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WORLD HEALTH ORGANIZATION

WHO/PCS/DS/96.82

ORGANISATION MONDIALE DE LA SANTE

Original: ENGLISH

FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS

Distr.: LIMITED

ORGANISATION DES NATIONS UNIES POUR L’ALIMENTATION ET L’AGRICULTURE

Date of issue: July 1996

WHO/FAO DATA SHEETS ON PESTICIDES

No. 82

ATRAZINE

1.0 GENERAL INFORMATION
1.1 Common Name:
1.1.1 Identity:
1.1.2 Synonyms and trade names:
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 mainly controlled:
1.4.3 Use pattern:
1.4.4 Unintended effects:
1.5 Public Health Programmes:
1.6 Household Use: No Recommended Uses.
2.0 TOXICOLOGY AND RISKS
2.1 Toxicology - Mammals
2.1.1 Absorption route:
2.1.2 Toxic effects:
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 Long-term toxicity and carcinogenicity
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 population:
2.2.5 Observations on volunteers:
2.2.6 Reported mishaps:
2.3 Toxicity - 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 Transport And Storage
3.3 Handling
3.4 Disposal And/Or Decontamination Of Containers
3.5 Selection, Training And Medical Supervision Of Workers
3.6 Labelling
3.7 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:
4.2 Entry Of Persons Into Treatment Area
4.3 Disposal Of Spillage
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:

Triazine

1.0 GENERAL INFORMATION

1.1 Common Name:

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

1.1.1 Identity:

IUPAC name:

6-chloro-N-ethyl-N’-isopropyl-1,3,5-triazine-2,4-diamine

CAS name:

6-chloro-N-ethyl-N’-(1-methylethyl)-1,3,5-triazine-2,4-diamine

CAS Registry number:

1912-24-9

RTECS number:

XY5600000

Molecular formula:

C8H14ClN5

Relative molecular mass:

215.7

Structural formula:

Structural Formula

1.1.2 Synonyms and trade names:

A 361; AAtrexR; AAtrex-nine-o; Actinite PK; Aktikon; Aktikon PK; Aktinit A; Aktinit PK; Argezin; Atrazinex; AtranexR; Atrasine; Atrataf; Atrazin; AtratolR; AtredR; Candex; Cekuzina-T; Chromozin; CrisazineR; Cyazin; Farmco; Atrazine; Fenatrol; G30027; GesaprimR; GriffexR; Hungazin; Hungazin PK; Oleogesaprim; Inakor; Primatol A; Pitezin; Primase; Vectal SCR; Weedex A; Wonuk; ZeazinR; Zeazine.

1.2 Synopsis:

Atrazine is a broad spectrum triazine herbicide; used at low levels it is selective while at high levels it acts as a total herbicide and in both cases has residual activity of up to one year. Atrazine is of slight acute toxicity to mammals.

1.3 Selected Properties

1.3.1 Physical characteristics:

Atrazine is a colourless, crystalline solid with a m.p. 175-177 ºC, Density 1.187 g/cm3 at 20 ºC.

1.3.2 Solubility:

0.030 g/litre in water at 20 ºC

0.360 g/litre in N-pentane at 27 ºC

52 g/litre in chloroform at 27 ºC

183 g/litre in dimethyl sulfoxide at 27 ºC

27 g/litre in ethyl acetate at 27 ºC

12 g/litre in diethyl ether at 27 ºC

15 g/litre in methanol at 25 ºC

1.3.3 Stability:

Stable to acid, alkali and neutral media; slightly sensitive to natural light and extreme temperatures. Good shelf-life and residual activity.

1.3.4 Vapour pressure:

0.039 mPa at 25 ºC

*Kow log P=2.5 at 25 ºC

*pKa = 1.7

1.4 AGRICULTURE, HORTICULTURE AND FORESTRY

1.4.1 Common formulations:

Granules, water dispersible granules, liquid, suspension concentrate, wettable powder; also in combination with many other herbicides. Compatible with various insecticides and fungicides.

1.4.2 Pests mainly controlled:

Atrazine is a pre- and post-emergence herbicide which effectively stops photosynthesis, thereby killing the plant. Gives selective control of grasses or annual weeds in corn, sorghum, sugar cane or pineapples; in forestry cultivation; and selective control of pond-weeds, especially submerged aquatic plants. High application rates give non-selective control in non-crop areas.

1.4.3 Use pattern:

Pre-emergence of the desirable crop is the preferred method of application, but pre-plant or post emergence, applied when weed seedlings are less than 4 cm high are effective. Shallow incorporation into soil or moisture increase activity.

1.4.4 Unintended effects:

Toxic to some algae. Failure to observe correct application intervals may cause toxicity to rotational crops, due to residual soil activity. Vegetable crops, cereal grains, soybeans, peanuts and potatoes are very sensitive to atrazine.

