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Extension Toxicology Network

A Pesticide Information Project of Cooperative Extension Offices of Cornell University, Michigan State University, Oregon State University, and University of California at Davis. Major support and funding was provided by the USDA/Extension Service/National Agricultural Pesticide Impact Assessment Program.



Lactofen is the active ingredient in Cobra herbicide and may also be called PPG-844 (1, 2).


Lactofen is a Restricted Use Pesticide in EPA toxicity class I. Although it is slightly toxic via all routes of exposure (i.e., oral, dermal and inhalation; see below) in test animals, it has the capacity to cause severe eye damage as well as skin corrosion (3, 4). Products containing Lactofen must therefore bear the signal word DANGER (1).


Lactofen is a member of the diphenyl ether chemical family (2). It is available in the technical solid form or as an emulsifiable concentrate (1, 2). It is applied as a foliar spray on target weeds(3). It is commonly used to control broadleaf weeds in soybeans, cereal crops, potatoes and peanuts (2, 3). It may commonly be combined with oil or fertilizer adjuvants and/or surfactants (3). Formulations may contain solvents such as xylenes and cumene (4).

Toxicological, environmental chemistry and fate data presented here refer to the technical compound unless otherwise noted.



Lactofen is slightly to practically non-toxic by ingestion; reported oral LD50s for it are 2,400 mg/kg (4) to greater than 5,000 mg/kg in rats (1, 2). Other reported oral LD50s for it are 5,960 mg/kg for the technical compound and 2,533 mg/kg for the formulated herbicide Cobra, both in rats (3).

Lactofen is slightly to practically non-toxic by inhalation as well; reported 4-hour inhalation LC50s in rats are >3.6 mg/L (3) for the technical compound and 6.65 mg/L (3, 4) for the formulation (Cobra) in rats.

Via the dermal route, both the technical compound and the formulated compound (Cobra) are slightly to practically non-toxic with reported LC50s of >2,000 mg/kg in rabbits(1, 2, 3). No skin sensitization occurred in the guinea pig, although severe eye irritation was noted in the rabbit (3).

Lactofen can cause severe eye and skin irritation. Effects of exposure are reddening and swelling of the skin, and possibly corrosive burns (4). It is a severe eye irritant, and can cause permanent damage to eyes with sufficient exposure (4).


In a 90-day feeding study on rats, no effects were observed at doses of 10 mg/kg/day, and the lowest dose at which effects were observed was 50 mg/kg/day (3). Effects observed were increased liver and kidney pigmentation, decreased red blood cell counts as well as decreases in blood hemoglobin levels (3, 5). In another study on rats, doses of 25 mg/kg/day produced no observable effects over 24 months (3, 5). In this study, kidney and liver pigmentation were noticeable at 50 mg/kg/day (3, 5). Other effects, possibly related to tumor formation, were also observed in rats (see the section on Carcinogenic Effects).

In an 18-month dietary study on mice, increased liver weights and liver cell size (cytomegally) were observed at doses of 1.5 mg/kg/day (3, 5). In a 12-month dietary study on dogs, no effects were observed at 5 mg/kg/day (3, 5). Doses of 25 mg/kg/day and higher over the 12-month period produced kidney dysfunction as well as increases in red blood cell count, hemoglobin, cholesterol and other blood parameters (3, 5).

Reproductive Effects

Reduced mean pup weight as well as increased pup heart and liver weights were observed in rats at dietary doses of 25 mg/kg/day over a two-generational study (3, 4, 5). In another study of rats, possibly of shorter duration, no effects were observed at 50 mg/kg/day, but increased post-implantation loss and reduced pup body weight were observed at a higher dose of 150 mg/kg/day in the same study (3, 5).

Reduced maternal food consumption was observed at dietary doses of 20 mg/kg/day in a study on rabbits of unspecified duration (3). It is unlikely that lactofen would cause reproductive effects in humans under normal conditions.

