Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

MACROPHAGE INFLAMMATORY PROTEIN 2 (MIP-2)

NFPA

PRODUCT USE

alpha- Class chemokine. Chemokines of this subfamily primarily act as neutrophil
chemoattractants and activators, including neutrophil degradation with release of
myeloperoxidase and other enzymes. MIP- 2 was originally identified as a heparin- binding
protein secreted from murine macrophage cell lines in response to endotoxin stimulation.
The precursor form of MIP- 2 consists of 100 amino- acis. To generate mature MIP- 2, the
precursor cleaves its amino- terminal 27 amino- acids. MIP- 2 shows 60% amino- acid
homology to human GRObeta and human GROgamma. The material produces chemokinesis. The name
chemokine was proposed at the third International Symposium of Chemotactic Cytokines in
1992. Chemokine is a combination of chemoattractant and cytokine describing proteins that
are structurally defined as chemoattractants for leukocytes. Chemokines have observed
sequences indicating that they arose from a common ancestral gene. The chemokine
superfamily is divided into two branches based on whether the first two cysteine motifs
are adjacent (the C- C branch, beta- chemokine) or separated by an amino- acid (the C- X-
C branch, alpha- chemokine). The alpha- chemokines are potent chemoattractants for
neutrophils and may also act as activators which initiate neutrophil degradation with the
release of myeloperoxidase and other enzymes. The beta- chemokines act primarily as
chemoattractants and activate monocytes, dendritic cells, T- lymphocytes, natural killer
cells, B lymphocytes, basophils and eosinophils. In addition to these properties,
chemokines have lymphocyte adhesion- inducing properties. Chemokines are probably required
for the migration into interstitial spaces. Several chemokines produce pyrogenic effects
which can be inhibited by cyclooxygenase blockers; others cannot. Chemokines attract
myeloid cell types in vitro, while the production and/or secretion of most chemokines, in
vivo, is induced by lipopolysaccharide, tumour necrosis factor or interleukin 1. Chemokine
secretion by tumours inhibits tumour growth. The growth of sarcoma clones secreting MCP- 1
(an alpha- chemokine) is inhibited as the amount of MCP- 1 increases. Most mature
chemokines consist of 70 amino- acids and have internal disulfide bonds. The C- X- C
branch or alpha- branch of the chemokines is derived from the proteolytic processing of a
single protein. All known alpha- chemokines are 25- 90% identical to each other and are
encoded by genes that cluster on human chromosome 4q12- q21. The C- X- C chemokine genes,
with the exception of PF4, have a four exon and a three intron structure. The C- C branch
or beta- branch of the chemokines was identified by molecular cloning. All known beta-
chemokines are 25- 70% identical to each other and are encoded by genes that cluster on
human chromosome 17. The C- C chemokine genes have a three exon and two intron structure.
The alpha (C- X- C) chemokine family includes CINC- 1, KC, MIP- 2, PBSF/SDF1, IL- 8,
GROalpha, GRObeta, GROgamma, ENA- 78, NAP- 2, GCP- 2, IP- 10, PF- 4, NAP- 4, MIG, betaTG,
CTAP and PBP. The beta (C- C) chemokine family includes C10, Eotaxin, HCC- 1, JE, MIP-
1alpha, MIP- 1beta, RANTES, MCP- 1, MCP- 2, MCP- 3, MCP- 4 and l- 309.

SYNONYMS

"MIP-2/ MIP2", protein/polypeptide, chemokine, "chemotactic cytokine", alpha-chemokine

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Although ingestion is not thought to produce harmful effects, the material may still be damaging to the health of the individual following ingestion, especially where pre-  existing organ (e.g. liver, kidney) damage is evident. Present definitions of harmful or toxic substances are generally based on doses producing mortality (death) rather than those producing morbidity (disease, ill-health). Gastrointestinal tract discomfort may produce nausea and vomiting. In an occupational setting however, ingestion of insignificant quantities is not thought to be cause for concern.  

EYE

  Although the material is not thought to be an irritant, direct contact with the eye may produce transient discomfort characterized by tearing or conjunctival redness (as with windburn).  The dust may produce eye discomfort causing smarting, pain and redness.  

SKIN

  The material is not thought to produce adverse health effects or skin irritation following contact (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  

INHALED

  The material is not thought to produce adverse health effects or irritation of the respiratory tract (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable control measures be used in an occupational setting.  Respiratory sensitization may result in allergic/asthma like responses; from coughing and minor breathing difficulties to bronchitis with wheezing, gasping.  

CHRONIC HEALTH EFFECTS

  There is some evidence that inhaling this product is more likely to cause a sensitization reaction in some persons compared to the general population.  

  Principal routes of exposure are usually by inhalation of generated dust and skin contact.  Exposure to small quantities may induce hypersensitivity reactions characterized by acute bronchospasm, hives (urticaria), deep dermal wheals (angioneurotic edema), running nose (rhinitis) and blurred vision . Anaphylactic shock and skin rash (non-thrombocytopenic purpura) may occur. An individual may be predisposed to such anti-body mediated reaction if other chemical agents have caused prior sensitization (cross-sensitivity).  Dusts produced by proteins can sometimes sensitize workers like other foreign bodies. Symptoms include asthma appearing soon after exposure, with wheezing, narrowing of the airways and breathing difficulties. There may also be a chronic cough, phlegm, fever, muscle pains, fatigue and airway obstruction; chest X-rays may show a characteristic net-  like pattern or scarring at the tip and base. There may also be chest discomfort, headache, stomachache and a general feeling of unwellness. Often the clinical picture is similar to "farmer's lung" and other allergic lung inflammations. Prolonged contact with the skin can cause pain, redness, inflammation and ulceration. Repeated attacks can cause loss of lung function due to scarring.