Vol. 3 No. 4 June 8, 1983



I. TMRC and Its Relation to ADI
II. Carbon Monoxide Intoxication
III. Cashew Nut Dermatitis
IV. Irrigation Pipe Associated Electrocution
V. Congenital Malformations
VI. Childhood Lead Poisoning
VII. Cytogenetic Patterns in Persons Living near Love Canal


This newsletter contains a variety of interesting topics which relate to the recent prominence that toxicology has achieved in many facets of life. I heard the presentation on the TMRC at the National IR-4 meeting in Washington D.C. earlier this year and I thought it was the clearest explanation of the concept that I have ever heard. I think that it could be of use to many farm and home advisors. The information about carbon monoxide is of special concern when you consider the rapid proliferation of unvented space heaters. The article on dermatitis induced by cashew nuts is included as an addendum to the recent newsletter on cutaneous reactions. The article included about irrigation pipe associated electrocution could be useful to include in farm safety programs. The articles on Congenital Malformations and Childhood Lead Poisoning were taken from the MMWR 1981 Annual Summary. These articles contain information about patterns of occurrence of lead poisoning and birth defects which I think are very interesting. It is the trends over the years that are especially significant because they show how the incidence rates of problems are changing. The article on cytogenetic patterns in persons that live near Love Canal is something that should be of great interest due to the very recent emphasis being placed on dioxins. If you have any questions about any of these excerpts please contact me and I will be glad to provide you with more details.

I. TMRC (Theoretical Maximum Residue Contribution)

Dr. R.E. Ridesdale of ICI recently gave the following presentation at the last Annual IR-4 meeting in Washington D.C. It is the best explanation of the concept and its relation to pesticide residues that I have ever heard. It brings up many points that relate to the perception of the toxicological significance of chemical residues in foods, feeds and fiber.

"...I was asked to comment on the TMRC (Theoretical Maximum Residue Contribution) and its relationship to ADI and to IR-4 petitions specifically. First, I would like to give some definitions.

Allowable Daily Intake (ADI) - the daily exposure level which during lifetime appears to be without appreciable risk. Obtained by dividing the NOEL obtained in a chronic feeding study by a safety factor.

Example: NOEL = 5 mg/kg

Safety factor = 100

ADI = .05 mg/kg

Applied to a 60 kg person = 3 mg/day

Food Factor - the percent of the total diet of an average consumer made up by a food or class of foods.

Examples: cotton 0.15%, soybeans 0.92%, lettuce 1.31%, eggplant 0.03%, pears 0.26%, onions 0.83%

TMRC - obtained by multiplying the tolerance levels for raw agricultural commodities times the food factor for each commodity times an average diet of 1.5 kg.

Example: cotton tolerance level = 0.5 ppm, 0.5 mg/kg x 0.15% x 1.5 kg = 0.001 mg

With the above ADI figure of 3 mg/day, this TMRC would be only 0.03% of the ADI.

EPA is extremely conservative in estimating the TMRC, which is an upper limit on the estimated dietary intake. One has to consider that safety factor upon safety factor are already built into the ADI and into the tolerance. For example: a safety factor of 100 over the NOEL is used in calculating the ADI. In setting the tolerance, it is assumed that (1) all of the crop in the U.S. is treated, (2) at the maximum dosage rate, (3) for the maximum number of applications, and that (4) the maximum observed residue is always present. According to EPA, the fact that the TMRC is at or above the ADI is not a problem in itself--it means that EPA needs to look at a realistic case as opposed to the worst case. In the realistic case, the reexamination of the residue data includes the following:

II. Carbon Monoxide Intoxication - A Preventable Environmental Health Hazard

Each year in the United States, an estimated 10,000 persons seek medical attention or lose at least one day of normal activity because of carbon monoxide (CO) intoxication; at least 1,500 persons die from accidental exposure to high concentrations of CO; and approximately 2,300 persons commit suicide with CO. In addition to acute CO poisoning resulting in death, considerable danger may result from daily exposure to low concentrations of CO in houses, work places, and schools. Prolonged periods of exposure may cause headache, dizziness, and sleepiness. Continued exposure brings on nausea, vomiting, heart palpitations, and, from exposure to high levels of CO for prolonged periods, unconsciousness and death.

In 1980, the Consumer Product Safety Commission estimated 7.6 million unvented gas space heaters were in use; CO from such heaters caused approximately 70 deaths in 1980.

