Benzotriazole ultraviolet stabilizers (BUVSs) are prominent chemicals widely used in industrial and consumer products to protect against ultraviolet radiation. They are becoming contaminants of emerging concern since their residues are frequently detected in multiple environmental matrices and their toxicological implications are increasingly reported. We herein investigated the antiandrogenic activities of eight BUVSs prior to and after human CYP3A4-mediated metabolic activation/deactivation by the two-hybrid recombinant human androgen receptor yeast bioassay and the in vitro metabolism assay. More potent antiandrogenic activity was observed for the metabolized UV-328 in comparison with UV-328 at 0.25 uM ((40.73 +/- 4.90)% vs. (17.12 +/- 3.00)%), showing a significant metabolic activation. In contrast, the metabolized UV-P at 0.25 uM resulted in a decreased antiandrogenic activity rate from (16.08 +/- 0.95)% to (6.91 +/- 2.64)%, indicating a metabolic deactivation. Three mono-hydroxylated (OH) and three di-OH metabolites of UV-328 were identified by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS), which were not reported previously. We further surmised that the hydroxylation of UV-328 occurs mainly at the alicyclic hydrocarbon atoms based on the in silico prediction of the lowest activation energies of hydrogen abstraction from C-H bond. Our results for the first time relate antiandrogenic activity to human CYP3A4 enzyme-mediated hydroxylated metabolites of BUVSs. The biotransformation through hydroxylation should be fully considered during the health risk assessment of structurally similar analogs of BUVSs and other emerging contaminants.
IDENTIFICATION AND USE: 2-(2H-Benzotriazol-2-yl)-4,6-di-tert-pentylphenol is used as a UV absorber in plastics applications. It is particularly recommended for polyolefins, polyurethanes, PVC, polyacrylate, epoxy, and elastomers. It offers strong intensity and broad UV absorption with a fairly sharp wavelength cutoff close to the visible region. HUMAN STUDIES: In vitro studies demonstrated antiandrogenic activity of human CYP3A4 enzyme-mediated hydroxylated metabolites. ANIMAL STUDIES: Rats were administered 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol via oral gavage at doses of 1392, 1800, 2325 mg/kg test-substance-basis for 14 days. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnea, curved position and ruffled fur. The animals recovered within 8 to 9 days. Beagle dogs were fed with a diet containing 0, 15, 30, 60, 120 and 240 mg/kg body weight for 3 months. One male from the high dose group died on the 8th week of treatment. Toxicity was more pronounced in the males than in the females. Body weight loss and depression of food consumption occurred in the high dose group. Hematological analysis revealed signs of anemia at the two highest dose groups. The data from blood chemistry revealed slight increased bilirubin, GTP, GOT and alkaline phosphatase activity in the serum. There were increased liver weights associated with severe liver damage including icterus (jaundice) in a few dogs in the 120 and 240 mg/kg groups. In rats fed for 90 days, hematological analysis revealed a treatment-related decrease of hemoglobin content and packed cell volume in males at 200 ppm and above. In females, this effect was less pronounced. The data from clinical chemistry revealed an increase of glucose-6-phosphatase at lower dose groups with a steady-state level at about 200 ppm. The liver, kidney, spleen and testes weights were increased. There were also some hints for increased thyroid weights in the higher dose groups. The liver was identified as the main target organ in rats. The chemical tested negative for mutagenic effects in Salmonella typhimurium strains: TA 98, TA 100, TA 1535 and TA 1537 with or without metabolic activation. ECOTOXICITY STUDIES: Daphnia magna growth, reproduction, and gene transcription were not impacted by 21-d exposure. In the algae, results showed increased ROS production in response to the chemical exposure. The transcription of superoxide dismutase (SOD), catalase (CAT), and ascorbic peroxidase (APX) was also regulated in the green algae, most likely as a result of ROS production and lipid peroxidation.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
职业性肝毒素 - 第二性肝毒素:在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。
Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Compounds of the formulae (I) or (II)
wherein
X is
A is O, S, NR
5
or CR
16
R
17
;
R
1
is for example hydrogen or C
1
-C
20
alkyl
R
2
is for example hydrogen, C
1
-C
20
alkyl or C
6
-C
20
aryl
R
5
for example is C
1
-C
20
alkyl;
R
7
, R
8
, R
9
, R
10
and R
11
for example independently of each other are hydrogen. C
1
-C
20
alkyl, halogen, CN or NO
2
;
Ar
1
is for example unsubstituted or substituted C
6
-C
20
aryl, C
3
-C
20
heteroaryl, C
6
-C
20
aroyl, C
3
-C
20
heteroarylcarbonyl or
or Ar
1
is
Ar
2
is for example phenylene,
all of which are unsubstituted or substituted
M is for example unsubstituted or substituted C
1
-C
20
alkylene
Y is a direct bond, O, S, NR
5
or CO;
Z
1
is for example O or S; Z
2
is a direct bond, O, S or NR
5
; and
Q is CO or a direct bond.
