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Chemical Sampling Information (CSI)
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General Description

Synonyms: Amethopterin; 4-Amino-l0-methylfolic acid; 1-Glutamic acid, N-(4-(((2,4-diamino-6-pteridinyl)methyl)methylamino))benzoyl; Glutamic acid, N-(p-(((2,4-diamino-6-pteridinyl)methyl)methylamino)benzoyl)-, L; Methopterin; Amethopterine; HDMTX; MTX; L-N-(p-(((2,4-diamino-6-pteridinyl)methyl)methylamino)benzoyl) Glutamic acid

OSHA IMIS Code Number: M106

Chemical Abstracts Service (CAS) Registry Number: 59-05-2

NIOSH Registry of Toxic Effects of Chemical Substances (RTECS) Identification Number: MA1225000

Chemical Description and Physical Properties:

bright yellow-orange, odorless, crystalline powder
molecular weight: 454.4
molecular formula: C20H22N8O5
melting point: 185-204°C (monohydrate)

Health Factors

Carcinogenic Classification:

International Agency for Research on Cancer (IARC): Group 3, not classifiable as to its carcinogenicity to humans [1 MB PDF, 454 pages]

Potential Symptoms: Nausea, vomiting, loss of appetite, weight loss; bloody diarrhea; sores inside the mouth; low white blood cell count; hair loss; skin rash; dry cough; liver and kidney damage

Health Effects: Reproductive hazard---Impaired fertility, Miscarriage, Teratogenesis (HE5); Immunosuppression (HE3)

Affected Organs: Blood, liver, kidneys, reproductive system


  1. OSHA does not have a PEL for methotrexate.
  2. One case report indicated allergic contact dermatitis in a worker at a methotrexate manufacturer, which was attributed to cross-sensitivity with a precursor to methotrexate synthesis, 2,4-diamino-6-chloromethylpteridine HCl.
  3. Except for rare cases of allergic contact dermatitis, adverse health effects of occupational exposure to methotrexate have not been reported.
  4. Health effects, if any, of the increased incidence of genetic damage markers reported for workers (with unknown exposure levels) at a methotrexate production facility in China remain to be elucidated.
  5. Teratogenic effects (craniofacial and digital anomalies, growth retardation) have been described in offspring of pregnant women receiving methotrexate for cancer treatment or in attempts to induce abortion.

Literature Basis:

  • Bawle, E.V., Conard, J.V. and Weiss, L.: Adult and two children with fetal methotrexate syndrome. Teratology 57(2): 51-55, 1998.
  • Dastychová, E.: Allergic contact dermatitis in methotrexate manufacture. Contact Dermatitis 48(4): 226-227, 2003.
  • Deng, H., et al.: Investigating genetic damage in workers occupationally exposed to methotrexate using three genetic end-points. Mutagenesis 20(5): 351-357, 2005.
  • Izzedine, H., Launay-Vacher, V. Karie, S., Caramella, C., de Person, F. and Deray, G.: Is low-dose methotrexate nephrotoxic? Case report and review of the literature. Clin. Nephrol. 64(4): 315-319, 2005.
  • Kalantzis, A., Marshman, Z., Falconer, D.T., Morgan, P.R. and Odell E.W.: Oral effects of low-dose methotrexate treatment. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 100(1): 52-62, 2005.
  • Lateef, O., Shakoor, N. and Balk, R.A.: Methotrexate pulmonary toxicity. Expert Opin. Drug Saf. 4(4): 723-730, 2005.
  • Pohanish, R.P. (editor): Methotrexate. In, Sittig's Handbook of Toxic and Hazardous Chemicals and Carcinogens, Fourth Ed., Vol. 2. Norwich, NY: Noyes Publications, William Andrew Publishing, 2002, pp. 1504-1505.
  • Sessink, P.J., Friemel, N.S., Anzion, R.B. and Bos, R.P.: Biological and environmental monitoring of occupational exposure of pharmaceutical plant workers to methotrexate. Int. Arch. Occup. Environ. Health 65(6): 401-403, 1994.

Date Last Revised: 04/20/2006

Monitoring Methods used by OSHA

Primary Laboratory Sampling/Analytical Method (SLC1):

  • sampling media: OSHA Versatile Sampler (OVS-2) 13 mm XAD-2 Tube (270/140 mg sections, 20/60 mesh) with Glass Fiber filter enclosed
    analytical solvent: 0.4 M sodium carbonate in (75:25) water:methanol
    maximum volume: 120 Liters
    maximum flow rate: 1.0 L/min
    current analytical method: High Performance Liquid Chromatography; HPLC/UV
    method reference: OSHA Analytical Method (OSHA PV2146)
    method classification: Partially Validated

Bulk Method:

  • Limit the amount of bulk submitted to one gram or one mL.

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