1.5 Public Health Programmes:

No recommended uses.

1.6 Household Use: No Recommended Uses.

2.0 TOXICOLOGY AND RISKS

2.1 Toxicology - Mammals

2.1.1 Absorption route:

Readily absorbed from the gastrointestinal tract and may be absorbed from the lungs or through intact skin.

2.1.2 Toxic effects:

Atrazine has some neuro-muscular toxicity at high doses, causing motor incoordination, limb paralysis, respiratory distress and hypothermia in laboratory animals.

2.1.3 Excretion products:

Following oral administration of 0.5 or 5.5 mg/kg b.w. 14C-ring labelled atrazine to rats, numerous urinary metabolites were detected. The major metabolites were the mono-or di-N-dealkylation products. At the lower dose, 72 hour recoveries of radioactivity were 66, 20 and  0.1% for urine, faeces and expired air, respectively. At 72 hours the carcass residue was 16% of the dose, and at eight days 14C-residues were still detectable in the liver, lung, heart, brain and kidney. Similar metabolite profiles have been observed in pigs, and from in vitro experiments with rat liver, the latter experiments also demonstrating the formation of glutathione conjugates as minor metabolites. (Section 2.1.7).

2.1.4 Toxicity, single dose:

Oral LD50

Rat

1869-3080 mg/kg b.w.

Mouse

1750 mg/kg b.w. - 3992 mg/kg b.w.

Rabbit

750 mg/kg b.w.

Dermal LD50

Rabbit

7,500 mg/kg b.w.

Rat

>3,100 mg/kg b.w.

Inhalation LD50 (4hr)

Rat

>710 mg/m3

 

>5800 mg/m3

Toxicity following oral or intraperitoneal administration to rat was characterized by initial excitation, followed by depression with reduced respiratory rate, motor incoordination, clonic and occasionally tonic spasms, and hypothermia. Rats that died within six hours of an oral dose of 3000 mg/kg b.w. showed lung oedema with extensive haemorrhagic foci, cardiac dilation and macroscopic haemorrhages of liver and spleen. In addition, dystrophic changes in kidney tubules were observed in rats that died during the 2nd day.

Dermal irritancy: 38 mg/rabbit caused mild irritation.

Eye irritancy: 6.3 mg caused severe irritation to rabbit eyes.

2.1.5 Toxicity, repeated dose:

Oral administration of 120 mg/kg b.w./day to rats for six months, resulted in 40% mortality. Respiratory distress and paralysis of the hind limbs were noted in these rats.

Intraperitoneal: Technical atrazine (97.2% pure) in corn oil was lethal to male mice following administration at dose levels >600 mg/kg b.w./day for up to five days.

2.1.6 Dietary studies:

Short-term: Six months dietary administration of 5 or 25 mg/kg b.w. (diet) to rats caused growth retardation (partly due to reduced food intake) and altered thiamine and riboflavine metabolism. On histopathological examination no significant lesions were observed.

2.1.7 Long-term toxicity and carcinogenicity

Atrozine has been subjected to exctensive long-term toxicity testing on rats, mice and dogs. Significant toxicity was observed in dogs after long-term oral administration at doses of 5 mg/kg b.w./day and above. In rats and mice, reduced food intake, decreased body weight, muscle and retinal degeneration, hepatotoxicity and haematological disturbances were observed. An increase in mammary tumours (mainly benign) was observed in male rats but not in mice following long-term oral administration. In the females, the incidence of uterine adenocarcinomas and of tumours of the haematopoietic system were increased. However, taking into account technical difficulties (abnormally high background incidence of mammary tumours in untreated animals, exceeded maximum tolerated dose) these findings were not considered as convincing evidence of carcinogenicity. IARC classified atrazine in "groupe 2B" "possibly human carcinogen" with "limited evidence" in experimental animals.

2.1.8 Teratogenicity:

Doses of 10, 70 or 700 mg/kg b.w./day of technical atrazine were administered by gavage to rats on gestation days 6 to 15 and doses of 1, 5 or 75 mg/kg b.w./day were orally administered (by gavage) to rabbits on gestation days 7 to 19. Incomplete skeletal ossification increased with the intermediate dose (70 mg/kg b.w./day) and above; other effects on the rat foetus were observed only at maternally toxic doses, in the form decreased foetal weight at the high dose level (700 mg/kg b.w./day). In rabbits, increased absorption rate, decreased litter size, lowered foetal weight and a higher incidence of incomplete ossification were observed at the high dose level (75 mg/kg b.w./day) which was also maternally toxic. It was concluded that atrazine is embryotoxic and embryolethal but not teratogenic in rats and rabbits when administered at maternally toxic doses.

