Figure 1
Glyphosate
glyphosate
N-(phosphonomethyl)glycine
isopropylamine salt of
glyphosate
[More on Monsanto and its products]
Caroline Cox is JPR's editor.
Figure 1
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isopropylamine salt of
glyphosate |
Glyphosate is a broad-spectrum herbicide widely used to kill unwanted plants both in agriculture and in nonagricultural landscapes. Estimated use in the U.S. is between 38 and 48 million pounds per year. Most glyphosate-containing products are either made or used with a surfactant, chemicals that help glyphosate to penetrate plant cells.
Glyphosate-containing products are acutely toxic to animals, including humans. Symptoms include eye and skin irritation, headache, nausea, numbness, elevated blood pressure, and heart palpitations. The surfactant used in a common glyphosate product (Roundup) is more acutely toxic than glyphosate itself the combination of the two is yet more toxic.
Given the marketing of glyphosate herbicides as benign, it is striking that laboratory studies have found adverse effects in all standard categories of laboratory toxicology testing. These include medium-term toxicity (salivary gland lesions), long-term toxicity (inflamed stomach linings), genetic damage (in human blood cells), effects on reproduction (reduced sperm counts in rats; increased frequency of abnormal sperm in rabbits), and carcinogenicity (increased frequency of liver tumors in male rats and thyroid cancer in female rats).
In studies of people (mostly farmers) exposed to glyphosate herbicides, exposure is associated with an increased risk of miscarriages, premature birth, and the cancer non-Hodgkin's lymphoma.
Glyphosate has been called "extremely persistent" by the U.S. Environmental Protection Agency, and half lives of over 100 days have been measured in field tests in Iowa and New York. Glyphosate has been found in streams following agricultural, urban, and forestry applications.
Glyphosate treatment has reduced populations of beneficial insects, birds, and small mammals by destroying vegetation on which they depend for food and shelter.
In laboratory tests, glyphosate increased plants' susceptibility to disease and reduced the growth of nitrogen-fixing bacteria.
Glyphosate, N-(phosphonomethyl) glycine (Figure 1), is a systemic and nonselective herbicide used to kill broadleaved, grass, and sedge species.2 It has been registered in the U.S. since 1974 and is used to control weeds in a wide variety of agricultural, urban, lawn and garden, aquatic, and forestry situations.3 Most glyphosate herbicides contain the isopropylamine salt of glyphosate.4
Glyphosate products are manufactured by Monsanto Company worldwide. They are marketed under a variety of trade names: Roundup, Rodeo, and Accord are the most common names in the US.2
Unlike most other herbicides, chemicals which are closely related to glyphosate are not effective herbicides.'
In the U.S., 25 million applications are made yearly on lawns and in yards. 9
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Types of Use
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TOXICOLOGY OF
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Two of the three aromatic amino acids are essential amino acids in the human diet because humans, like all higher animals, lack the shikimic acid pathway, cannot synthesize these amino acids, and rely on their foods to provide these compounds. One is synthesized in animals through another pathway.11
Glyphosate can affect plant enzymes not connected with the shikimic acid pathway. In sugar cane, it reduces the activity of one of the enzymes involved in sugar metabolism.12 It also inhibits a major detoxification enzyme in plants.13
Roundup affects enzymes found in mammals. In rats, Roundup decreased the activity of two detoxification enzymes in the liver and an intestinal enzyme.14
In the case of glyphosate products, many "inerts" have been identified. See "Toxicology of `Inert' Ingredients of Glyphosate-containing Products," (at right), for basic information about these "inerts."
Many of the toxicology studies that will be summarized in this factsheet have been conducted using glyphosate, the active ingredient, alone. Some have been conducted with commercial products containing glyphosate and "inert" ingredients. When no testing is done with the product as it is actually used, it is impossible to accurately assess its hazards.
We will discuss both types of studies, and will identify insofar as is possible what material was used in each study.
