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WORLD HEALTH ORGANIZATION

WHO/PCS/DS/96.91

ORGANISATION MONDIALE DE LA SANTE

Original: ENGLISH

FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS

Distr.: LIMITED

ORGANISATION DES NATIO NS UNIES POUR L'ALIMENTATION ET L'AGRICULTURE

Date of issue: July 1996

WHO/FAO DATA SHEETS ON PESTICIDES

No. 91

GLYPHOSATE

1.0 GENERAL INFORMATION
1.1 Common Name:
1.1.1 Identity name:
1.2 Synopsis:
1.3 Selected Properties
1.3.1 Physical characteristics:
1.3.2 Solubility:
1.3.3 Stability:
1.3.4 Vapour pressure:
1.4 Agriculture, Horticulture And Forestry
1.4.1 Common formulations:
1.4.2 Pests controlled:
1.4.3 Use pattern:
1.4.4 Unintended effects:
1.5 Public Health Use
1.6 Household Use
2.0 TOXICOLOGY AND RISKS
2.1 Toxicology - Mammals
2.1.1 Absorption route:
2.1.2 Mode of action:
2.1.3 Excretion products:
2.1.4 Toxicity, single dose:
2.1.5 Toxicity, repeated dose:
2.1.6 Dietary studies:
2.1.7 Supplementary studies of toxicity:
2.1.8 Teratogenicity:
2.1.9 Mutagenicity:
2.1.10 Reproduction:
2.2 Toxicology - Man
2.2.1 Absorption route:
2.2.2 Dangerous doses:
2.2.3 Observations on occupationally exposed workers:
2.2.4 Observations on exposure of the general public:
2.2.5 Observations in volunteers:
2.2.6 Reported mishaps:
2.3 Toxicity To Non-Mammalian Species
2.3.1 Fish:
2.3.2 Birds:
2.3.3 Other species:
3.0 FOR REGULATORY AUTHORITIES -
RECOMMENDATIONS ON REGULATION OF COMPOUND
3.1 Recommended Restrictions On Availability
3.2 Transportation And Storage
3.3 Handling
3.4 Disposal And/Or Decontamination Of Containers
3.5 Selection, Training And Medical Supervision Of Workers
3.6 Additional Regulations Recommended If Distributed By Aircraft
3.7 Labelling
3.8 Residues In Food
4.0 PREVENTION OF POISONING IN
MAN AND EMERGENCY AID
4.1 Precautions In Use
4.1.1 General:
4.1.2 Manufacture and formulation - TLV:
4.1.3 Mixers and applicators:
4.1.4 Other associated workers (including flagmen in aerial operations):
4.1.5 Other populations likely to be affected:
4.2 Entry Of Persons Into Treatment Area
4.3 Decontamination Of Spillage And Containers
4.4 Emergency Aid
4.4.1 Early symptoms of poisoning:
4.4.2 Treatment before person is seen by physician, if symptoms appear following exposure:
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 Medical Diagnosis And Treatment In Cases Of Poisoning
5.1.1 General information:
5.1.2 Symptoms and signs:
5.1.3 Laboratory:
5.1.4 Treatment:
5.1.5 Prognosis:
5.1.6 References to previously reported cases:
5.2 Surveillance Tests
5.3 Laboratory Methods
5.3.1 Detection and Assay of Compound:
5.3.2 Other Tests in Case of Poisoning:

It must be noted that the issue of a Data Sheet for a particular pesticide does not imply endorsement of the pesticide by WHO or FAO for any particular use, or exclude its use for other purposes not stated. While the information provided is believed to be accurate according to data available at the time when the sheet was compiled, neither WHO nor FAO are responsible for any errors or omissions, or any consequences therefrom.

The issue of this document does not constitute formal publication. It should not be reviewed, abstracted or quoted without the agreement of the Food and Agriculture Organization of the United Nations or of the World Health Organization.

Ce document ne constitue pas une publication. Il ne doit faire l'objet d'aucun compte rendu ou résumé ni d'aucune citation sans l'autorisation de l'Organisation des Nations Unies pour l'Alimentation et l'Agriculture ou de l'Organisation Mondiale de la Santé.

