L-thyroxine

Modify Date: 2024-01-04 14:50:54

L-thyroxine Structure
L-thyroxine structure
Common Name L-thyroxine
CAS Number 51-48-9 Molecular Weight 776.870
Density 2.6±0.1 g/cm3 Boiling Point 576.3±50.0 °C at 760 mmHg
Molecular Formula C15H11I4NO4 Melting Point 235 °C
MSDS Chinese USA Flash Point 302.3±30.1 °C
Symbol GHS02 GHS06 GHS08
GHS02, GHS06, GHS08
Signal Word Danger

 Use of L-thyroxine


L-Thyroxine (Levothyroxine; T4) is a synthetic hormone in the treatment of hypothyroidism. DIO enzymes convert biologically active thyroid hormone (Triiodothyronine,T3) from L-Thyroxine (T4).

 Names

Name L-thyroxine
Synonym More Synonyms

 L-thyroxine Biological Activity

Description L-Thyroxine (Levothyroxine; T4) is a synthetic hormone in the treatment of hypothyroidism. DIO enzymes convert biologically active thyroid hormone (Triiodothyronine,T3) from L-Thyroxine (T4).
Related Catalog
Target

Human Endogenous Metabolite

In Vivo Deiodinases (DIOs), which catalyse the conversion of thyroxine (pro-hormone) to the active thyroid hormone, are associated with thyroid stimulating hormone (TSH) levels. DIO1 and DIO2 catalyze activation of thyroid hormone secretion in contrast to DIO3 playing role inactivation of the secretion. Activities of DIO1 and DIO2 play pivotal role in the negative feedback regulation of pituitary TSH secretion[1]. L-Thyroxine (T4) and Triiodothyronine (T3) hormones are known to modulate the expression of ionic channels, pumps and regulatory contractile proteins. Moreover, thyroid hormones have been shown to influence calcium homeostasis and flux responsible for excitation and contractility, with L-Thyroxine and Triiodothyronine modulating its pharmacological control and secretion. In rats fed 12 weeks with the iodine-free diet, a significant decrease in the levels of both Triiodothyronine and L-Thyroxine is observed when compared to the control group fed with standard diet (p<0.001). In the group treated with low doses of L-Thyroxine, an increase in L-Thyroxine levels is observed (p=0.02) while Triiodothyronine levels remain virtually similar to the control group (p=0.19). Rats treated with high doses of L-Thyroxine display a significant increase in both Triiodothyronine and L-Thyroxine circulating concentrations compared to the non-treated hypothyroid group (p<0.001 and p=0.004, respectively) and a significant increase in L-Thyroxine levels when compared to the control values (p=0.03)[2].
Animal Admin Rats[2] Sprague-Dawley female rats (N=22) are used. Non-pregnant rats are divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low doses of L-Thyroxine (20 μg/kg/day) and 4) with high doses of L-Thyroxine (100 μg/kg/day). Control rats (group 1) are fed with standard diet, while the intervention rats are fed with iodine-free diet for 12 weeks to induce hypothyroidism (groups 2-4) which is continued for four more weeks to allow screening of hypothyroid status and L-Thyroxine-treatment. Food and water (iodine-free diet) are available ad libitum. The hypothyroid group treated with low (group 3) or high doses of L-Thyroxine (group 4) are injected intraperitoneally every 24 h with respectively 20 μg/kg/day and 100 μg/kg/day. Blood samples are collected for thyroid function screening at week 12 and 16 following the initiation of either the control or iodine-free diet. Hysterectomy is performed under general anesthesia (isoflurane 2%) at the end of the treatment and the two uterine horns are placed in physiological Krebs' solution until isometric tension measurements within no more than 1 h.
References

[1]. Arici M, et al. Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients. Endocr J. 2018 Jan 11.

[2]. Corriveau S, et al. Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animalmodel. J Clin Transl Endocrinol. 2015 Sep 9;2(4):144-149.

 Chemical & Physical Properties

Density 2.6±0.1 g/cm3
Boiling Point 576.3±50.0 °C at 760 mmHg
Melting Point 235 °C
Molecular Formula C15H11I4NO4
Molecular Weight 776.870
Flash Point 302.3±30.1 °C
Exact Mass 776.686646
PSA 92.78000
LogP 5.93
Vapour Pressure 0.0±1.7 mmHg at 25°C
Index of Refraction 1.795
Storage condition 2~8°C
Water Solubility insoluble

 MSDS

Name: L-Thyroxine 99% Material Safety Data Sheet
Synonym: None Known
CAS: 51-48-9
Section 1 - Chemical Product MSDS Name:L-Thyroxine 99% Material Safety Data Sheet
Synonym:None Known

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS
CAS# Chemical Name content EINECS#
51-48-9 L-Thyroxine 99% 200-101-1
Hazard Symbols: XN
Risk Phrases: 20/21/22

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful by inhalation, in contact with skin and if swallowed.The toxicological properties of this material have not been fully investigated.Light sensitive.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid if irritation develops or persists. Wash clothing before reuse. Flush skin with plenty of soap and water.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. Runoff from fire control or dilution water may cause pollution.
Extinguishing Media:
In case of fire, use water, dry chemical, chemical foam, or alcohol-resistant foam. Use agent most appropriate to extinguish fire.