公式(I)或(II)的化合物
其中
X是
A是O, S, NR
5
或CR
16
R
17
;
R
1
例如是氢或C
1
-C
20
烷基
R
2
例如是氢, C
1
-C
20
烷基或C
6
-C
20
芳基
R
5
例如是C
1
-C
20
烷基;
R
7
, R
8
, R
9
, R
10
和R
11
例如彼此独立是氢. C
1
-C
20
烷基, 卤素, CN或NO
2
;
Ar
1
例如是不取代或取代的C
6
-C
20
芳基, C
3
-C
20
杂芳基, C
6
-C
20
芳酰基, C
3
-C
20
杂芳基甲酰基或
或Ar
1
是
Ar
2
例如是苯基,
所有这些都不取代或取代
M例如是不取代或取代的C
1
-C
20
亚烷基
Y是直接键, O, S, NR
5
或CO;
Z
1
例如是O或S; Z
2
是直接键, O, S或NR
5
; 和
Q是CO或直接键。
Heterocyclic Compound
申请人:Amasaki Ichiro
公开号:US20100004439A1
公开(公告)日:2010-01-07
A compound represented by the following Formula (1):
wherein, Het
1
represents a bivalent five- or six-membered aromatic heterocyclic residue and may further be substituted; X
a
to X
d
each independently represent a heteroatom and may further be substituted; Y
a
to Y
f
each independently represent a heteroatom or a carbon atom and may further be substituted; the ring bound to Het
1
may have a double bond at any position
Method for the preparation of aromatic chloroformates
申请人:Davis Charles Gary
公开号:US20060293535A1
公开(公告)日:2006-12-28
A method for preparing an aromatic chloroformate comprising, introducing a mixture of at least one aromatic hydroxyl compound, phosgene, at least one solvent, and at least one organic base into a flow reactor to obtain a unidirectionally flowing reaction mixture. The unidirectionally flowing reaction mixture is maintained at a temperature between about 0° C. and about 60° C. to produce a single product stream comprising an aromatic chloroformate.
[EN] STERICALLY HINDERED AMINE STABILIZERS<br/>[FR] STABILISANTS D'AMINES À ENCOMBREMENT STÉRIQUE
申请人:BASF SE
公开号:WO2010142572A1
公开(公告)日:2010-12-16
The instant invention pertains to hindered amine compounds having at least two nitrogen atoms with different basicity. One part is substituted on the N-atom by alkoxy moieties and the other part is substituted on the N-atom by a hydroxy-alkyl moiety. These materials are particularly effective in stabilizing polymers, especially thermoplastic polyolefins, against the deleterious effects of oxidative, thermal and actinic radiation. The compounds are also particularly effective in stabilizing acid catalyzed and ambient cured coatings systems.
4-Formyl amino-n-methylpiperidine derivatives, the use thereof as stabilisers and organic material stabilised therewith
申请人:——
公开号:US20030083406A1
公开(公告)日:2003-05-01
The present invention relates to 4-formylamino-N-methylpiperidine derivatives of the formula (I)
1
where the variables are as defined in the Description, to a process for preparing these piperidine derivatives, to the use of these piperidine derivatives of the invention, or prepared according to the invention, for stabilizing organic material, in particular for stabilizing plastics or coating materials, and also to the use of these piperidine derivatives of the invention, or prepared according to the invention, as light stabilizers or stabilizers for wood surfaces.
The present invention further relates to stabilized organic material which comprises these piperidine derivatives of the invention or prepared according to the invention.