CLASSIFICATION:

Primary use:

Herbicide

Secondary use:

 

Chemical group:

Organophosphonate

1.0 GENERAL INFORMATION

1.1 Common Name:

glyphosate (ANSI, BSI, E-ISO, F-ISO, JMAF, WSSA).

1.1.1 Identity name:

IUPAC name:

N-(phosphonomethyl)glycine

CAS name:

N-(phosphonomethyl)glycine

CAS registry number:

1071-83-6

 

38641-94-0 (mono(isopropylammonium) salt)

 

70393-85-0 (sesquisodium salt)

 

81591-81-3 (trimesium)

RTECS number:

MC 1075000

Molecular formula:

C3H8NO5P

Relative molecular mass:

169.01

Structural formula:

Structural Formula

Trade names: Armada; Dardo; Fuste; KleenupR; Landmester; MON-0573; PoledoR (sesquisodium); Quotemeter; Ranger; RodeoR; RoundupR (isopropyl ammonium); SpasorR; Squadron; StingR; Stirrup; TouchdownR (trimesium); TumbleweedR; Wellop.

1.2 Synopsis:

Glyphosate is a broad spectrum, post-emergent herbicide active by plant translocation. Glyphosate sesquisodium is used as a plant regulator on sugar cane. Soil residues generally have a half-life of less than 60 days. Glyphosate is an organophosphonate of low mammalian toxicity, which does not inhibit cholinesterase. Carrier solvents used in commercial formulations may change toxicological properties.

1.3 Selected Properties

1.3.1 Physical characteristics:

Pure glyphosate is a colourless, odourless, crystalline solid with a melting point of 185 ºC and decomposes at 187 ºC producing toxic fumes including nitrogen oxides and phosphorus oxides. Solutions of the glyphosate salts are corrosive to iron or galvanized steel.

1.3.2 Solubility:

Pure glyphosate is slightly soluble in water (12 g/litre at 25 ºC), and is practically insoluble in most organic solvents. The alkali-metal and amine salts are readily soluble in water.

1.3.3 Stability:

Glyphosate formulations are stable for extended periods below 60 ºC.

1.3.4 Vapour pressure:

<1 x 10-5 Pa at 25 ºC

1.4 Agriculture, Horticulture And Forestry

1.4.1 Common formulations:

Available as a water based solution of the glyphosate salt. RoundupR is the major formulation and contains 480 g mono (isopropylammonium) glyphosate/litre (equivalent to 360 g glyphosate/litre). Formulations might contain other active ingredients such as simasine, 2.4-D, or MCPA.

1.4.2 Pests controlled:

As a non-selective, post-emergent herbicide, glyphosate is very effective against deep rooted and woody perennials, annual and biennial grasses, sedges and broad leaved weeds.

1.4.3 Use pattern:

Glyphosate is used in both agriculture and forestry. It is also used for control of plants above the surface in aquatic environments, parks and road verges.

1.4.4 Unintended effects:

A herbicide of low selectivity. Not toxic to bees, birds and most aquatic organisms.

1.5 Public Health Use

No recommended usage reported.

1.6 Household Use

A formulation is available for household use.

2.0 TOXICOLOGY AND RISKS

2.1 Toxicology - Mammals

2.1.1 Absorption route:

After oral administration in rats, rabbits, laying hens and lactating goats, absorption of glyphosate from the gastrointestinal tract is 30-36%. Percutaneous absorption is about 5% of the administered dose in monkeys. In vitro absorption of glyphosate from excised human abdominal skin is less than 2%. No data on absorption through inhalation are available.

2.1.2 Mode of action:

In plants and some micro-organisms glyphosate inhibits the shikimic acid pathway, causing a deficit in aromatic amino acids. (Absence of this pathway may account for its low toxicity in animals). Acute effects in animals, following intraperitoneal administration of high doses, are suggestive of altered mitochondrial activity - possibly, uncoupling of oxidative phosphorylation.

2.1.3 Excretion products:

Glyphosate is excreted largely unchanged and the urine is the major route of excretion. Body clearance in rats is essentially complete 168 hours after administration.