Commercial glyphosate herbicides are more acutely toxic than glyphosate. The amount of Roundup (containing glyphosate and the surfactant POEA) required to kill rats is about 1/3 the amount of glyphosate alone.' Roundup is also more acutely toxic than POEA.15
Glyphosate-containing products are more toxic via inhalation than orally. Inhalation of Roundup by rats caused "signs of toxicity in all test groups," 16 even at the lowest concentration tested. These signs included gasping, congested eyes, reduced activity," and body weight loss.16 Lungs were red or blood-congested.17 The dose required to cause lung damage and mortality following pulmonary administration of two Roundup products and POEA (when forced into the trachea, the tube carrying air into the lungs) was only 1/10 the dose causing damage orally.15, 18
Effects on the Circulatory System: When dogs were given intravenous injections of glyphosate, POEA, or Roundup so that blood concentrations were approximately those found in humans who ingested glyphosate, glyphosate increased the ability of the heart muscle to contract. POEA reduced the output of the heart and the pressure in the arteries. Roundup caused cardiac depression.19
Eye Irritation: NCAP surveyed eye hazards listed on material safety data sheets for 25 glyphosate-containing products. One of the products is "severely irritating," 20 four cause "substantial but temporary eye injury," 21-24 eight "cause eye irritation," 25-32 five "may cause eye irritation," 33-37 one is "moderately irritating," 38 and three are "slightly irritating." 39-41 The other three products require addition of a surfactant (wetting agent) before use,42-44 and the surfactant sold by glyphosate's manufacturer for this purpose "causes eye burns." 45
Skin Irritation: Glyphosate is classified as a slightly irritating to skin. Roundup is a "moderate skin irritant," and recovery can take over two weeks.16
| eye irritation painful eyes burning eyes blurred vision swollen eye, face, joints |
blisters skin rash rapid heartbeat heart palpitations elevated blood pressure |
chest pains congestion coughing headache nausea |
facial numbness burning sensation on skin itchy skin tingling skin recurrent eczema |
Temple, W.A. and N.A. Smith. 1992. Glyphosate herbicide poisoning experience in New Zealand. N.Z. Med. J. 105:173-174.
Calif. EPA. Dept. of Pesticide Regulation. 1998. Case reports received by the California Pesticide Illness Surveillance Program in which health effects were attributed to glyphosate, 1993-1995. Unpublished report.
Smaller amounts of Roundup cause adverse effects, usually skin or eye irritation as well as some of the symptoms listed above. (See Table 1.) For example, rubbing of Roundup in an eye caused eye and lid swelling, rapid heartbeat and elevated blood pressure. Wiping the face after touching leaky spray equipment caused swelling of the face. Accidental drenching with horticultural Roundup caused eczema of the hands and arms lasting two months.63 A spill resulted in dizziness, fever, nausea, palpitations, and sore throat.72
Figure 3
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The NTP study also found increases in two liver enzymes at all but the two lowest doses tested. Other effects found in at least two doses in this study were reduced weight gain in rats and mice; diarrhea in rats; and changes in kidney and liver weights in male rats and mice.74
Another subchronic laboratory test found that blood levels of potassium and phosphorus in rats increased at all doses tested (60-1600 mg/kg/day).4
Glyphosate-containing products are more toxic than glyphosate in subchronic tests. In a 7 day study with calves, 790 mg/kg per day of Roundup caused pneumonia, and death of 1/3 of the animals tested. At lower doses decreased food intake and diarrhea were observed.2
The publicly available laboratory studies of glyphosate's ability to cause cancer were all conducted by or for its manufacturer.2 The first carcinogenicity study submitted to EPA (1981) found an increase in testicular tumors in male rats at the highest dose tested as well as an increase in the frequency of a thyroid cancer in females. Both results occurred at the highest dose tested (30 mg/kg of body weight per day). 75, 76 The second study (1983) found an increasing trend in the frequency of a rare kidney tumor in male mice.77 The most recent study (1990) found an increase in pancreas and liver tumors in male rats together with an increase of the same thyroid cancer found in the 1983 study in females.78