2.1.9 Mutagenicity:

The genotoxic potential of atrazine has been tested in a large number (more than 90) of assays evaluating various end points both in vitro and in vivo. Atrazine did not induce mutations in several bacterial tests. Inconsistent positive results were observed in Drosophila melanogaster. In cultured rodent and human cells atrazine did not induce chromosomal aberrations, sister chromatid exchange or unscheduled DNA synthesis. The overall evaluation of the results of these tests has concluded to the lack of mutagenicity.

2.1.10 Reproduction:

No published information available.

2.2 Toxicology - Man

2.2.1 Absorption route:

Atrazine has the potential to be absorbed from the gastrointestinal tract, by inhalation, and through the intact skin of man. No published information is available on the extent of absorption.

2.2.2 Dangerous doses:

Single: No published information available.

Repeated: No published information available.

2.2.3 Observations on occupationally exposed workers:

In the United States of America between 1966 and June 1981, 65 incidents of human overexposure to atrazine during industrial, agricultural or unspecified occupations were recorded. Ten of these incidents involved exposure to atrazine alone. One death is reported following extensive dermal exposure from spillage. No details are available, but the subject did not seek medical attention. Ocular and dermal irritation, chest pains, a feeling of tightness in the chest, dizziness and nausea have been reported following dermal, oral or inhalation exposures.

2.2.4 Observations on exposure of the general population:

Nausea and dizziness were reported following exposure to contaminated well-water or run-off from adjacent fields sprayed with atrazine.

2.2.5 Observations on volunteers:

No published information available.

2.2.6 Reported mishaps:

Two incidents are reported from the United States of America between 1966 - 1981 involving children accidentally ingesting atrazine. In both cases the subjects remained asymptomatic. Neither report quantitates the amount of atrazine ingested.

2.3 Toxicity - Non-Mammalian Species

2.3.1 Fish:

LC50 96 hour

Rainbow trout

4.5- 11.0 mg/litre

 

Carp

76 - >100 mg/litre

 

Bluegill

16 mg/litre

 

Coho salmon

15 mg/litre

 

Catfish

7.6 mg/litre

 

Guppy

4.3 mg/litre

During a 2-18 month exposure study, bluegills, fathead minnows and brook trout showed no evidence of bio-concentration of atrazine.

2.3.2 Birds:

Acute LD50

940 mg/kg b.w. quail - >10,000 mg/kg b.w. Peking duck

LC50

 

(5 days dietary exposure)

 

Bobwhite quail

5000 mg/kg diet

Japanese quail

> 5000 mg/kg diet

Ring-necked pheasant

> 5000 mg/kg diet

Mallard duck

> 5000 mg/kg diet

Oral administration of 100, 200 or 400 mg atrazine in capsules, once a week for 15 weeks, had no effect on weight gain, number of eggs laid, shell thickness or chick survivability in pheasants, even though lower egg weights occurred at 200 and 400 mg doses.

2.3.3 Other species:

In Bufo americanus, B. fowleri, Rana catesbeiana and R. pipiens a medial lethal concentration of atrazine was established at 0.41 - 48 mg/litre for continuous exposure from fertilization until four days post-hatching. Treatment of ponds with 0.02 or 0-5 mg/litre concentrations of atrazine depressed growth in some phytoplankton species. The algal biomass was maintained through colonization by resistant species. Laboratory investigation determined that concentrations as low as 0.001 - 0.005 mg/litre could alter the phytoplankton colonization pattern.

Daphnia magna

EC50 (48h)

6.1 mg/litre

 

EC50 (21 days)

>0.12 mg/litre

Bees

LD50 (oral)

> 97 µg/bee

 

LD50 (contact)

>100 µg/bee

Earthworm

LC50 (14 days)

78 mg/kg of soil

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".]

Liquid formulations greater than 10%, and solid formulations greater than 40%: Category 4.

All other liquid and solid formulations - Category 5.

3.2 Transport And Storage

Formulations in category 4: Should be transported and stored in clearly labelled, rigid and leak-proof containers. Containers should be kept under lock and key, secure from access by children and other unauthorized persons and well away from food and drink.

Formulations in category 5: Should be transported and stored in clearly labelled, leak-proof containers, out of reach of children and away from food and drink.

3.3 Handling

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

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

3.4 Disposal And/Or Decontamination Of Containers

Low water solubility and the stability of atrazine to acid or alkali make decontamination of the container impractical. The empty container should be burned or crushed and buried below topsoil, ensuring that water sources are not contaminated.

3.5 Selection, Training And Medical Supervision Of Workers

Formulations in category 4: Pre-employment medical examination of workers is desirable. Special account should be taken of workers’ ability to comprehend and follow instructions. Training of workers in techniques to avoid contact is desirable.

