||Chemical Sampling Information
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 (RTECS) Identification Number: MA1225000
Chemical Description and Physical Properties: Bright yellow-orange, odorless, crystalline powder
molecular formula: C20H22N8O5
molecular weight: 454.4
melting point: 185-204°C (monohydrate)
International Agency for Research on Cancer (IARC) carcinogenic classification: Group 3, not classifiable as to its carcinogenicity to humans [1021 KB PDF]
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
- OSHA does not have a PEL for methotrexate.
- 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.
- Except for rare cases of allergic contact dermatitis, adverse health effects of occupational exposure to methotrexate have not been reported.
- 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.
- 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.
Date Last Revised: 04/20/2006
Monitoring Methods used by OSHA
- 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.
Laboratory Sampling/Analytical Method:
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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