All of these increases in tumor or cancer incidence are "not considered compound-related" 78 according to EPA (This means that EPA did not consider glyphosate the cause of the tumors.) For the testicular tumors, EPA accepted the interpretation of an industry pathologist who said that the incidence in treated groups (12 percent) was similar to those observed (4.5 percent) in other rats not fed glyphosate.78 For the thyroid cancer, EPA stated that it was not possible to distinguish between cancers and tumors of this type, so that the two should be considered together. The combined data are not statistically significant.76 For the kidney tumors, the manufacturer reexamined the tissue and found an additional tumor in untreated mice so that statistical significance was lost. This was despite the opinion of EPA's pathologist that the lesion in question was not really a tumor.77 For the pancreatic tumors, EPA stated that there was no dose-related trend. For the liver and thyroid tumors, EPA stated that pairwise comparisons between treated and untreated animals were not statistically significant.78
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Peluso, M. et al. 1998. 32P-Postlabeling detection of DNA adducts in mice treated with the herbicide Roundup. Environ. Molec. Mutag.31:55-59. |
Bolognesi, C. et al. 1997. Genotoxic activity of glyphosate and its technical formulation Roundup. J. Agric. Food Chem. 45:1957-1962. |
| Roundup causes genetic damage in
laboratory animals and in human blood
cells. | |
There are no publicly available laboratory studies of the carcinogenicity of Roundup or other glyphosate-containing products.
In fruit flies, Roundup and Pondmaster (an aquatic herbicide consisting of glyphosate and a trade secret surfactant82) both increased the frequency of sexlinked, recessive lethal mutations. (These are mutations that are usually visible only in males. Only a single concentration was tested in this study .83
A study of human lymphocytes (a type of white blood cell showed an increase in the frequency of sister chromatid exchanges following exposure to the lowest dose tested of Roundup.84 (Sister chromatid exchanges are exchanges of genetic material during cell division between members of a chromosome pair. They result from point mutations.) A 1997 study of human lymphocytes (see Figure 4) found similar results with Roundup (at both doses tested and with glyphosate (at all but the lowest dose tested).81
In Salmonella bacteria, Roundup was weakly mutagenic at two concentrations. In onion root cells, Roundup caused an increase in chromosome aberrations, also at two concentrations. 85
In mice injected with Roundup, the frequency of DNA adducts (the binding to genetic material of reactive molecules that lead to mutations) in the liver and kidney increased at all three doses tested.86 (See Figure 4.)
In another study of mice injected with glyphosate and Roundup, the frequency of chromosome damage and DNA damage increased in bone marrow, liver, and kidney. (Only a single concentration was tested in this study.) 81
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img border = "0" src="/Roundup-Glyphosate-Factsheet-CoxF5a.GIF" width="400" height="173">
U.S. Dept. of Health and Human Services. Public Health Serv. National Inst. Health. 1992. NTP technical report on toxicity studies of glyphosate (CAS No. 1071-83-6) administered in dosed feed to F344/N rats and B6C3Fl mice. Research Triangle Park, NC: National Toxicology Program. |
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Savitz, D.A. et al. 1997. Male pesticide exposure and pregnancy outcome. Am. J. Epidemiol. 146:1025-1036. Glyphosate exposure is associated with
reproductive problems in both laboratory animals and
farmers. |
In rats, glyphosate reduced sperm counts at the two highest doses tested. (See Figure 5.) In male rabbits, glyphosate at doses of 1/10 and 1/100 of the LD50 increased the frequency of abnormal and dead sperm.89
Using cells taken from Leydig cell testicular tumors in mice, researchers from Texas Tech University showed that exposure to Roundup (but not glyphosate alone caused a decrease in the production of sex hormones. Specifically, Roundup inhibited the expression of a protein that carries cholesterol (the molecule from which sex hormones are made to the site where these hormones are synthesized. Lacking necessary amounts of cholesterol, the testicle cells' production of sex hormones decreased about 90 percent.89a
In a study of female rabbits, glyphosate caused a decrease in fetal weight in all treated groups.90
Laboratory fraud first made headlines in 1983 when EPA publicly announced that a 1976 audit had discovered "serious deficiencies and improprieties" in studies conducted by Industrial Biotest Laboratories (IBT)." Problems included "countless deaths of rats and mice" and "routine falsification of data."91
IBT was one of the largest laboratories performing tests in support of pesticide registrations.91 About 30 tests on glyphosate and glyphosate-containing products were performed by IBT, including 11 of the 19 chronic toxicology studies.92 A compelling example of the poor quality of IBT data comes from an EPA toxicologist who wrote, "It is also somewhat difficult not to doubt the scientific integrity of a study when the IBT stated that it took specimens from the uteri (of male rabbits for histopathological examination."93 (Emphasis added.)