Numerous studies have demonstrated the seriousness of the CO problem. In 1975, a study to determine usual CO levels during a non-summer month in 80 urban and rural households in Fort Collins, Colorado, showed that 6% of the homes had CO concentrations at or above 10 parts per million (ppm)*, and one had 30 ppm CO in the kitchen and family room. A socioeconomic gradient was found; homes in low socioeconomic areas had the highest CO levels. There was no statistical difference between CO levels in urban and rural housing.

In the mid-1970's, the Allegheny County Health Department, Pittsburgh, Pennsylvania, conducted an investigation and found that 58% of the 33 CO fatalities during a 7-year period were located in low socioeconomic areas. In an effort to reduce these fatalities, the county health department conducted a multi-phase CO-reduction program consisting of public education, action (including distribution of CO dosimeters to and inspections of housing units), and evaluations. This prevention program resulted in a zero CO-fatality rate for the first winter in 8 years.

Other studies indicate that CO contamination is not limited to buildings. In 1975, the U.S. Department of Transportation demonstrated that a substantial number of school children and bus drivers may be exposed to harmful levels of CO from school buses. No deaths occurred, but many instances of headache, nausea and nonspecific illness were reported.

Editorial Note: CO is a common and lethal gas produced by the incomplete combustion of a solid, liquid, or gaseous fuel and is increased by inadequate air-fuel mixture, insufficient ventilation of combustion gases, and insufficient fresh air intake. It is odorless, colorless, tasteless, and non-irritating, but is often found combined with other gases that may produce a sharp odor and irritate the eyes. CO is absorbed only through the lungs; toxicity occurs when the gas combines with hemoglobin to form carboxyhemoglobin (COHb). Carbon monoxide- bound hemoglobin is unavailable to transport oxygen. Until CO enters the erythrocytes, it behaves like oxygen. When it contacts the erythrocytes, however, its behavior differs sharply; CO affinity for hemoglobin is approximately 210 times greater than that of oxygen. Death can occur when blood contains from 60% to 80% COHb.

*(Environmental Protection Agency (EPA) standards for CO are identified at levels of 9 ppm, 8-hour exposure, and 35 ppm, 1- hour exposure, neither to be exceeded more than once per year. EPA is currently considering revisions of these standards.) The following guidelines summarize the most important techniques for prevention of CO poisoning.

  1. Provide adequate ventilation when using wood stoves and fireplaces, and ensure that all flame-burning appliances are properly installed, adjusted, and operated. Ovens and gas ranges should not be used for heating purposes.
  2. Do not operate gasoline-powered engines (automobiles, lawnmowers, etc.) in confined spaces (such as garages or basements).
  3. Never burn charcoal inside a home, cabin, recreational vehicle, or tent, whether in a grill, hibachi pot, or fireplace, for cooking or heating.
  4. Have only a qualified technician install or convert fuel-burning equipment from one type of fuel to another.

MMWR - October 8, 1982/Vol. 31/No. 39

III. Dermatitis Associated with Cashew Nut Consumption - Pennsylvania

During April 1982, a poison ivy-like dermatitis affected 54 persons who consumed cashew nut pieces sold by a Little League organization in a southcentral Pennsylvania community. The cashew pieces, sold in 7-oz. bags, were imported from Mozambique and processed for distribution by a Pittsburgh company. The Little League had purchased 2,928 bags from a local distributor, and another 4,512 bags were sold by a distributor in small quantities throughout south-central Pennsylvania and northern Maryland.

Of 322 people interviewed who had purchased cashews from the Little League, 54 (20%) of 274 who ate cashews developed pruritic rash; none of the 48 who did not eat cashews developed rash (p <0.01).

Fourteen bags of cashews were opened and visually inspected; five (36%) contained pieces of cashew shell. The absence of cashew shell from 2/3 of the bags may account for the lack of correlation between patch-testing results and clinical illness.

