水杨酸钠

Sodium Salicylate 抑制 COX-2 活性,抑制作用与转录因子 (NF-κB) 激活无关。

信号通路 >> 自噬 >> 自噬

研究领域 >> 炎症/免疫

COX-2

Autophagy

水杨酸钠是一种有效的COX-2活性抑制剂,其浓度远低于抑制NF-κB(20 mg/mL)活化所需的浓度。当与白细胞介素1β一起加入24小时时,水杨酸钠抑制前列腺素E2释放,IC50值为5μg/ mL,这种作用不依赖于NF-κB活化或COX-2转录或翻译。在0,1或10μM外源花生四烯酸存在下,急性(30分钟)水杨酸钠也引起浓度依赖性的COX-2活性抑制。相反,当外源花生四烯酸增加至30μM时,水杨酸钠是一种非常弱的COX-2活性抑制剂,IC50>100μg/ mL。当与IL-1β一起加入24小时时,水杨酸钠引起PGE 2释放的浓度依赖性抑制,表观IC 50值为约5μg/ mL。在暴露30分钟后测试水杨酸钠直接抑制A549细胞中COX-2活性的能力,然后加入不同浓度的外源花生四烯酸(1,10和30μM)。在没有添加花生四烯酸的情况下或在1或10μM外源底物存在下,水杨酸钠引起COX-2活性的浓度依赖性抑制,表观IC 50值为约5μg/ mL。然而,当使用30μM花生四烯酸进行相同的实验时,水杨酸钠是COX-2活性的无效抑制剂,表观IC50值大于100μg/ mL,并且实现最大抑制小于50％[ 1]。

在C57Bl/6 DIO小鼠中,水杨酸盐降低空腹和餐后血浆葡萄糖水平。此外,在C57Bl/6DIO小鼠中水杨酸盐处理后存在降低血浆甘油三酯水平的趋势(P = 0.059)。水杨酸盐显着降低C57Bl/6 DIO小鼠网膜脂肪组织中的11β-HSD1 mRNA,其在肠系膜脂肪中具有相似的趋势(P = 0.057)。在C57Bl/6 DIO小鼠的肠系膜脂肪中,水杨酸盐还降低了11β-HSD1酶活性[2]。

将人纯化的COX-2和辅因子谷胱甘肽（5mM），肾上腺素（5mM）和血红素（1μM）溶解于50mM Tris缓冲液（pH7.5）中。首先将血红素溶于100mM的1M NaOH浓缩原液中，然后在Tris缓冲液中进一步稀释。酶反应在96孔板的各孔中进行，最终反应体积为200μL。向板中加入不同浓度的水杨酸钠，然后加入10单位的酶（180μL）。将板在37°温育30分钟，然后再加入花生四烯酸（10nM至30μM）15分钟。通过将板加热至100℃持续5分钟来终止反应。然后将96孔板以10,000×g离心10分钟，取出适当的样品并加入放射免疫测定[1]。

为了评估水杨酸钠在诱导后对COX-2活性的直接影响，首先用IL-1β处理A549细胞24小时，并用含有不同浓度的水杨酸钠的DMEM替换培养基（10,100和1000μg/ mL）。将细胞在37℃下孵育30分钟。然后加入花生四烯酸（1-30μM）15分钟，取出培养基用于测量PGE2 [1]。

小鼠[2]成年雄性C57Bl / 6小鼠在12周龄。饮食诱导的肥胖C57Bl / 6小鼠（C57B1 / 6DIO）在治疗前给予10周的高脂肪饮食（58％脂肪，12％蔗糖）。在到达（C57Bl / 6 Lean）后1周，高脂肪喂养10周后（C57Bl / 6 DIO）或达到目标体重后给予水杨酸钠（120mg / kg /天）或蒸馏水（载体） （HSD1KO-DIO）通过渗透性微型泵在肩胛骨之间皮下植入4周至n = 8组。

[1]. Mitchell JA, et al. Sodium salicylate inhibits cyclo-oxygenase-2 activity independently of transcription factor (nuclear factor kappaB) activation: role of arachidonic acid. Mol Pharmacol. 1997 Jun;51(6):907-12.

[2]. Nixon M, et al. Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization. Diabetes. 2012 Apr;61(4):790-6.