In 1991, EPA alleged that Craven Laboratories, a company that performed studies for 262 pesticide companies including Monsanto, had falsified tests.94 "Tricks" employed by Craven Labs included "falsifying laboratory notebook entries" and "manually manipulating scientific equipment to produce false reports."95 Roundup residue studies on plums, potatoes, grapes, and sugarbeets were among the tests in question.96
The following year, the owner of Craven Labs and three employees were indicted on 20 felony counts.97 The owner was sentenced to five years in prison and fined $50,000; Craven Labs was fined 15.5 million dollars, and ordered to pay 3.7 million dollars in restitution.95
Although the tests of glyphosate identified as fraudulent have been replaced, this fraud casts shadows on the entire pesticide registration process.
In 1998, Monsanto Co. negotiated a similar agreement with the New York attorney-general about a different advertisement. The attorney general found that the advertisement featuring a horticulturist from the San Diego Zoo also was "false and misleading" because it implied to consumers that Roundup could be used (contrary to label directions) in and around water.98a Monsanto paid $75,000 in costs.98a
EPA made a similar determination about Roundup ads in 1998, finding that they contained "false and misleading"98 claims and were in violation of FIFRA. However, EPA took no action and did not even notify Monsanto Co. about the determination because two years had elapsed between the time that the ads were submitted to EPA and the time that EPA made the determination99
For this reason, it is not included in government monitoring of pesticide residues in food.2 The only information available about contamination of food comes from research studies." Glyphosate's manufacturer reported that drift from a ground application in Minnesota damaged 25 acres of corn, and the Washington Department of Agriculture reported damage to 30 acres of onions from a ground application of a glyphosate herbicide."
Monsanto's studies of residues in food crops found glyphosate in lettuce over five months after treatment (the lettuce was planted four months after treatment). Monsanto also found glyphosate in barley over four months after treatment (the barley was planted one month after treatment) .90a
"Significant residues,"2 according to the World Health Organization, have been identified from pre-harvest use of glyphosate on wheat (to dry out the grain). Bran contains between 2 and 4 times the amount on whole grains. Residues are not lost during baking.2
While many of the California reports involve "irritant effects," 102 mostly to the eyes and skin, NCAP's survey of about 100 reports made in 1993, 1994, and 1995 found that over half of them involved more serious effects: burning of eyes or skin, blurred vision, peeling of skin, nausea, headache, vomiting, diarrhea, chest pain, dizziness, numbness, burning of the genitals, and wheezing.103
Other occupational symptoms were observed in a flax milling operation in Great Britain. A study compared the effects of breathing dust from flax treated with Roundup with the effects of dust from untreated flax. Treated dust caused a decrease in lung function and an increase in coughing, and breathlessness. 104
A simple answer to the question, "How far can I expect glyphosate to travel off site?" is difficult, since drift is "notoriously variable."108 However, extensive drift of glyphosate has been measured since the 1970s when a California study found glyphosate 800 m (2600 feet) from aerial and ground applications. Similar drift distances were found for the 8 different spray systems tested in this study.109
Drift distances that have been measured more recently for the major application techniques include the following:
Ground Applications: A study of 15 noncrop plants found seedling mortality (killing about 10 percent of seedlings) for most of the species tested at 20 meters (66 feet) downwind when using a tractor-mounted sprayer. Seedlings of some sensitive species were killed at 40 meters (131 feet).110 A drift model predicted some native species would be damaged at distances of 80 meters (262 feet).107 Glyphosate's manufacturer reported that drift from a ground application in Minnesota damaged 25 acres of corn,111 and the Washington Department of Agriculture reported damage to 30 acres of onions from a ground application of a glyphosate herbicide.112