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Store protected from light.
Storage:
Keep container closed when not in use. Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. Hormones and antibiotics room. Store protected from light.

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Good general ventilation should be sufficient to control airborne levels. Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower.
Exposure Limits CAS# 51-48-9: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to minimize contact with skin.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: cream
Odor: none reported
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: Decomposes
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: Not available.
Solubility in water: Insoluble in water
Specific Gravity/Density: Not available.
Molecular Formula: C15H11I4NO4
Molecular Weight: 776.6993

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, light, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents, strong bases.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide, nitrogen, hydrogen iodide.
Hazardous Polymerization: Has not been reported.

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 51-48-9: YP2833500 LD50/LC50:
Not available.
Carcinogenicity:
L-Thyroxine - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

Section 12 - ECOLOGICAL INFORMATION


Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XN
Risk Phrases:
R 20/21/22 Harmful by inhalation, in contact with
skin and if swallowed.
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 51-48-9: 1
Canada
CAS# 51-48-9 is listed on Canada's DSL List.
CAS# 51-48-9 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 51-48-9 is listed on the TSCA inventory.


SECTION 16 - ADDITIONAL INFORMATION
N/A

 Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
YP2833500
CHEMICAL NAME :
L-Tyrosine, O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-
CAS REGISTRY NUMBER :
51-48-9
BEILSTEIN REFERENCE NO. :
2228515
LAST UPDATED :
199709
DATA ITEMS CITED :
15
MOLECULAR FORMULA :
C15-H11-I4-N-O4
MOLECULAR WEIGHT :
776.87
WISWESSER LINE NOTATION :
QVYZ1R CI EI DOR DQ CI EI

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
63 ug/kg
TOXIC EFFECTS :
Behavioral - hallucinations, distorted perceptions Cardiac - pulse rate increase, without fall in BP
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
400 ug/kg/2D-I
TOXIC EFFECTS :
Behavioral - coma Cardiac - arrhythmias (including changes in conduction)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
2 mg/kg/10D-I
TOXIC EFFECTS :
Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - monoamine oxidase Biochemical - Metabolism (Intermediary) - effect on mitochondrial function
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
26250 ug/kg
SEX/DURATION :
female 1-21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - eye/ear
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1400 ug/kg
SEX/DURATION :
female 16-22 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - biochemical and metabolic
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
410 mg/kg
SEX/DURATION :
female 3 week(s) pre-mating female 1-20 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
450 ug/kg
SEX/DURATION :
female 7-15 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
8160 ug/kg
SEX/DURATION :
female 7 day(s) pre-mating - 5 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - postpartum
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
600 ug/kg
SEX/DURATION :
female 19-21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - urogenital system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
12 mg/kg
SEX/DURATION :
male 6 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
12 mg/kg
SEX/DURATION :
female 9-11 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

MUTATION DATA

TEST SYSTEM :
Rodent - rat
DOSE/DURATION :
6250 ug/kg/2D (Continuous)
REFERENCE :
BEXBAN Bulletin of Experimental Biology and Medicine (English Translation). Translation of BEBMAE. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) V.41- 1956- Volume(issue)/page/year: 72,942,1971 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - M0234 No. of Facilities: 68 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 2770 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - M0234 No. of Facilities: 717 (estimated) No. of Industries: 4 No. of Occupations: 9 No. of Employees: 10666 (estimated) No. of Female Employees: 7298 (estimated)

 Safety Information

Symbol GHS02 GHS06 GHS08
GHS02, GHS06, GHS08
Signal Word Danger
Hazard Statements H225-H301 + H311 + H331-H370
Precautionary Statements P210-P260-P280-P301 + P310 + P330-P302 + P352 + P312-P370 + P378
Personal Protective Equipment Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
Hazard Codes Xn:Harmful
Risk Phrases R20/21/22
Safety Phrases S22-S24/25
RIDADR 2811.0
WGK Germany 3
RTECS YP2833500
Hazard Class 6.1
HS Code 2942000000

 Synthetic Route

 Customs

HS Code 2922509090
Summary 2922509090. other amino-alcohol-phenols, amino-acid-phenols and other amino-compounds with oxygen function. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

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 Synonyms

Thyroxine (VAN)
b-((3,5-Diiodo-4-hydroxyphenoxy)-3,5-diiodophenyl)alanine
Thyroxine, L- (8CI)
EINECS 200-101-1
(-)-3-[4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]alanine
3,3’,5,5‘’-Tetraiodo-L-thyronine
O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine
3-[4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-L-alanine
Thyroxine
L-3,5,3',5'-Tetraiodothyronine
thyroxine-binding globulin
(-)-Thyroxine
Thryroxine, l-
thyroxin
T4
L-Thyroxine
Tetraiodothyronine
THX
L-Tyrosine, O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-
transthyretin
L-Thyroxin
Thyroxine, L-
Thyrax
l-t4
Levothyroxine
3,5,3',5'-Tetraiodothyronine
O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosine
4-14-00-02373 (Beilstein Handbook Reference)
thyroxinal
L-thyroxine zwitterion
(2S)-2-Amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Henning
MFCD00002596
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