Editorial Note: The cashew tree, Anacardium occidentale, belongs to the same family of plants (Anacardiaceae) as the Rhus species, which cause poison ivy, poison oak, and poison sumac. This tree bears a pear-shaped fruit called the cashew apple. On the distal end of the fruit is the cashew nut, which is not encased in the pulp of the fruit. It is composed of an inner kernel and a double layered outer shell. Between the layers of shell is an oil containing 12 chemically distinct antigens, including cardol and anacardic acid, which are immunochemically related to the pentadecylcatechols found in the Rhus species. These oils have irritant and allergenic properties. Cashew nuts are partially processed before importation into the United States to remove shells and oil, and then cooked and packaged before distribution. Pruritic dermatitis is a common problem among workers who shell the nuts by hand. Modern processing equipment has reduced the frequency of dermatitis among workers, and has increased the efficiency of oil extraction from cashew nuts. This report documents what may be the largest outbreak of cashew nut-related dermatitis among persons not working directly with the raw nut or its oil.

Hypersensitivity to Rhus antigens appears to overlap hypersensitivity to cashew nut oil allergens, and hence, incompletely processed cashew nuts may pose a health risk to persons sensitive to poison ivy, poison oak, or poison sumac.

MMWR - March 11, 1983/Vol. 32/No. 9

IV. Irrigation-Pipe-Associated Electrocution Deaths - Washington

Analysis showed that farmers are significantly more likely than non-farmers to die of accidental electrocution.

Even when electrical lines fully meet this requirement, workers may contact electrical lines when tilting irrigation pipes upwards to empty them of water, dirt, or small animals. During 1950-1979, 42 Washington farmers were recorded as havingdied from electrocution; based on overall mortality for the age and sex group involved, only 18 deaths from electrocution would have been expected. IPA electrocutions accounted for 23 (53%) of the 42 deaths recorded among farmers in general and among specific classifications of agricultural workers.

Editorial Note: In Washington, irrigation pipes have been the most common source of all fatal human contact with electrical lines. From 1970 to 1979, IPA electrocutions accounted for 20% of all electrocutions.

MMWR - April 8, 1983/Vol. 32/No. 13

V. Congenital Malformations

Number of monitored total (live and still) births by U.S. Census Region

Region 1980 1979 1978 1977 1976
Northeast 120,324 174,435 179,414 207,049 209,277
North Central 306,371 405,577 369,350 406,662 385,877
South 208,088 263,360 244,515 274,169 265,680
West 134,959 186,898 180,872 189,210 188,964
TOTAL US 769,742 1,030,270 974,151 1,077,090 1,049,798


The birth defects data reported here are selected from those collected through the Birth Defects Monitoring Program (BDMP) which is conducted by CDC with data provided under contract by the Commission on Professional and Hospital Activities (CPHA). The primary purpose of this program is to monitor the incidence of birth defects and other conditions in neonates. Since 1970, data on births of 11 million infants have been included in the BDMP. The current annual number of births covered, from 955 hospitals, is 770,000 - about 21% of the births in the United States. For the period covered in this report, the incidence of the majority of birth defects neither substantially increased nor decreased. Several defects, however, did show noteworthy patterns.

Anencephaly (the absence or severe reduction in size of the brain and absence of the cranial vault) incidence decreased about 21% between 1976 and 1980. This decrease is a continuation of the pattern in anencephaly rates seen in BDMP since 1970, the earliest year for which these data are available. The previously established trend of decreasing rates of spina bifida (failure of developing vertebrae to fuse at the middle of the back thus resulting in an unprotected spinal cord), however, seems to have stabilized. The reasons for these changes are not known. Two heart defects, ventricular septal defect (VSD) and patent ductus (PDA), increased greatly from 1976-1980. ( Author note: VSDs are usually holes in the wall separating the ventricles that allow oxygenated and unoxygenated blood to mix. This may result in a "blue" baby. The ductus arteriosus is a small vessel that joins the aorta and the pulmonary artery. This allows a bypass around the lungs for embryonic blood since in utero the childs blood gets oxygen from the maternal circulation via the placenta. At birth, chemicals are usually released that cause the ductus arteriosus to close. If the ductus does not close, a "blue" baby is the result.) Rates of these malformations rose over 38% during the 4-year interval and they have tripled since 1970. The increase in PDA rates is thought to be at least partly due to an increased survival of very low birth-weight babies and to better case ascertainment. On the other hand, the increase in VSD rates more likely reflects a true increase. A follow-up study in Atlanta, Georgia, showed that the spontaneous closure rates at 1 year of age did not change between 1970 and 1976. This suggests that the increase in VSD rates is not explained by better reporting of less severe cases which, in turn, suggests that the overall level of ascertainment has not changed materially.