Teratogenic Effects

Fetal bent ribs were observed at doses of 150 mg/kg/day in the second rat study referenced above (5). No fetotoxic or teratogenic effects were observed at dietary doses of 20 mg/kg/day and higher in a study on rabbits of unspecified duration (3).

It is unlikely that lactofen would have teratogenic effects in humans under normal conditions.

Mutagenic Effects

Results of the Ames mutagenicity assay for lactofen were inconclusive in two trials; one trial was positive for mutagenicity and one was negative (3). Tests of lactofen's capacity to induce chromosomal aberrations, unscheduled DNA synthesis and inhibit DNA repair were all negative (3). Lactofen shows little if any mutagenic or genotoxic activity.

Carcinogenic Effects

An increase in the combined incidence of liver adenoma and carcinoma was observed in mice at dietary doses of 37.5 mg/kg/day over an 18-month period (5). Increases in liver neoplastic nodules and foci of cellular alteration (possible precursors to tumors) were noted in rats at dietary doses of 50 mg/kg/day over two years (5).

This evidence indicates that at very high doses, lactofen may show some carcinogenic activity. It is classified by EPA as a B2 (probable) human carcinogen (6).

Organ Toxicity

Based on the reported results of animal tests cited above, organ systems potentially affected by exposure to lactofen include the liver and kidneys.

Fate in Humans & Animals

No information is available regarding disposition of the compound in mammalian systems.


Effects on Birds

Lactofen is practically non-toxic to studied bird species . The reported oral LD50 value is greater than 2,510 mg/kg for the bobwhite quail (2, 3). Reported eight-day dietary LC50s for technical lactofen are >5,620 ppm in the mallard and duck (3). The formulated product (Cobra), having a lesser proportion of active ingredient, is probably less toxic to birds.

Effects on Aquatic Organisms

Lactofen's toxicity to fish and other aquatic organisms varies greatly; the formulated product is probably more toxic than the technical product. Reported 96-hour LC50s for the technical product are higher than the reported water solubility (3), which indicates that toxic effects to fish and other aquatic species may be unlikely due to its very low water solubility.

Reported 96-hour LC50s for the formulated product (Cobra), however, are 0.49 mg/L and greater than 0.85 mg/L for bluegill sunfish and rainbow trout respectively (6), indicating high toxicity. This high toxicity may be in large part due to the increased water solubility and bioavailability of the compound in the emulsified form.

Reported 48-hour LC50s for Daphnia, an aquatic invertebrate species important as a food source for many aquatic species and indicator species, are 2 mg/L for the technical product and 5.1 mg/L for Cobra (3), indicating high toxicity for both forms.

Due to its low water solubility (hence high lipid solubility) lactofen may have the potential to bioconcentrate. The reported whole body fish bioconcentration factor (concentration in the fish on a whole-body basis versus the environmental concentration) is 380X after 30 days exposure (6, 8). Elimination of the compound by the fish (depuration) was almost complete within 14 days, and 58% was eliminated within the first day.

Effects on Other Animals (Nontarget species)

An LD50 of greater than 160 ug/bee is reported for the technical compound in honeybees (6), indicating low toxicity for this species. No data were available regarding the toxicity of lactofen to earthworms or other non- target species.


Breakdown of Chemical in Soil and Groundwater

Lactofen is of low persistence in most soil types (3, 7). Reported field half-lives range from 1 to 7 days (3, 7, 8). It is rapidly degraded, mainly by microbial activity rather than hydrolysis (3), although hydrolysis is more likely at pH 9 and above, conditions which are unlikely in soil environments (3, 8). Aerobic conditions speed the rate of microbial breakdown of lactofen (3, 6, 8). Photolysis (breakdown from the energy of sunlight) and volatilization loss are thought to be minimal (3).

