Potential Health Hazards
RESPIRATORY EFFECTS
The predominant health effect of MDI and TDI is on the respiratory tract. Both chemicals have been shown to be portal-of-entry toxicants.
INHALATION OF VAPORS AND MISTS
MDI:
At room temperature, MDI has a relatively low vapor pressure in comparison to other organic chemicals. The vapor pressure of MDI largely explains the very low to nondetectable airborne concentrations found during most applications. Studies show that airborne concentrations of MDI are associated only with processes or applications that involve heating (well above 100 degrees F) and/or spraying (aerosolizing).
TDI:
The vapor pressure of TDI is higher than MDI and at a typical room temperature (i.e., 70°F) the concentration of vapor in the air can exceed the OSHA Permissible Exposure Limit (PEL) of 20 ppb. Thus protective measures, including the use of engineering controls (e.g., local exhaust ventilation), appropriate personal protective equipment (e.g., respiratory protection) or other workplace practices (e.g., proper handling and storage), etc., are taken whenever there is potential exposure to (unknown) airborne concentrations of TDI.
Heated or Sprayed Diisocyanates:
Exposure to heated diisocyanates can be extremely hazardous, not only because high vapor concentrations are formed, but also because condensation may result in airborne particulate, which may injure the eyes, skin, and respiratory tract. Similarly, spray mists can impose a significant health hazard.
Odor Threshold:
Reported odor threshold values for chemicals often are expressed in wide ranges because “odor” threshold testing has historically lacked a consistent approach. The reasons for the variation in reported odor thresholds include the chemical purity, the mode of presentation of the challenge agent to the individual, the influence of extraneous factors in how the odor is introduced, and the type of observer used (i.e., age, gender, race).
Two studies on the odor threshold for MDI and TDI, respectively, are summarized below:
- MDI: There is no reliable odor threshold for MDI reported. Nevertheless, the reported value of 0.4 ppm (400 ppb) suggests that if MDI is detected by smell, overexposure is likely to have occurred (Woolrich, 1982).
- TDI: In one study (Henschler et al., 1962), recognition of the odor of TDI was achieved by 90% of the panel of volunteers at 0.05 ppm (50 ppb) TDI. Thus, if TDI is detected by odor, most likely overexposure has occurred.
RESPIRATORY IRRITATION
The reactivity of the diisocyanates with the respiratory tract can cause irritation and inflammation at high concentrations. Irritating substances cause a decrease in respiratory rate in mice and rats. The RD50 (50% reduction in respiration rate) of MDI is 32 mg/m3 in mice (Weyel and Schaffer, 1985) and the RD50 of TDI is 1.4 mg/m3 (0.2ppm) in mice (Sangha and Alarie, 1979).
RESPIRATORY SENSITIZATION
Respiratory sensitization results in hyperreactivity of the airways following inhalation of an allergen. Sensitization includes two phases: the first phase is induction of specialized immunological memory in an individual by exposure to an allergen. The second phase is elicitation, i.e., production of a cell-mediated or antibody-mediated allergic response by exposure of a sensitized individual to an allergen. There are several substances in the workplace, including diisocyanates, which can cause respiratory sensitization. One of the outcomes of respiratory sensitization can be occupational asthma.
DIAGNOSIS
It is important to correctly diagnose occupational asthma attributed to diisocyanates. The basis for a diagnosis of “diisocyanate-induced asthma” includes confirming the diagnosis of asthma and then establishing that the reaction occurs in relation to exposure to diisocyanates and not to other irritants in the workplace.
A first step toward the diagnosis is taking a careful history regarding the following:
- history consistent with asthma;
- relief of symptoms during weekends or vacations, and recurrence upon returning to work; and
- tendency for the symptoms to be worse at the end of the workday.
Carefully controlled specific provocative inhalation tests with diisocyanates may be used, but are usually not readily available. Such bronchial provocation testing uses elaborate exposure equipment and experienced technicians. Confirming work-related bronchoconstriction by demonstrating decrement of lung function in association with workplace exposures is usually sufficient to confirm or contradict the presumptive diagnosis. Immune testing, including diisocyanate-specific IgE and IgG testing in blood serum, has not been standardized and validated and as a consequence has not shown adequate specificity and sensitivity for
diagnosis (Budnik, 2012).
ALVEOLITIS OR HYPERSENSITIVITY PNEUMONITIS
On occasion, alveolitis or hypersensitivity pneumonitis, may result from diisocyanate exposure. In contrast to bronchial asthma, alveolitis has been reported in isolated case reports usually when there have been gross overexposures. Symptoms may appear 6 to 8 hours after exposure and may include malaise, joint pain, fever, cough, and shortness of breath. Chest X-rays may show “shadows” on the lungs.
The condition usually subsides upon removal from exposure.
Diagnosis of the condition requires the following criteria: clinical (a flu-like syndrome) with fever and shortness of breath, radiographic (lung infiltrates), physiologic (restrictive pattern in lung function) and immunologic (presence of specific IgG antibodies) (Baur, 1995). Other investigators have not found the IgG antibodies in all cases and concluded that the clinical syndrome in the presence of non-irritating concentrations of diisocyanates as a sensitive indicator of the disease (Vandenplas, 1993). Signs and symptoms usually disappear in a few days upon removal from exposure. However, if exposure is continued, chronic lung fibrosis, impaired gas exchange, labored breathing, and reduced physical fitness may develop.
SKIN EFFECTS
DERMAL IRRITATION
Repeated contact with liquid diisocyanates may discolor the skin or cause signs of irritation such as redness, irritation, swelling, and/or blistering. If diisocyanates accidentally come in contact with the skin, wash immediately with soap and water. Cured material is difficult to remove; however, practical experience has demonstrated that some of the best ways to remove it is with corn oil, petroleum jelly or industrial skin cleansers (e.g., D-TAMTM Safe Solvent: Colorimetric Laboratories, Inc.).
ALLERGIC CONTACT DERMATITIS
Dermal exposure to diisocyanates may also result in allergic contact dermatitis (ACD). ACD is a rare occurrence with MDI and TDI. ACD is a two-step process: the first phase is induction of specialized immunological memory in an individual by exposure to an allergen; the second phase is elicitation -- the production of a cell-mediated allergic response by re-exposure of a sensitized individual to an allergen. Persons previously sensitized can experience allergic skin reaction with the symptoms of reddening, itching, swelling, and rash upon dermal contact.
Evidence in animal studies suggests that repeated dermal exposure may also play a role in the development of respiratory sensitization. Both TDI and MDI have induced respiratory hypersensitivity responses when applied to, or injected into, the skin of animals and followed by inhalation exposure. Based on these findings, it is strongly recommended that skin contact with diisocyanates be avoided.
CARCINOGENICITY
For hazard communication purposes under OSHA Standard 29 CFR, Part 1910.1200, TDI is listed as a potential carcinogen by the National Toxicology Program (NTP) and the International Agency for Research on Cancer (IARC). Both agencies based their evaluation of TDI as a potential carcinogen primarily on an oral study in which high doses of TDI were reported to cause cancer in animals. This study, in which rats and mice were administered high doses of TDI in corn oil by oral gavage, has been found to contain deficiencies that resulted in the formation of toluene diamine (TDA), a known animal carcinogen. TDI did not cause cancer or result in the formation of detectable levels of free TDA when laboratory animals were exposed by inhalation, by far the most likely route of exposure (Loser, 1983).
A study to determine the chronic toxicity and potential carcinogenicity of MDI has been conducted. Male and female rats were exposed 6 hours/day, 5 days/week for two years to an atmosphere of respirable polymeric MDI aerosols at concentrations of 0.2 mg/m3, 1.0 mg/m3, or 6.0 mg/m3 (Reuzel et al., 1994). A low incidence of primarily benign lung tumors in Type II cells were seen at only the highest concentration. In a second study (Hoymann et al., 1995), female rats were exposed 17 hours/day, 5 days/week for 2 years to an atmosphere of respirable monomeric MDI aerosols at concentrations of 0.23 mg/m3, 0.70 mg/m3 or 2.03 mg/m3. A benign lung tumor was only observed in a single rat at 2.03 mg/m3.
Several in vitro studies used solvents that cause rapid hydrolysis of TDI to its diamine, a known mutagen, and the results have been discounted (Herbold et al., 1998; Seel et al., 1999). A weight of evidence assessment of in vitro and in vitro testing indicates that TDI has no mutagenic activity. Numerous in vitro mutagenicity studies have been done on MDI that do not show a mutagenic potential, except under conditions using solvents which cause rapid hydrolysis of MDI to its diamine, a known mutagen (Herbold et al., 1998; Seel et al., 1999). This may account for the mutagenic findings. The majority of the studies using a different solvent have not resulted in mutagenicity.
The results of these studies suggest that the incidence and delayed occurrence of lung tumors is consistent with a nongenotoxic mode of action since MDI-DNA adducts are not detected in organs with tumors or at doses associated with cell proliferation. Since lung tumors only were observed at a concentration orders of magnitude higher than established occupational exposure guidelines, MDI is unlikely to pose a significant cancer risk to workers.
Several epidemiology studies were unable to show a significant link between employment in polyurethane manufacturing and cancer deaths:
- 40-year cohort study of TDI polyurethane foam manufacturing in England and Wales (Sorahan and Pope, 1993; Sorahan and Nichols, 2002)
- 37-year cohort study of TDI polyurethane foam manufacturing in US (Schnorr et al., 1996)
- 29-year cohort study of TDI and MDI polyurethane foam manufacturing in Sweden (Hagmar et al., 1993a; Hagmar et al., 1993b)
- 40-year cohort study of TDI and MDI. Follow-up of the Hagmar et al. studies in Sweden (Mikoczy et al., 2004)
No Comments