VI. Lead Poisoning

For 1981, 62 childhood lead-poisoning prevention programs reported the screening of over 500,000 children for lead toxicity. Of the children screened, over 18,000 (3.6%) were identified who had lead toxicity and required medical care and environmental intervention to identify and reduce their sources of lead exposure.

Childhood lead toxicity is found throughout the United States in large and small communities. This has been documented by screening results over the last 10 years, which report almost 4 million children being tested and 247,000 identified with lead toxicity. In addition, the Second National Health and Nutrition Examination Survey, 1976-1980 (NHANES II)- done by the National Center for Health Statistics to measure blood lead levels in the general United States population - found that 4% of children, ages 6 months to 5 years, had elevated blood lead levels (>29 ug of lead/dl of whole blood). The geographic distribution of these elevated blood findings were as follows: children from inner cities of large urban areas, 11.6%; children from smaller urban areas, 3.5%; and children in rural areas, 2.1%.

Children are exposed to lead from many sources - food, air, water, dust, soil, and paint. Lead-base paint is usually the single most important source of lead for the severely poisoned child, but other sources also contribute to the child's total body-lead burden. For example, lead contained in air, dust, and soil may constitute a hazard for children. The decrease in mean blood lead level, documented by NHANES II, correlates remarkably well with the reduction in the amount of lead used in gasoline production; lead residue from motor vehicle gasoline combustion is a major contributor to total lead in air, dust, and soil. NHANES II also found that there has been a gradual decrease in the mean blood lead level of the overall population between 1976 and 1980. Although this decrease does not mean that the problem of childhood lead toxicity has been solved, it does mean that children living in environments with high-dose sources of lead (e.g., lead-base paint, lead deposits in dust and soil) now have a greater margin of safety because of the decrease in lead residue from motor vehicle gasoline combustion.

MMWR - Annual Summary, 1981 - October 1982/Vol. 30/No. 54

VII. Cytogenetic Patterns in Persons Living Near Love Canal - New York

Residents and former residents of the area surrounding Love Canal, a former dump site for chemical wastes of Niagara Falls, New York, were recently studied for cytogenetic changes. Frequencies of chromosomal aberrations and/or sister chromatid exchange (SCE) were measured in peripheral blood specimens obtained between December 1981 and February 1982 from 46 persons. Blind analyses were performed with 44 matched control specimens from persons living in another part of Niagara Falls. Two sets of Love Canal participants were included. The first group consisted of 29 persons who, in 1978, lived in seven of 12 homes, directly adjoining the canal, in which air, water, and soil testing showed elevated levels of chemicals spreading from the canal. The second group included 17 persons in whom cytogenetic analyses had been performed in 1980 as part of a pilot investigation supported by the U.S. Environmental Protection Agency.

In neither group did frequencies of SCE or chromosomal aberrations (such as gaps, breaks, fragments, or supernumerary acentrics) differ significantly from control levels. Karyotypes were normal in all specimens. In assessing chromosome damage, several factors of interest - sex, cigarette smoking, history of playing on the canal site, and history of attending an elementary school that adjoined the site - were examined as possible causes of cytogenetic variation. History of current cigarette smoking was significantly associated with increased SCE frequency, a result observed independently in studies elsewhere. Other factors, alone or in combination, were not associated with any significant increase in chromosome damage.

Editorial Note: In May 1980, results of an earlier cytogenetic study led to concern that chromosome damage might be increased among residents of the Love Canal area. Results of the present study do not support this conclusion and indicate instead that chromosome alteration frequencies are the same in Love Canal residents as in residents elsewhere in Niagara Falls.

Interpretation of these findings are limited by 1) considerable passage of time since 1978 when homes adjoining the canal were evacuated and corrective drainage work began at the site, and 2) lack of objective measurements for canal-related chemical exposures in individual residents. Although cytogenetic changes in peripheral blood lymphocytes are known to persist for years after exposure to ionizing radiation, similar persistence after chemical exposures may not necessarily occur.

Cytogenetic studies may prove useful in the future in assessing subclinical toxic damage in situations where tests can be done at the time of exposure or soon after, and where individual exposure can be reliably measured. Present experience, however, suggests that, while cytogenetic measurements of this sort may provide good correlations with doses of radiation or toxin, their predictive value for future individual health is quite uncertain.

MMWR - May 27, 1983/Vol. 32/No. 20

Arthur L. Craigmill, Ph.D.
Extension Toxicologist
U.C. Davis