对乙酰氨基苯酚 | 阿司匹林 | 非洲豆蔻醇 | 人参皂苷Rg3 | 人参皂苷CK | 黄腐酚 | 布洛芬 | 双氯芬酸 | NS-398(COX-2抑制剂) | 美洛昔康 | 氟芬那酸 | 表儿茶素(EC) | 水杨酸 | 酮洛芬 | 萘普生

MOLECULAR FORMULA :

C7-H5-O3.Na

MOLECULAR WEIGHT :

160.11

WISWESSER LINE NOTATION :

QVR BQ &-NA-

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

700 mg/kg

TOXIC EFFECTS :

Behavioral - excitement Behavioral - muscle contraction or spasticity Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

1400 mg/kg

TOXIC EFFECTS :

Behavioral - toxic psychosis Lungs, Thorax, or Respiration - respiratory stimulation Skin and Appendages - sweating

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Multiple routes

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

2970 mg/kg/13D

TOXIC EFFECTS :

Behavioral - excitement Gastrointestinal - nausea or vomiting

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

930 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - muscle contraction or spasticity

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

542 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

540 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

550 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

560 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

760 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

450 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

990 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

562 mg/kg

TOXIC EFFECTS :

Behavioral - analgesia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

1700 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

415 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

900 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

800 mg/kg

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction) Behavioral - excitement Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Amphibian - frog

DOSE/DURATION :

250 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2100 mg/kg/7D-C

TOXIC EFFECTS :

Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

6600 mg/kg/11D-I

TOXIC EFFECTS :

Liver - other changes Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

16350 mg/kg/15W-I

TOXIC EFFECTS :

Behavioral - muscle weakness Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

18200 mg/kg/13W-C

TOXIC EFFECTS :

Liver - other changes Kidney, Ureter, Bladder - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3360 mg/kg/14D-I

TOXIC EFFECTS :

Behavioral - fluid intake Kidney, Ureter, Bladder - urine volume increased Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

3900 mg/kg/2W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

40 mg/kg

SEX/DURATION :

female 20-21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

250 mg/kg

SEX/DURATION :

female 9 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 - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

250 mg/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

25 mg/kg

SEX/DURATION :

female 20-21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

375 mg/kg

SEX/DURATION :

female 8-10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

500 mg/kg

SEX/DURATION :

female 8 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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

849 mg/kg

SEX/DURATION :

female 9-11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

150 mg/kg

SEX/DURATION :

female 12-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

300 mg/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

50 mg/kg

SEX/DURATION :

female 21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

400 mg/kg

SEX/DURATION :

female 10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

300 mg/kg

SEX/DURATION :

female 10 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 :

Intravenous

DOSE :

600 mg/kg

SEX/DURATION :

female 6-13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

400 mg/kg

SEX/DURATION :

female 10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

400 mg/kg

SEX/DURATION :

female 10 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 - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

665 mg/kg

SEX/DURATION :

female 17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Effects on Embryo or Fetus - other effects to embryo Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4 gm/kg

SEX/DURATION :

female 8-12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2 gm/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1500 mg/kg

SEX/DURATION :

female 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

8 gm/kg

SEX/DURATION :

female 8-12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

400 mg/kg

SEX/DURATION :

female 12 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 - cardiovascular (circulatory) system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

400 mg/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

500 mg/kg

SEX/DURATION :

female 17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

500 mg/kg

SEX/DURATION :

female 17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1100 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

125 mg/kg

SEX/DURATION :

female 18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

250 mg/kg

SEX/DURATION :

female 18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

400 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

125 mg/kg

SEX/DURATION :

female 18 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 :

DNA damage

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TEST SYSTEM :

Rodent - mouse

DOSE/DURATION :

350 mg/kg

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 370,1,1996 *** REVIEWS *** TOXICOLOGY REVIEW PEDIAU Pediatrics. (American Academy of Pediatrics, P.O. Box 1034, Evanston, IL 60204) V.1- 1948- Volume(issue)/page/year: 54,342,1974 TOXICOLOGY REVIEW ARVPAX Annual Review of Pharmacology. (Palo Alto, CA) V.1-15, 1961-75. For publisher information, see ARPTDI. Volume(issue)/page/year: 5,447,1965 TOXICOLOGY REVIEW AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New York, NY 10022) V.1- 1946- Volume(issue)/page/year: 38,409,1965 TOXICOLOGY REVIEW ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ. Volume(issue)/page/year: 4,263,1966 TOXICOLOGY REVIEW 85DJA5 "Malformations Congenitales des Mammiferes," Tuchmann-Duplessis, H., Paris, Masson et Cie, 1971 Volume(issue)/page/year: -,171,1971 TOXICOLOGY REVIEW APSQA7 Acta Paediatrica Scandinavica, Supplement. (Almqvist & Wiksell International, POB 4627, S-11691 Stockholm, Sweden) No. 158-379 1965-91 Volume(issue)/page/year: (211),24,1971 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 84407 No. of Facilities: 1892 (estimated) No. of Industries: 6 No. of Occupations: 16 No. of Employees: 16641 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 84407 No. of Facilities: 2056 (estimated) No. of Industries: 9 No. of Occupations: 18 No. of Employees: 29395 (estimated) No. of Female Employees: 19141 (estimated)