Helicopter applications: A study done in Canada113 measured glyphosate residues 200 meters (656 feet) from target areas following helicopter applications to forest sites. In this study, 200 meters was the farthest distance at which samples were taken, so the longest distance glyphosate traveled is not known.Fixed-wing aircraft: Long drift distances occur following applications of glyphosate made from airplanes. Two studies on forested sites conducted by Agriculture Canada (the Canadian agricultural ministry) showed that glyphosate was found at the farthest distance from the target areas that measurements were made (300 and 400 meters, or 984 and 1312 feet).114, 115 One of these studies115 calculated that buffer zones of between 75 and 1200 meters (246 feet - 0.75 miles) would be required to protect nontarget vegetation. According to Monsanto, drift from single aerial applications of glyphosate has been extensive enough to damage 1000 trees in one case,116 250 acres of corn in another,117 and 155 acres of tomatoes in a third incident.118
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Note: Numbers, as well as the length of the columns, give the half-life, in days, of glyphosate in soil. Half-life is the length of time required for half the applied glyphosate to break down or move out of the test site. Source: U.S. EPA. Environmental Fate and Effects Division. 1993. Pesticide environmental fate one line summary; Glyphosate. Washington, D.C., May 6. Glyphosate's persistence in soil varies widely, but its half-life in agricultural soil can be over 4 months. |
Glyphosate is thought to be "tightly complexed [bound] by most soils"127 and therefore "in most soils, glyphosate is essentially immobile."127 This means that the glyphosate will be unlikely to contaminate water or soil away from the application site. However, this binding to soil is "reversible." For example, one study found that glyphosate bound readily to four different soils. However, desorption, when glyphosate unbinds from soil particles, also occurred readily. In one soil, 80 percent of the added glyphosate desorbed in a two hour period. The study concluded that "this herbicide can be extensively mobile in the soil ...." 123
Glyphosate has been found in both ground and surface water. Examples include farm ponds in Ontario, Canada, contaminated by runoff from an agricultural treatment and a spill129; the runoff from a watersheds treated with Roundup during production of no-till corn and fescue130; contaminated surface water in the Netherlands'; seven U.S. wells (one in Texas, six in Virginia contaminated with glyphosate 131; contaminated forest streams in Oregon and Washington132, 133; contaminated streams near Puget Sound, Washington 134; and contaminated wells under electrical substations treated with glyphosate.135
Glyphosate's persistence in water is shorter than its persistence in soils. Two Canadian studies found glyphosate persisted 12 to 60 days in pond water.136,137 Glyphosate persists longer in pond sediments (mud at the bottom of a pond). For example, the half-life in pond sediments in a Missouri study was 120 days; persistence was over a year in pond sediments in Michigan and Oregon.4
Santillo, D.J., D.M. Leslie, and P.W. Brown. 1989. Responses of small mammals and habitat to glyphosate application on clearcuts. J. Wildl. Manage. 53(1):164-172. Glyphosate treatment reduced invertebrate and small mammal populations for up to 3 years. |
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Springer, J.A. and R.A.J. Gray. 1992. Effect of repeated low doses of biocides on the earthworm Aporrectodea caliginosa in laboratory culture. Soil Biol. Biochem. 24(12):1739-1744. Repeated applications of glyphosate reduce the growth of earthworms. |
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