2.1.4 Toxicity, single dose:

Glyphosate and herbicide formulation containing glyphosate have a very low oral and dermal acute toxicity. When given intraperitoneally the toxicity of glyphosate is markedly increased. In fact, the net oral LD50 of technical glyphosate is higher than 5000 mg/kg b.w. whereas that of formulations was found, in some instances, to be 1950-2510 mg/kg b.w. The dermal LD50 for glyphosate and formulation was always found to be >2000 mg/kg b.w. (possibly >5000). Intraperitoneal LD50 in mice and rats was 134-740 mg/kg b.w. Inhalation LC50 for RoundupR was 3180 mg/m3 in rats.

Ataxia, breathing difficulties and occasionally convulsions, preceded death in rats receiving lethal doses of glyphosate.

Primary irritation:

Glyphosate was irritating to rabbit eyes and slightly irritating to rabbit skin. The isopropylammonium salt (as RoundupR) was moderately irritating to rabbit eyes and to rabbit skin. Neither glyphosate nor its formulations (when tested) caused sensitization.

2.1.5 Toxicity, repeated dose:

Oral: The daily dose of 500 mg/kg b.w. given to dogs for one year did not cause adverse effects.

Inhalation: Rats were exposed to aerosols of a 1:3 dilution of a glyphosate formulation (Roundup) for 6 h/day, 5 days/week. The highest concentration corresponded to 0.12 mg/litre of the formulation. Only irritant effects on nasal turbinates, trachea and lungs were observed.

Dermal: Glyphosate technical, applied to intact or abraded skin of rabbits at 100, 1000 or 5000 mg/kg b.w./day for five days/week for three weeks, caused no observed signs of systemic poisoning. A slight degree of dermal irritation was observed at the application site of high dose group animals only.

In a 21-day dermal toxicity study using a formulated product containing undiluted formulation of glyphosate isopropylamine salt, no systemic adverse effects were observed at 76 or 114 mg/kg b.w. (5 days per week). Dermal irritation was observed which recovered within 4 weeks.

2.1.6 Dietary studies:

Several short-term dietary studies have been carried out in mice and rats. No adverse effects were observed in a 90-day study in mice at high doses up to 50,000 mg/kg diet (equal to 9710 mg/kg per day), highest dose tested, and in a 90-day study in rats at doses up to 20,000 mg/kg diet (equal to 1267 mg/kg per day), highest dose tested. Two studies conducted in mice and rats by NTP showed lesion of the salivary glands whose toxicological significance is unknown. These lesions were never found in other short- and long-term studies.

2.1.7 Supplementary studies of toxicity:

Long-term and carcinogenicity: Few toxic effects and no increased tumour incidence were observed in long-term feeding studies in both mice and rats. In mice, at 30,000 mg/kg diet, technical glyphosate caused growth retardation and hepatocyte hypertrophy or necrosis. The NOAEL was 5000 mg/kg diet (equal to 814 mg/kg b.w. per day). Similar effects were observed in rats at 20,000 mg/kg diet and the NOAEL was found to be 8000 mg/kg diet (equal to 410 mg/kg b.w. per day).

2.1.8 Teratogenicity:

Technical glyphosate was not found to be teratogenic in rats and rabbits at doses which caused maternal toxicity (3500 and 350 mg/kg b.w. per day, respectively).

2.1.9 Mutagenicity:

Glyphosate was not genotoxic in a range of in vitro and in vivo tests, except in a test for SCE in human lymphocytes at very high concentrations.

2.1.10 Reproduction:

Two dietary multigeneration studies were conducted in rats with technical glyphosate. Effects on parental and pup body weight were observed at 30,000 mg/kg diet (equivalent to 1500 mg/kg b.w. per day) with a NOAEL of 10,000 mg/kg diet (equivalent to 500 mg/kg b.w. per day).

2.2 Toxicology - Man

2.2.1 Absorption route:

Glyphosate may be absorbed from the gastrointestinal tract and through the skin. Animal data indicate about 30% absorption from the gastrointestinal tract. In vitro data indicate <2% absorption through the skin.

