index (measured after 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: 8,3401,1974
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
700 mg/kg
SEX/DURATION :
female 15-21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)
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: 8,3401,1974
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
600 mg/kg
SEX/DURATION :
female 11 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)
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: 8,3401,1974
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
480 mg/kg
SEX/DURATION :
female 9-14 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities
REFERENCE :
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine, Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14- 1936- Volume(issue)/page/year: 52,103,1975
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
80 mg/kg
SEX/DURATION :
female 13 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine, Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14- 1936- Volume(issue)/page/year: 52,103,1975
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
DOSE :
130 mg/kg
SEX/DURATION :
female 17-21 day(s) after conception lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)
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: 21,4869,1987
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
DOSE :
378 mg/kg
SEX/DURATION :
female 14 day(s) pre-mating female 1-7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
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: 21,4857,1987
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
60 mg/kg
SEX/DURATION :
female 7-12 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: 8,3401,1974
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
25 mg/kg
SEX/DURATION :
female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)
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: 8,3401,1974
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
100 mg/kg
SEX/DURATION :
female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - sex ratio
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: 8,3401,1974
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
25 mg/kg
SEX/DURATION :
female 10 day(s) after conception
TOXIC EFFECTS :
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: 8,3401,1974
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
12500 ug/kg
SEX/DURATION :
female 11 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)
REFERENCE :
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine, Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14- 1936- Volume(issue)/page/year: 52,103,1975
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
25 mg/kg
SEX/DURATION :
female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine, Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14- 1936- Volume(issue)/page/year: 52,103,1975
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
50 mg/kg
SEX/DURATION :
female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)
REFERENCE :
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine, Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14- 1936- Volume(issue)/page/year: 52,103,1975
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
50 mg/kg
SEX/DURATION :
female 13 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - other developmental abnormalities
REFERENCE :
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine, Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14- 1936- Volume(issue)/page/year: 52,103,1975
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
125 mg/kg
SEX/DURATION :
female 7-16 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine, Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14- 1936- Volume(issue)/page/year: 52,103,1975
Symbol GHS02 GHS07
GHS02, GHS07
Signal Word Danger
Hazard Statements H225-H302 + H312 + H332-H319
Precautionary Statements P210-P261-P302 + P352 + P312-P304 + P340 + P312-P337 + P313-P403 + P235
Personal Protective Equipment dust mask type N95 (US);Eyeshields;Gloves
Hazard Codes Xn:Harmful
Risk Phrases R22;R40
Safety Phrases S36-S45-S36/37
RIDADR 3249
WGK Germany 3
RTECS DL0310000
Packaging Group III
Hazard Class 6.1(b)
HS Code 2934999090
HS Code 2934999090
Summary 2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%