3.6 Labelling

Formulations in category 4 - Minimum cautionary statement: Atrazine is a triazine herbicide and should no be used by people under medical advice not to work with such compounds. Atrazine is a mild skin irritant and a severe eye irritant. Avoid all mouth, skin and eye contact or inhalation of spray, dust or mists. Wash splashes from skin and eyes immediately. Wash hands before eating or smoking after handling the pesticide; change clothing and shower or bathe, immediately after work. When handling concentrates wear gloves, goggles, and clean protective clothing. Ensure that food or animal feedstuffs are removed from treatment area to avoid contamination.

Formulations in category 5 - Minimum cautionary statement: This formulation contains atrazine. Avoid all mouth and skin contact, or inhalation of spray mist or dust. Wash hands after use.

3.7 Residues In Food

Maximum residue limits for atrazine have not yet been considered by the FAO/WHO Joint Meeting on Pesticide Residues. Maximum residue limits have been recommended in several countries.

4.0 PREVENTION OF POISONING IN
MAN AND EMERGENCY AID

4.1 Precautions In Use

4.1.1 General:

Atrazine is a triazine herbicide of low acute mammalian toxicity. High doses cause neuro-muscular effects in laboratory animals. Atrazine is a mild skin irritant and severe eye irritant and may cause an allergic reaction.

4.1.2 Manufacture and formulation - TLV:

5 mg/m3. Closed systems and forced ventilation are required to reduce worker-exposure to atrazine.

4.1.3 Mixers and applicators:

When opening the container and when mixing, care should be taken to avoid contact with the skin, mouth and eyes. Protective overalls, goggles, and gloves should be worn. Mixing, if not mechanical, should always be carried out with a paddle of appropriate length. Splashes should be washed immediately from the skin or eyes with large quantities of water. Before eating, drinking or smoking, hands and exposed skin should be washed. Clothing should be washed at the end of a working day.

4.2 Entry Of Persons Into Treatment Area

Unprotected persons should be kept out of treated areas until the residues are dry.

4.3 Disposal Of Spillage

Do not allow liquid or solid formulations to contact the skin or eyes. Contain liquid spills with an adsorbent material. Bury this material, or small spills of solid formulations in a deep pit, unless local regulations require different disposal practice, ensuring that water resources will not be contaminated. Wash the spillage site with large volumes of water and detergent. Do not allow wash waters to run off and reach ditches, streams or sewages.

4.4 Emergency Aid

4.4.1 Early symptoms of poisoning:

Atrazine is irritating to skin, eyes and upper respiratory tract. Acute systemic toxicity is unlikely unless very large amounts have been ingested. No data has been published on human systemic toxicity, and only at high doses have other mammalian species suffered neurotoxic and respiratory effects.

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

The person should stop work immediately, remove contaminated clothing and wash the affected skin area with copious amounts of water. If swallowed and the person is conscious, vomiting should be induced. In the event of collapse, artificial respiration should be administered.

5.0 FOR MEDICAL AND LABORATORY PERSONNEL

5.1 Medical Diagnosis And Treatment In Cases Of Poisoning

5.1.1 General information:

Atrazine is a triazine herbicide with low acute mammalian toxicity. It may be absorbed from the gastrointestinal tract, through the intact skin, and by inhalation.

5.1.2 Symptoms and signs:

Irritation of skin and eyes is the most frequent symptom observed.

5.1.3 Laboratory:

No published information available. Urinary determination of atrazine and its metabolites would indicate the degree of exposure.

5.1.4 Treatment:

Treatment is symptomatic. If the pesticide has been ingested in large quantities, unless the patient is vomiting, gastric lavage should be performed. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of water.

5.1.5 Prognosis:

The low acute toxicity of atrazine and mild nature of symptoms reported suggest that the prognosis for recovery from atrazine exposure is good.

5.1.6 References to previously reported cases:

Pesticide Incident Monitoring System (1981) Report No. 465. Office of Pesticide Programs, U.S. Environmental Protection Agency.

In addition, there is a description of the effects of this herbicide on humans: Schlicher JE and Beat VB (1972), Dermatitis resulting from herbicide use - a case study. J Iowa Med Soc, 62:419-20.

5.2 Surveillance Tests

No published information available.

5.3 Laboratory Methods

5.3.1 Detection and assay of compound:

Beilstein P, Cook AM, Hutter R (1981), J Agric Food Chem, 29(6): 1132-1135.

5.3.2 Other tests in case of poisoning:

No published information available.

REFERENCES

IARC (1991), Atrazine. In: Occupational Exposures in Insecticide Application, and some Pesticides. Lyon, International Agency for Research on Cancer, pp.441-466. (IARC Monograph on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol.53).

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.



    See Also:
       Toxicological Abbreviations
       Atrazine (HSG 47, 1990)
       Atrazine (ICSC)
       Atrazine  (IARC Summary & Evaluation, Volume 53, 1991)
       Atrazine  (IARC Summary & Evaluation, Volume 73, 1999)