Lactofen is tightly bound to most soils (3, 5), and is therefore likely to be immobile in most cases. Its primary degradate, acifluorfen, is, however, mobile to highly mobile in soils, depending on soil type and organic matter content (3), and may also be moderately persistent (2). Acifluorfen is generally not more toxic than lactofen, and is less toxic to aquatic species than lactofen (2).

Breakdown of Chemical in Surface Water

Lactofen has a very low water solubility and is tightly bound to soil, so it is therefore not expected to be prevalent in surface waters. One possible source of infiltration into surface waters would be surface runoff. In this event, the compound would most probably remain bound to the solid particle and settle to the bottom.

Lactofen is stable at pH 5-7 but will readily undergo hydrolysis at pH 9 and above (3, 6). Since surface waters only rarely reach this level of alkalinity, this process will not contribute greatly to any degradation of lactofen. Reported half-lives for lactofen in water are 5-10 days (8).

Breakdown of Chemical in Vegetation

Lactofen is readily absorbed through the foliage, but translocation is limited in most species of broadleaf plants (3). It is readily metabolized, with detectable residues absent after 24 hours (3). Biosynthesis of chlorophyll and heme is disrupted in susceptible plants, and there is evidence of membrane damage due to lipid peroxidation (3) which may contribute to observed yellowing, cell death and foliar bronzing. Data regarding the plant metabolites of lactofen were unavailable.


Technical lactofen is a white crystalline solid (3), although it may appear brown or tan in formulation (1, 2).

Exposure Guidelines:

ADI: 0.0015 mg/kg/day (6)
HA: Not Available
RfD: 0.002 mg/kg/day (5)
PEL/TLV: Not Available

Physical Properties:

Chemical Name: ethyl O{5-(2-chloro-a,a,a-trifluoro-p-toluoxy)-2-nitrobenzoyl}-DL-lactate
CAS: 77501-63-4
Molecular Weight: 461.78 (2)
Water solubility: 0.1 mg/L @ 20 degrees C (2, 3)
Solubility in other solvents: isopropanol s., acetone s., xylene s. (3)
Melting Point: 43.9 - 45.5 degrees C (3)
Vapor Pressure: 1.1 x 10 to the minus 3 mPa @ 25 degrees C (3)
Partition Coefficient (octanol/water): 100,000 (9)
Adsorption Coefficient: Koc = 10,000 (7)


Valent USA Corporation
P. O. Box 8025
Walnut Creek, CA 94596-8025
Phone: 510-256-2700
Emergency: 800-892-0099

Review by Basic Manufacturer:

Comments solicited: June, 1995
Comments received: July, 1995


  1. Meister, R. T. (ed.) 1992. Farm Chemicals Handbook '92, Meister Publishing Co. Willoughby, OH.
  2. Royal Society of Chemistry. 1991 (as updated). The Agrochemicals Handbook. Royal Society of Chemistry Information Services. Cambridge, UK.
  3. Weed Science Society of America. 1994. Herbicide Handbook, Seventh Edition. Weed Science Society of America. Champaign, IL.
  4. Valent USA. 1993. Material Safety Data Sheet for Valent Cobra Herbicide. Valent USA Corporation. Walnut Creek, CA.
  5. US Environmental Protection Agency. 1995. File: Lactofen, Integrated Risk Information System (IRIS). National Library of Medicine "Toxline" Database, 4/95.
  6. US Environmental Protection Agency. 1987. Fact Sheet Number 128: Lactofen. Washington, DC.
  7. Wauchope, R.D., Buttler, T.M., Hornsby A.G., Augustijn-Beckers, P.W.M. and Burt, J.P. 1992. SCS/ARS/CES Pesticide Properties Database for Environmental Decisionmaking. Reviews of Environmental Contamination and Toxicology, Vol. 123.
  8. US Environmental Protection Agency. 1993. Environmental Fate and Effects Division. Pesticide Environmental Fate One Line Summary: Lactofen. Washington, DC.
  9. Bruce, E., Product Manager, Personal Communication. 1995. Valent USA Corporation. Walnut Creek, CA.