2.2.2 Dangerous doses:

Single: Many cases of acute intoxication (mainly suicide attempts) with herbicides containing glyphosate and sufactant (mainly Roundup) have been reported. Rough estimates of the amount ingested in the lethal cases varied from 85 to 200 ml (corresponding to roughly 30 to 70 g of glyphosate acid). However, larger amounts (up to 500 ml) were reported to have been ingested by patients with subsequent mild or moderate symptoms. It has been suggested that people over 40 years of age might be more sensitive to glyphosate toxicity. It has also been suggested that the toxic effect is due to the surfactant rather than to glyphosate in the commercial formulation; however, the evidence is as yet inconclusive.

Repeated: No information available.

2.2.3 Observations on occupationally exposed workers:

Symptoms resulting from dermal exposure incidental to the use of Roundup included periorbital oedema, and chemosis of the eye, with swelling at the site of contact and prolonged skin irritation.

No compound related effects were observed in five workers exposed for 1 week to glyphosate during silvicultural clearing with brush saws equipped with herbicide sprayers (air glyphosate concentration usually below 1.25 mg/litre). In these workers no glyphosate could be detected in urine. A number of exposure monitoring studies have been carried out. Maximal average exposure to glyphosate was estimated to be 8 mg/h. In most of the cases urinary glyphosate concentration was below detection limit.

2.2.4 Observations on exposure of the general public:

With good agricultural practice the general public should not be exposed to hazardous amounts of glyphosate.

2.2.5 Observations in volunteers:

Two dermal irritation studies were carried out with 0.9 ml of a 9:1 dilution of Roundup formulation in water or with 0.1 ml of the same undiluted formulation with both intact and abraded skin, respectively. Only some subjects with abraded skin showed erythema. A sensitization study gave negative results.

2.2.6 Reported mishaps:

Isolated incidents of dermal exposure, suicide attempts and accidental ingestion of dilute formulations have been reported. Where the poisoning could be positively attributed to glyphosate, the symptoms recorded were stomach cramps, diarrhoea, vomiting (associated with erosion of the gastrointestinal tract), and in the case of dermal exposure, skin irritation.

2.3 Toxicity To Non-Mammalian Species

2.3.1 Fish:

The toxicity test for fish are generally performed without sediment. As the bioavailability of glyphosate will be reduced by tripton on to sediments, no toxic effects are expected. Toxic effects, however, can be expected due to surfactants in some formulations. 4-day LC50 values range from 10 to >1000 mg/l for technical glyphosate.

2.3.2 Birds:

Glyphosate has low toxicity to birds after acute oral (LD50s > 3851 mg/kg b.w.) or short-term dietary (LC50s > 4650 mg/kg of feed) exposure.

2.3.3 Other species:

Glyphosate has low toxicity for bees, earthworms, microorganisms. Formulations are more toxic than technical glyphosate to aquatic invertebrates. LC50s and EC50s for crustaceans are 280 to >1000 and 5 to 1000 mg/litre, respectively.

3.0 FOR REGULATORY AUTHORITIES -
RECOMMENDATIONS ON REGULATION OF COMPOUND

3.1 Recommended Restrictions On Availability

[For definition of categories see the "Introduction to data sheets".]

No solid formulations to date: solid formulations <80% would be Category 5.

Liquid formulations of >21% (equivalent to >28% isopropylammonium salt) - Category 4.

Other formulations: Category 5.

3.2 Transportation And Storage

Formulations in category 4: Should be transported and stored in clearly labelled, rigid leak-proof containers made of stainless steel, aluminum, fibreglass, plastic or plastic lined steel. Do not mix, spray or store in galvanized or unlined steel containers. Storage should be under lock and key, secure from access by children and other unauthorized persons, and well away from food or drink.

Formulations in category 5: Should be transported and stored in clearly labelled, rigid leak-proof containers made of stainless steel, aluminum, fibreglass, plastic or plastic lined steel. Do not store in galvanized or unlined steel containers. Transportation and storage should be out of the reach of children and away from food and drink.

3.3 Handling

Formulations in category 4: Protective clothing (see 4.1.3-4.1.4) should be used by all persons handling the compound. Adequate washing facilities should be available at all times during handling and should be close to the site of handling. Eating, drinking and smoking should be prohibited during handling and before washing after handling.

