PENICILLAMINE

Penicillamine is a heavy metal chelator of copper, lead, and mercury. It promotes the excretion of these metals in the urine and has been used to treat cystinuria, Wilson's disease, and heavy metal poisoning. The drug has also been very successful for rheumatoid arthritis patients (Prod Info DEPEN(R) titratable oral tablets, 2009; Prod Info CUPRIMINE(R) oral capsules, 2007).
In rodent models of thallium intoxication, D-penicillamine combined with Prussian blue decreased mortality and tissue levels of thallium without causing redistribution to brain (Rios & Monroy-Noyola, 1992; Barroso-Moguel et al, 1994). D-penicillamine alone caused redistribution of thallium to brain and increased mortality (Rios & Monroy-Noyola, 1992; Barroso-Moguel et al, 1994).

FORMS

Penicillamine is available as 125 mg and 250 mg capsules, and as 250 mg tablets (Prod Info DEPEN(R) titratable oral tablets, 2009; Prod Info CUPRIMINE(R) oral capsules, 2007).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Penicillamine is a heavy metal chelator of copper, lead, and mercury. It promotes the excretion of these metals in the urine and has been used to treat cystinuria, Wilson's disease, and heavy metal poisoning. Penicillamine has also been used to treat patients with severe, active rheumatoid arthritis.

PHARMACOLOGY: Penicillamine is a degradation product of penicillin and acts as a chelator of heavy metals. It chelates copper, lead, and mercury. Although in vitro studies indicate copper binding at 1 gram penicillamine to 200 mg copper, only about 2 mg of copper are excreted by 1 gram of penicillamine for a 2% efficiency. Penicillamine is also used to treat cystinuria by forming a soluble urinary complex thus reducing the formation risk of renal stones. It also chelates iron and probably other heavy metals to form stable, soluble complexes that are readily excreted in the urine. The mechanism of action of penicillamine in rheumatoid arthritis is not known, but may involve improvement of lymphocyte function. It markedly reduces IgM rheumatoid factor and immune complexes in serum and synovial fluid, but does not significantly lower absolute concentrations of serum immunoglobulins.

TOXICOLOGY: The L isomer and racemic mixture are more toxic than the D isomer. The N-acetylated form of DL-penicillamine has shown less toxicity than the DL mixture itself, and more similar to that of penicillamine.

EPIDEMIOLOGY: Overdose is rare.

WITH POISONING/EXPOSURE

Overdose data are limited. In general, overdose effects are anticipated to be an extension of adverse effects at therapeutic doses. Occupational asthma has been reported in a pharmaceutical company worker after chronic exposure to penicillamine.

WITH THERAPEUTIC USE

The following adverse effects have been reported following the therapeutic use of penicillamine: anorexia, nausea, vomiting, loss of taste, abdominal pain, optic neuritis, retinopathy, photophobia, lacrimation, conjunctival inflammation, proteinuria, nephrotic syndrome, glomerulonephritis, disturbance in copper and zinc metabolism, hypersensitivity reactions, thrombocytopenia, thrombotic thrombocytopenic purpura, leukopenia, polycythemia, aplastic anemia, lymphopenia, agranulocytosis, rashes, alveolitis, pulmonary hemorrhage, bronchial asthma, pleurisy, hemoptysis, bronchiolitis obliterans, and bilateral infiltrate, seizures, neuropathies, dystonia and various autoimmune responses (eg, polymyositis, myasthenia gravis, SLE, Goodpasture's syndrome, thyroiditis). In some studies, adverse effects occurred in as high as 62% of patients, with 36% experiencing symptoms which necessitated discontinuation of therapy. Most of these toxic side effects occur with chronic administration. The relationship to dose is unclear, as even patients taking small doses may develop toxicity. Although penicillamine has a structure very similar to penicillin, there does not appear to be extensive crossreactivity even though skin testing may show crossreactivity.

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

Prehospital gastrointestinal decontamination is generally not recommended because of the potential for persistent seizures and subsequent aspiration.

-RANGE OF TOXICITY

MAXIMUM TOLERATED EXPOSURE

No specific acute toxic dose has been established.

Carcinogenicity Ratings for CAS52-67-5 :

ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
EPA (U.S. Environmental Protection Agency, 2011): Not Listed
IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
MAK (DFG, 2002): Not Listed
NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

TOXICITY AND RISK ASSESSMENT VALUES

EPA IRIS

EPA Risk Assessment Values for CAS52-67-5 (U.S. Environmental Protection Agency, 2011):

Not Listed

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS52-67-5 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS52-67-5 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS52-67-5 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS52-67-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS52-67-5 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS52-67-5 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS52-67-5 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS52-67-5 (U.S. Environmental Protection Agency, 2010b):

Not Listed
Editor's Note: The D, F, and K series waste numbers and Appendix VIII to Part 261 -- Hazardous Constituents were not included. Please refer to 40 CFR Part 261.

EPA SARA Title III, Extremely Hazardous Substance List for CAS52-67-5 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS52-67-5 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS52-67-5 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS52-67-5 (EPA, 2005):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS52-67-5 (NFPA, 2002):

Not Listed

-PERSONAL PROTECTION

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

PROTECTIVE CLOTHING

CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 52-67-5.

Specific recommendations and test data for this chemical were not found in the available manufacturers' product literature. A complete list of consulted manufacturers and references is presented below.

-PHYSICAL HAZARDS

FIRE HAZARD

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS52-67-5 (NFPA, 2002):

Not Listed

FIRE CONTROL/EXTINGUISHING AGENTS

Editor's Note: An ERG guide with information appropriate to this material does not exist.

NFPA Extinguishing Methods for CAS52-67-5 (NFPA, 2002):

Not Listed

REACTIVITY HAZARD

Is relatively stable at a pH of 2 to 4.

EVACUATION PROCEDURES

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

AIHA ERPG Values for CAS52-67-5 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS52-67-5 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS52-67-5 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; United States Environmental Protection Agency Office of Pollution Prevention and Toxics, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 62 FR 58840, 1997; 65 FR 14186, 2000; 65 FR 39264, 2000; 65 FR 77866, 2000; 66 FR 21940, 2001; 67 FR 7164, 2002; 68 FR 42710, 2003; 69 FR 54144, 2004):

Not Listed

NIOSH IDLH Values for CAS52-67-5 (National Institute for Occupational Safety and Health, 2007):

Not Listed

CONTAINMENT/WASTE TREATMENT OPTIONS

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

SMALL LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

LARGE LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

149.2 (S Sweetman , 2001)

DESCRIPTION/PHYSICAL STATE

D-penicillamine has a slightly bitter taste and a characteristic odor (S Sweetman , 2001).

A fine, white crystalline powder (S Sweetman , 2001).

4.5-5.5 (1% solution) (S Sweetman , 2001)

SOLUBILITY

IN WATER

1 part in 9 (S Sweetman , 2001). The D form (hydrochloride) is freely soluble in water (Budavari, 1996).

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GENERAL BIBLIOGRAPHY

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40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.

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65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.

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PENICILLAMINE

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Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents