COOPERATIVE EXTENSION UNIVERSITY OF CALIFORNIA ENVIRONMENTAL TOXICOLOGY NEWSLETTER

COOPERATIVE EXTENSION UNIVERSITY OF CALIFORNIA
ENVIRONMENTAL TOXICOLOGY NEWSLETTER

Chlorine Gas Toxicity from Mixture of Bleach with Other Cleaning Products -- California

From October 1987 through November 1989, five episodes of chlorine gas exposure with toxicity to at least 14 persons occurred at two state hospitals in California. Each hospital provides inpatient treatment to approximately 1000 forensic psychiatric patients. As part of their rehabilitation programs, selected patients perform cleaning duties under the supervision of janitors or nursing staff. Each incident occurred during the performance of these duties and involved the mixture of bleach (sodium hypochlorite) and a phosphoric acid cleaner by inpatients. This mixture produced chlorine gas and other chemical byproducts and resulted in temporary illness in exposed persons.

Episode 2. On December 19, 1987, a patient mopped a bathroom floor with a 4% phosphoric acid solution, then rinsed the floor with water. Immediately after he applied a bleach and water solution to the floor, a noxious gas with a strong odor was emitted. The mixture was poured down a drain, and the floor was again rinsed with water; however, because the room's exhaust fan was inoperative and windows had been sealed shut, the gas dispersed throughout the ward and caused symptoms in other patients. The ward was evacuated; patients and staff returned after 1 1/2 hours when the odor had dissipated. Within an hour of their return, additional patients and staff complained of symptoms including nausea, eye irritation, tearing, sore throat, headache, cough, and chest tightness; one patient had an acute exacerbation of asthma. The ward was reevacuated until the following day. The local fire department assisted with ventilation.

Beginning December 29, controls were instituted on the storage and use of the phosphoric acid cleaner at hospital A. The cleaner was dispensed by housekeeping supervisors to janitors, who kept it locked in storage areas accessible to employees only.

On December 7, 1988, a patient assisting in janitorial duties mixed bleach with phosphoric acid cleaner. Immediately a noxious gas with a strong odor was detected and prompted the evacuation of two wards for 1 1/2 hours. Fire department personnel using self-contained breathing equipment disposed of the chemicals and ventilated the area.

The patient experienced vomiting, cough, and inspiratory discomfort; elevated blood pressure and fever were noted when the patient was treated in the emergency room. Five employees who helped evacuate the ward complained of symptoms including eye irritation and shortness of breath. Employees and patients returned approximately 1 1/2 hours after the area was ventilated. After this incident, hospital B instituted warning labels on all chemical cleaning products and posted precautionary (i.e., do not mix) signs on janitorial closets. Bleach and acidic cleaning products were restricted to use by staff. No further incidents involving phosphoric acid products have occurred at this hospital.

The label of the phosphoric acid cleaner involved in all five incidents did not list the active ingredient nor warn of the potential for toxic reactions when phosphoric acid was mixed with other chemicals. The material safety data sheet (MSDS) did not describe potentially toxic chemical reactions or incompatibilities. The labels and MSDSs of two other products containing phosphoric acid in use at hospital A, including one with a 30% acid concentration, also lacked information on reactions and incompatibilities with hypochlorite.

Editorial Note: The chemicals involved in the first three incidents were a standard household bleach (5.25% sodium hypochlorite solution [NaOCl]) and a 4% phosphoric acid (H3PO4) cleaning agent. When sodium hypochlorite and an acid are mixed, chlorine gas and water are released. Chlorine gas reacts with the water to form hydrochloric and hypochlorous acids. Chlorine gas may cause a variety of symptoms as a function of the severity of exposure. Hydrochloric acid also causes inflammation that may, along with nascent oxygen release, be one of the mechanisms of tissue damage by chlorine.

Mild mucous membrane irritation may occur in some persons after several hours at levels as low as the threshold limit value (TLV) of 1 ppm; this TLV may warrant reassessment. A level of at least 3 ppm may cause extreme irritation of the eyes and respiratory tract, but a detectable odor is usually not present below 3.5 ppm. Symptoms following exposure to chlorine have included irritation of the eyes, nose, and throat; dizziness; cough; and chest pain or constriction. Severe exposure may cause pulmonary edema, bronchiolar and alveolar damage, and pneumomediastinum.

When bleach is mixed with ammonia-containing compounds, monochloramine (NH2Cl) and dichloramine (NHCl2) are formed, which may produce tearing, respiratory tract irritation, and nausea. These compounds decompose in water to hypochlorous acid and free ammonia gas; the former combines with moisture forming hydrochloric acid and toxic nascent oxygen; the latter is a respiratory and mucous membrane irritant and can cause pulmonary edema and pneumonia.

Three approaches can be implemented to prevent potential toxic exposures in institutional and other industrial settings from mixtures of bleach with other cleaning agents:

In New Jersey, cancers among children aged 0-14 years account for fewer than 1% of all cancers diagnosed annually; however, childhood cancers account for the greatest number of years of potential life lost from cancer. This report summarizes a study by the New Jersey State Department of Health (NJSDH) that determined the incidence and death rates for the most frequent cancers among children aged 0-14 years in New Jersey during 1979-1985; these rates are compared with those for the United States for a comparable period. Incidence data were obtained from the New Jersey State Cancer Registry.

From 1979 through 1985, incidence rates of childhood cancers remained relatively stable in New Jersey, while death rates decreased steadily. Although incidence rates for total childhood cancer in New Jersey were higher than the national rates, death rates for New Jersey were virtually identical to U.S. rates.

During the 7-year period, cancer was diagnosed annually in an average of 240 children in New Jersey, most (83%) of whom were white. Each year, an average of 64 children died from cancers -- leukemia (31% of deaths), brain and central nervous system cancers (20%), lymphomas (11%), renal cancer (6%), bone and joint cancer (4%), eye and orbit cancer (3%), and all other cancers (24%).

Editorial Note: Although the overall incidence of cancer is low among children, cancer is the major cause of deaths attributed to disease in children in the United States. During 1950-1985, the incidence rate of childhood cancers increased by 32%, while the death rate decreased 56% - primarily because of advances in treatment of many forms of childhood cancers. In 1991, an estimated 7800 new cases of childhood cancers will occur in the United States, and approximately 1500 children will die from cancers.

New Jersey accounts for approximately 3.7% of the estimated 7800 childhood cancers that occur annually in the United States. Although the incidence rate of childhood cancers in New Jersey was higher than that of the United States, similarities in death rates suggest that health-care providers and programs in New Jersey have been successful in aggressively screening, identifying, and treating childhood cancers.

Parents can assist in early detection of childhood cancers by ensuring that children are evaluated for problems such as unexplained fatigue or fever, frequent headaches, unusual masses or swelling, increased bruising, and unexplained weight loss.

In 1964, the first Surgeon General's report on smoking focused on the health hazards associated with cigarette smoking. From 1965 through 1987, the overall prevalence of cigarette smoking among adults in the United States declined by approximately 0.5 percentage points per year. To determine the prevalence of smoking among adults in the United States in 1988, the Occupational Health Supplement (OHS) of CDC's National Health Interview Survey collected information on cigarette smoking from a representative sample of the U.S. civilian, noninstitutionalized population aged > 18 years.

For 1988, the OHS included the following questions on smoking behavior: "Have you smoked at least 100 cigarettes in your entire life?" and "Do you smoke cigarettes now?" Among persons who reported smoking at least 100 cigarettes, current smokers were defined as those who reported being a smoker at the time of the interview, and former smokers, as those who were not current smokers. Both current and former smokers were classified as ever smokers. The proportion of persons who had stopped smoking was defined as the number of former smokers divided by the number of ever smokers. Current smokers were asked, "On the average, about how many cigarettes a day do you smoke?" Data were available on cigarette smoking status for approximately 44,000 persons aged >18 years and were weighted to provide national estimates. Ninety-five percent confidence intervals (CIs) were calculated using SESUDAAN (a standard errors program for computing of standardized rates from sample survey data).

Based on the survey, in 1988 an estimated 91.1 million (51.9%) adults in the United States were ever smokers, and 49.4 million (28.1%) were current smokers. Current smokers included 30.8% of all men (25.6 million) and 25.7% of all women (23.7 million). In all age groups except 18-24-year-olds, the prevalence of smoking was higher among men than women; smoking was most prevalent among persons 25-64 years of age. The overall prevalence of smoking was higher among blacks (31.7%) than whites (27.8%), and lowest among persons of other races (23.8%). The overall prevalence also was higher among non-Hispanics (28.4%) than Hispanics (23.5%). The prevalence of smoking was highest among persons with less than a high school education (34.0%) and with only a high school education (32.0%).

The prevalence of smoking was significantly higher among separated and divorced persons (42.6%) than among persons in other marital categories: married (27.4%), never married (26.5%), and widowed (19.5%).

In 1988, 41.8 million (45.8%) ever smokers were former smokers. The proportion of men (49.0%) who had stopped smoking was higher than that of women (42.0%), and the proportion of whites (47.6%) who had stopped smoking was higher than that of blacks (32.4%). The proportion of Hispanics who had stopped smoking (44.9%) was similar to that for non-Hispanics (45.9%). The proportions of adults with less than a high school education who had stopped smoking (41.1%) and of adult high school graduates who had stopped smoking (41.3%) were lower than those for persons with some college education (47.7%) and for college graduates (63.1%).

Overall, the mean number of cigarettes smoked per day by current smokers in 1988 was 21.3. In general, the mean number of cigarettes smoked by men was higher than the number smoked by women. Whites smoked more cigarettes per day than did blacks and persons of other races, and non-Hispanics smoked more cigarettes per day than did Hispanics. In 1988, 27.0% of smokers smoked 25 or more cigarettes per day.

Editorial Note: The findings in this report indicate that, from 1987 to 1988, the overall prevalence of smoking among adults >18 years of age declined from 28.8% to 28.1% - approximately 0.7 percentage points. In addition, in 1988, the proportion of ever smokers who were former smokers was 45.8%, compared with 44.2% in 1987.

The higher rates of cigarette smoking among separated and divorced persons appear to reflect higher rates of smoking initiation before the usual age of marriage. In addition, separated and divorced persons were less likely to have quit smoking than married persons. Social support provided in marriage may increase the probability of cessation, while stress (which has been associated with difficulty in quitting) from marital discord may decrease the likelihood of quitting.

Cigarette smoking is the single most important preventable cause of death in the United States. One of the national health objectives for the year 2000 (objective 3.4) is to reduce the prevalence of cigarette smoking among adults to no more than 15%. To achieve this goal, the current rate of decline must be doubled.

Health-care providers and public health agencies must increase efforts to prevent the initiation of smoking and, for smokers, to support attempts to quit and maintain cessation. Persons with less than a high school education and in low socioeconomic groups are at especially high risk for becoming smokers. In addition to directing interventions toward these groups, smoking control and prevention efforts will require intensified public health education, increased emphasis on school health education, and enactment and enforcement of effective health-promoting policies and laws.

In 1988, an estimated 434,000 persons in the United States died as a result of cigarette smoking. About three fourths of adults who have ever been regular cigarette smokers reported trying their first cigarette before their 18th birthday, and about half of them had become regular smokers by that time.

Overall, 15.7% of respondents reported smoking on 1 or more days during the month, and 11.5% reported smoking on 1 or more days during the week before the survey. Patterns were similar by gender in all categories, except among persons 18 years of age. The prevalence of smoking was higher among white youth than among black youth. Although the prevalence of smoking in the past month was lower among Hispanic (11.7%) than among non-Hispanic (16.1%) youth, the prevalence of smoking in the past week was similar in each group (9.3% and 11.8%, respectively). Prevalence of smoking in the past month and in the past week increased directly by age.

Among youth 17-18 years of age, the prevalence of smoking during the previous week was substantially higher among dropouts (43.3%) than among school attenders/HS graduates (17.1%). Among school attenders/HS graduates, the prevalence of smoking during the previous week was similar by gender (males: 17.5%; females: 16.7%). However, dropouts who were male (51.7%) were more likely to report having smoked during the previous week than were dropouts who were female (33.3%). Among school attenders/HS graduates, 19.3% of whites and 5.7% of blacks reported smoking during the previous week. Similarly, dropouts who were white (46.1%) were more likely to report having smoked during the previous week than were dropouts who were black (17.1%).

Editorial Note: The findings in this report are consistent with findings from three other recent national surveys that measure smoking by youth: rates of smoking are similar for males and females and higher for whites than blacks. In addition, the findings from TAPS (Teenage Attitudes and Practices Survey) confirm previous reports of higher smoking rates among dropouts and suggest gender and racial differences in smoking prevalence among dropouts. Differences in overall prevalence estimates between surveys may be explained by the mode of data collection (i.e., household interview vs. school-based, self-administered questionnaire), composition of the samples, varying response rates, and the wording of questions.

Cigarette use among U.S. youth appears to have declined sharply in the late 1970s and stabilized in the 1980s, especially among white youth. The findings from TAPS underscore the need for interventions that focus on both in-school and out-of-school youth. The national health objectives for the year 2000 have established four relevant targets for this problem:

establish tobacco-free environments in all elementary, middle, and secondary schools and include tobacco use prevention programs in school curricula (objective 3.10); enact and enforce state laws nationwide prohibiting the sale and distribution of tobacco products to youth aged <19 years (objective 3.13);implement state plans nationwide to reduce tobacco use, especially among youth (objective 3.14); and eliminate or severely restrict all forms of tobacco product advertising and promotion to which youth < 18 years of age are likely to be exposed (objective 3.15).

Marylynn V. Yates, Ph.D.
Ground Water Quality Specialist
Department of Soil and Environmental Sciences
University of California, Riverside

In 1985, the Pesticide Contamination Prevention Act (AB2021) was passed specifically to try to prevent or minimize future ground water contamination by pesticides. This act states that the use of a pesticide will be restricted if it is detected in the ground water or found in the soil at or below the deepest of the following three depths: 8 feet below the soil surface, below the root zone of the crop, or below the soil microbial zone. Only pesticides that the California Department of Food and Agriculture (CDFA) is satisfied are in ground water as a result of normal, legal agricultural use are subject to AB2021. An important fact to note about AB2021 is that it applies to all pesticides, regardless of whether or not they have any effects on health. In addition, the act does not prescribe a minimum concentration where action must be taken. This means that any pesticide found in ground water or in the soil at the depth described above at any concentration will be subject to restricted use under AB2021. The severity of the use restrictions imposed by CDFA will, however, take into consideration health effects, site conditions, and the availability of alternative materials.

The act provides for the establishment of Pesticide Management Zones (PMZs). PMZs are 1 square mile areas around a well where a pesticide has been detected, and thus the ground water is considered to be vulnerable to contamination. To date, five pesticides have been placed on the list of "detected leachers" and some or all of their uses have been restricted in their respective PMZs (see Table 1).

Pesticide	Restriction
Atrazine	all outdoor agricultural, outdoor industrial and outdoor institutional uses prohibited in atrazine PMZs
Diuron,(Karmex); Bromacil,(Hyvar); Simazine,(Princep)	all non-crop uses prohibited in the respective PMZs
Prometon,(Pramitol)	all agricultural, outdoor industrial and outdoor industrial uses prohibited in prometon PMZs
Aldicarb	fall applications will be prohibited and rates allowed per acre reduced by 50%

In addition to the pesticides that have been detected in ground water, AB2021 requires that CDFA establish a list of suspected leachers. These are pesticides that, by virtue of their chemical and/or physical properties, may contaminate ground water even when used according to label directions. To identify suspected leachers, CDFA has established Specific Numerical Values (see Table 2). In order for a pesticide to be placed on the list, it must meet criteria for both mobility and persistence. In other words, it must meet EITHER the water solubility OR the soil adsorption coefficient AND the hydrolysis half-life OR aerobic soil metabolism half-life criteria.

Property	Value
Water solubility	> 3 ppm
Soil adsorption coefficient	< 1900 cm3 g-1
Hydrolysis half-life	> 14 days
Aerobic soil metabolism half-life	> 730 days

In August 1991, CDFA expanded the list of suspected leachers from 11 to 49 pesticides based on the above criteria. These pesticides, listed in Table 3, are used on a wide variety of field and food crops, as well as turf and ornamentals.

Pesticides on this list have not been found in ground water in the state of California, and no restrictions have been placed on their use at this time. However, ground water will be monitored for the presence of these pesticides. If any of the pesticides are found, they will become detected leachers, PMZs will be formed, and some restrictions will be placed on the use of the compound.

Table 3. Suspected Leachers as Defined by California Department of Food and Agriculture, August 1991

Excretion of plant toxicants into milk by lactating animals is minor when compared to other routes of elimination, but it can beimportant when the health of humans is considered. Many plant toxins have been detected in the milk of animals grazing on toxic plants. The human health risk is generally small, though, because there is a diluting effect of any possible toxicants through the bulk handling of milk, and most current management practices do not allow animals to graze on poisonous plants. The main threat is to those individuals who raise animals in areas infested with poisonous plants and for whom the animals are their sole source for milk.

Milk is an emulsion of lipids in an aqueous solution of proteins. Virtually any plant toxin or compound that is circulating in the body can enter milk. Most toxicants cross the mammary cell membranes by simple diffusion, thus chemicals bound to plasma proteins, associated with circulating lipids, or free in the plasma can easily cross through the mammary cells. Basic compounds, such as alkaloids, can become concentrated in milk because milk, with a pH of 6.5, is more acidic than plasma. Lipophilic compounds can also concentrate in milk.

Symptoms in infants and young animals due to concentrated toxins can be more severe than in the lactating animal itself. Additionally, infants and very young animals may not be able to metabolize or eliminate these compounds as efficiently as adults. Dangerous levels of plant toxicants can be transferred through the milk even before symptoms become evident in the mother.

The classic example of a plant toxicant excreted via milk is tremetol (or tremetone) in white snakeroot (Eupatorium rugosom) and rayless goldenrod (Haplopappus heterophyllus). Other plant toxicants excreted in the milk include pyrrolizidine alkaloids in Senecio, Crotalaria, Heliotropium, Echium, Amsinckia, Symphytum (comfrey), Cynoglossum (Hounds Tongue), and Festuca (tall fescue); piperidine alkaloids in Conium and tobacco; quinolizidine alkaloids in Lupinus; and glucosinolates in Amoracia (horseradish), Brassica (cabbage, broccoli, etc.), Limnanthes (meadowfoam), Nasturtium (watercress), Raphanus (radish) and Thlaspi (stinkweed).

The potential heath risk of these plant toxicants to humans is small. Current bulk handling of milk and intense management of dairy herds minimizes the possibility of being exposed to these compounds.

When evaluating the potential human health risk, these factors should be considered: (1) susceptibility of infants and very young children, (2) consumption of milk produced by lactating mothers who use potentially toxic herbal remedies, (3) availability of toxic plants to dairy animals, (4) long-term health effects from low levels of plant toxicants, and (5) consumption of milk from individual animals grazing on toxic plants.

In the August 23, 1991 Federal Register, FDA announced Commissioner David A. Kessler's decision to withdraw approval of two nitrofuran animal drugs used in food-producing animals, furazolidone and nitrofurazone. These drugs had been labeled and approved for antiprotozoal and other uses for a wide variety of conditions in poultry and swine. The Commissioner concluded as follows:

New evidence shows that there is a reasonable basis from which serious scientific questions may be inferred about the safety of furazolidone and nitrofurazone and the residues that result from their use.

Neither nitrofurazone nor furazolidone nor their metabolites have been shown to be safe under the conditions of use upon which the New Animal Drug Applications (NADAs) were approved.

No reliable detection method has been demonstrated to be able to detect nitrofurazone-related residues in edible tissues.

The Winterlin method of detection is incapable of measuring the metabolites of furazolidone. No other method of detection has been demonstrated to be able to measure these metabolites. Hence, no reliable method of detection has been demonstrated which is fully adequate to detect furazolidone-related residues in edible tissues.

A practical analytical method for the parent drug, furazolidone, and its metabolites does not exist. Therefore, it is impossible to quantify and qualify the nature of the residues of furazolidone.

A determination of the concentration of drug residues consisting of the parent drug, furazolidone, and its metabolites that is of no carcinogenic concern has not been adequately established.

Under the conditions of use, the actual concentration of drug residues of furazolidone has not been shown to be at or below the level of no carcinogenic concern.

The Commissioner withdrew approval for the drugs and revoked the regulations codifying the approval of these applications in the Code of Federal Regulations, Title 21, Parts 510.515, 558.4, 558.15, 558.262, and 558.370.

Several ophthalmic, intra-aural, intrauterine, and topical products will remain approved for use in nonfood-producing animals. CVM plans to add nitrofurans to the list of drugs not allowed for use under the extra-label drug use policy. Any extra-label use of these drugs in food-producing animals will come under the highest priority for regulatory attention, along with others already listed in Compliance Policy Guide 7125.06 on extra-label use of veterinary drugs in food-producing animals.

FDA has revoked its interim policy permitting the use of gentian violet at levels up to 8 parts per million (ppm) as a mold inhibitor in poultry feed (Federal Register, August 15, 1991). Marketing of gentian violet for use in any food animal species will be permitted only under provision of a food additive regulation or an approved new animal drug application (NADA). Currently, there are no published food additive regulations nor approved NADAs for gentian violet in food animals.

Studies conducted at the National Center for Toxicological Research demonstrated that gentian violet causes cancer in test animals and that residues of the substance occur in the edible tissues of chickens under the use permitted by the interim policy.

Gentian violet is not "grandfathered" under provision of the Drug Amendments of 1962.

Alternatives to the use of gentian violet have been available and in use for a number of years. FDA expects most poultry producers who currently use gentian violet as a mold inhibitor to switch to an alternative, e.g., propionic acid and its salts.

On December 4, 1990, California Assembly Bill 110 was introduced to the California Legislature and proposed to ban the Draize Eye and Skin Irritancy tests by manufacturers of cosmetics and household products. After several amendments and delays, AB 110 passed both California Houses and went to Governor Pete Wilson's office for signing on August 28, 1991. Governor Wilson vetoed the bill on September 10, 1991, stating that sufficient alternative tests are unavailable at this time. Not only have similar bills been submitted to the California Legislature in recent years, but numerous other states have joined this trend.

In 1989, there were 36 bills introduced into the legislatures of 23 states. Eight of these bills concerned the protection of animals and addressed specifically their use in testing products such as cosmetics and household laundry detergents for eye and skin irritancy. In the first seven months of 1991, there were 42 animal testing-related bills introduced into the legislatures of nineteen states. Seventeen of these 42 bills would make it illegal to use Draize skin and eye irritancy tests on live animals.

Since this issue surfaced, was introduced into several legislatures and reintroduced in many, the Food and Drug Administration (FDA) has echoed a strong, consistent message; viz., Enactment of such a bill would pose serious problems from a public health perspective. In a letter to California's Governor Pete Wilson dated September 3, 1991, FDA's Commissioner, Dr. David Kessler, expanded on this public health message as follows:

"The Food and Drug Administration (FDA) has encouraged the development of alternative test methods and is aware that many such tests are in various stages of evolution. However, none of these tests has been accepted by the scientific community as replacements to the Draize tests. For the foreseeable future, there appears to be little chance of totally replacing animal testing, and we will need to continue to rely on these methods to ensure safety. FDA's basic positions on the use of non-animal alternatives are as follows:

Moreover, California legislators and Governor Wilson have heard similar messages from other federal agencies including the Environmental Protection Agency (EPA), Consumer Product Safety Commission (CPSC), and the National Institutes of Health (NIH). Additionally, former Surgeon General Dr. C. Everett Koop, in a press conference held April 29, 1991, expressed his concern on the risks of legislation banning animal use when, to date, alternatives have not been found to replace animals in testing for eye irritancy.

Underlying this controversy is a popular but erroneous belief that there are alternatives available but scientists and government regulators choose not to recognize them. This notion is supported by a common sense philosophy that deduces the following conclusion: If we can put a man on the moon, replace organs in people, develop a sophisticated war-machine as demonstrated in the Persian Gulf, then we must be able to replace animals with computer technology and in vitro techniques such as tissue cultures and bioassays.

Research and development of non-whole-animal testing methodologies is a very complex, new arena that spans several scientific disciplines and is rapidly growing. Indeed, there are several promising screens under development, and in some cases in use, that reduce the number of animals needed for testing a proposed product and/or reduces the discomfort for those animals that are used. However, the human eye is an extremely complex organ; its intricate interactions with other body systems make it extremely difficult to develop a surrogate that responds similarly to potential ocular irritants. The undeniable fact remains; at this time, no method has been developed that replaces the whole animal model in eye irritancy testing.