Formulations in category 5: No facilities other than those needed for handling of any chemical required.

3.4 Disposal And/Or Decontamination Of Containers

Empty containers may be decontaminated but should not be used for transportation or storage of food or drink. Containers should be decontaminated by washing at least three times with detergent and large amounts of water and by scrubbing the sides. Impermeable gauntlets should be worn for these operations. Empty containers which are not decontaminated should be burned or crushed and buried below topsoil. Care must be taken to avoid contamination of water sources.

3.5 Selection, Training And Medical Supervision Of Workers

Formulations in category 4: A warning to workers to minimize contact is essential.

Formulations in category 5: A warning to workers to minimize contact is essential.

3.6 Additional Regulations Recommended If Distributed By Aircraft

All formulations: Pilots and loaders should have special training in application methods and in recognition of early symptoms of pesticide poisoning. Loaders must wear overalls, rubber gloves and goggles. Flagmen should additionally wear an impermeable, brimmed hat, and should be located well away from the dropping zone.

3.7 Labelling

Formulations in category 4 - minimum cautionary statement: Glyphosate is a herbicide which may be poisonous if swallowed. Skin and eye irritation may follow contact. Avoid all mouth and skin contact and the inhalation of aerosols generated during mixing or application procedures. Wash splashes from skin and eyes immediately. Wash hands and face before eating or smoking after handling the pesticide. Change clothing immediately after work. When handling concentrates wear protective gloves, goggles and clean protective clothing. Store away from food and out of the reach of children. Dispose of empty container safely. If poisoning occurs seek medical attention. Do not store or apply this product in galvanized steel or unlined steel (except stainless steel) containers or spray tanks.

Formulations in category 5 - minimum cautionary statement: This formulation contains glyphosate, a herbicide which may be poisonous if swallowed. Avoid all mouth, skin and eye contact. May be irritant to eyes and skin. Wash hands and face after use. Store in labelled container out of reach of children. Dispose of empty container safely. Do not store or apply this product in galvanized or unlined steel (except stainless steel) containers or spray tanks.

3.8 Residues In Food

Maximum residue limits (MRLs) have been proposed by FAO/WHO Joint Meeting on Pesticide Residues. The acceptable daily intake (ADI) has been set to 0-0.3 mg/kg b.w.

4.0 PREVENTION OF POISONING IN
MAN AND EMERGENCY AID

4.1 Precautions In Use

4.1.1 General:

Glyphosate is an organophosphonate of low toxicity and is without effect on cholinesterase activity. Absorption from the gastrointestinal tract occurs in laboratory animals and in the absence of quantitative data it must be assumed that absorption may occur from the skin, the lungs or gastrointestinal tract in man. Glyphosate salts are irritant to the skin and eyes.

4.1.2 Manufacture and formulation - TLV:

No published information available. Adequate ventilation must be provided to reduce exposure to this irritant compound.

4.1.3 Mixers and applicators:

When opening a container and when mixing, impermeable boots, clean overalls, gloves and goggles should be worn. Mixing, if mechanical, should always be carried out with a paddle of appropriate length. Do not mix, spray or store in galvanized or unlined steel containers. When spraying tall crops additional protective clothing should include a face mask and an impermeable hat. The applicator should avoid working in spray mist and avoid contact with the mouth. Splashes must be washed immediately from the skin, or eyes with large quantities of water. Before eating, drinking, or smoking, the face, hands and exposed skin should be thoroughly washed.

4.1.4 Other associated workers (including flagmen in aerial operations):

Persons exposed to the compound and associated with its application should wear protective clothing and observe the precautions described above in 4.1.3. under "Mixers and Applicators".

4.1.5 Other populations likely to be affected:

With good agricultural practice other persons should not be exposed to hazardous amounts of glyphosate.

4.2 Entry Of Persons Into Treatment Area

No re-entry guidelines established. Unprotected persons should be kept from the area until the application has dried to minimize the risk of irritant effects.

4.3 Decontamination Of Spillage And Containers

Residues in containers should be emptied in a diluted form into a deep pit, taking care to avoid contamination of ground waters. Decontamination of containers may be carried out according to Section 3.4, but decontaminated containers should not be used for transportation or storage of food and drink. Spillage of liquid formulations should be contained by absorbent material. This material should be burned or buried in a deep pit, taking care to avoid contamination of water sources. The remaining residues should be removed from the spillage site by washing with large quantities of water. Impermeable gloves should be used for all operations.

4.4 Emergency Aid

4.4.1 Early symptoms of poisoning:

Vomiting, nausea, diarrhoea and flu-like symptoms may accompany exposure to glyphosate. Reddening and irritation may accompany dermal or ocular exposures.

4.4.2 Treatment before person is seen by physician, if symptoms appear following exposure:

The person should stop work immediately, remove contaminated clothing; wash the affected skin areas with soap and water; and flush the skin or eyes with large quantities of water. If swallowed, vomiting should be induced if the person is fully conscious unless contraindicated by the solvent in the formulation.

5.0 FOR MEDICAL AND LABORATORY PERSONNEL

5.1 Medical Diagnosis And Treatment In Cases Of Poisoning

5.1.1 General information:

Glyphosate is an organophosphonate herbicide of low toxicity which does not inhibit cholinesterase activity. It may be absorbed from the gastrointestinal tract, skin or lungs. Glyphosate salts are irritant to the skin and eyes.

5.1.2 Symptoms and signs:

After ingestion, mild poisoning symptoms may include stomach cramps, vomiting, nausea and diarrhoea, and mouth and throat pain. Moderate poisoning is associated with gastrointestinal tract ulceration, hypotension, hepatic and renal damage. Severe poisoning is characterized by respiratory and renal failure, seizures, coma and eventually death. Dermal and conjunctival irritation may follow topical exposures.

5.1.3 Laboratory:

Direct measurement of glyphosate in the blood or in the urine will confirm exposure.

5.1.4 Treatment:

Treatment is symptomatic. Rapid gastric lavage should be performed using 5% sodium bicarbonate. Activated charcoal should be given to reduce absorption of remaining residues.

Following skin contamination, the affected area should be washed with soap and water. If the compound has entered the eyes they should be washed with isotonic saline or sterile water.

5.1.5 Prognosis:

The acute toxicity is low and the prognosis for a complete recovery is good although cases of death have been reported after suicidal attempt.

5.1.6 References to previously reported cases:

Brief medical summaries of 100 incidents of glyphosate exposures in the U.S. are published:

5.2 Surveillance Tests

There are no readily available field techniques to determine the degree of exposure.

5.3 Laboratory Methods

5.3.1 Detection and Assay of Compound:

AOAC Methods, 1990, 913.10

CIPAC Handbook, 1985, 1C, 2130

Pest. Anal. Manual, 1979, II.

5.3.2 Other Tests in Case of Poisoning:

None.

Several methods for determination of glyphosate in different matrices (air, plants, water, soil, urine, serum) have been described. These include extraction, clean-up and derivatisation. Analysis is then carried out by TLC, calorimetry, differential pulse polarography, GC, HPLC and 31pNMR.

REFERENCES

EPA (1980), Summary of Reported Pesticide Incidents Involving Glyphosate (Isopropylamine salt). Pesticide Incident Monitoring System. Report No. 373. Office of Pesticide Programs. USEPA.

FAO/WHO (1987), Pesticide Residues in Food - 1986 Evaluations, Part II - Toxicology, FAO Plant Production and Protection Paper 78/2, Rome, Food and Agriculture Organization of the United Nations.

The Pesticide Manual, A World Compendium (10th edition 1994), Tomlin, C., ed., British Crop Protection Council, 20 Bridport Road, Thornton Heath, CR4 7QG, U.K.

WHO (1994), Environmental Health Criteria No. 159, Glyphosate. UNEP/ILO/WHO, Geneva, 177pp.



    See Also:
       Toxicological Abbreviations
       Glyphosate (EHC 159, 1994)
       Glyphosate (ICSC)
       Glyphosate (Pesticide residues in food: 1986 evaluations Part II Toxicology)