GLYPHOSATE
EXPLANATION
Glyphosate has not been reviewed previously by the Joint Meeting.
CHEMICAL NAME N-(phosphonomethyl) glycine
SYNONYM Roundup(R)
STRUCTURAL FORMULA O O
" "
HOC - CH2 - NH - CH2 - P(OH)2
MOLECULAR FORMULA glyphosate: C3H8NO5P
isopropylamine salt: C6H17N2O5P
MOLECULAR WEIGHT glyphosate = 169.1
isopropylamine salt = 228.20
PHYSICAL STATE Non-volatile white solid
MELTING POINT 230°C (decomp.)
SOLUBILITY 12 g/l in water at 25°C.
Insoluble in common organic solvents.
IMPURITIES IN TECHNICAL MATERIAL:
Formulations: Roundup - aqueous concentrate with 360 g/l
glyphosate acid equivalents.
Application: By spraying as a 0.5 - 5% solution in
water or by wiping (rope-wick) as a 10 -
50% solution in water.
EVALUATION FOR ACCEPTABLE INTAKE
BIOLOGICAL DATA
Biochemical aspects
Absorption, distribution and excretion
Rats
After single oral doses of glyphosate (6.7 mg/kg b.w.) labelled
with 14C in 3 positions, absorption was incomplete (males,
approximately 15%; females, 35 - 40%). Excretion of absorbed material
was almost entirely in urine, although biliary excretion and
enterohepatic circulation did occur to a minor extent. Less than 1% of
the radiolabel was respired as 14CO2. The 48-hour clearance was 94
- 98% in males, 82 - 84% in females. The 120-hour clearance was 94% in
both males and females. Tissue retention was correspondingly low and
could be accounted for by incorporation of radiolabelled carbon
residues into muscle tissue (Colvin & Miller, 1973a).
The accumulation and depletion of 14C-glyphosate was
investigated by its daily administration at levels of 0, 1, 10, or
100 ppm for 14 days, followed by 10 days on a control ration.
Determinations of tissue residues were made throughout the treatment
and recovery periods. About 8.3 to 10.5% of the daily intake was
excreted in urine in both males and females. By 6 days, elimination
was approximately equal to intake. After cessation of treatment,
excretion declined rapidly; 4 days later a redistribution into the
excreta was seen, probably due to the mobilisation of previously
established body loads. Most tissues reached maximum residue levels at
10 days or less, with levels decreasing in the order: kidneys, spleen,
fat, liver, ovaries, heart, and muscle. The maximum level in the
kidneys at the high dose did not exceed 1 ppm on a fresh weight basis.
The residues declined markedly once treatment ceased. The maximum
level in the kidneys 10 days after withdrawal was 0.1 ppm, with
0.12 ppm in fat (Colvin & Miller, 1973b).
Rabbits
New Zealand white rabbits, administered single oral doses of
14C-glyphosate (6-8 mg/kg b.w.) cleared more than 40% of the
radioactivity in 5 days or less. More than 80% of the 14C-activity
appeared in the faeces, indicating poor oral absorption or extensive
biliary excretion. The remaining radioactivity after 5 days was mostly
recovered from the colon. Urinary excretion was 7 - 11% of the dose,
with less than 1% found in respired 14CO2. Tissue retention was
low (less than 0.1 ppm at 5 days), except for glyphosate labelled in
the glycine-2 position, which was metabolised to carbon fragments and
incorporated into tissues (Colvin & Miller, 1973c).
Monkeys
The percutaneous absorption of glyphosate from a commercial
formulation was studied in rhesus monkeys using 14C-labelled
material. Absorption was monitored by determining 14C-activity in
urine, after estimating the extent of urinary excretion following an
i.m. dose. Approximately 2% of the glyphosate in a single topical dose
penetrated the skin of monkeys in a 7-day period. Penetration was
slow, since only 0.4% of the applied dose appeared in the urine within
24 hours after treatment (Maibach, 1983).
Biotransformation
The metabolism of glyphosate in rats was studied after single
oral doses (6.7 mg/kg b.w.) labelled with 14C in 3 positions, or
after single i.p. injections of the same dose, or after 12 days
feeding with 14C-labelled glyphosate in the diet at 100 ppm.
Regardless of the route of administration, the major radioactive
component in urine and faeces was unchanged glyphosate. Minor peaks
were attributable to impurities in the 14C-glyphosate rather than to
metabolic conversion products (Moran et al., 1973).
Biochemical studies on metabolites
The metabolic fate of aminomethylphosphonic acid (AMP) was
studied, as this was the only major metabolite of glyphosate found in
biological systems. Male rats were given an oral dose of 14C-AMP
(6.7 mg/kg b.w.) and excreta were collected for 120 hours. AMP was
only moderately absorbed (approximately 20%). Excretion was almost
exclusively via the urine, with less than 0.1% of the dose respired as
14CO2. Tissue residues were less than 10 ppb (Colvin et al.,
1973).
Reaction of the secondary amine group of glyphosate with nitrite
could result in the production of N-nitrosophosphonomethyl glycine
(NPMG). Although this metabolite has never been detected in plant
residues, a study was performed to determine its metabolic fate in
rats. Animals received single oral doses of 13C/14C NPMG
(1 mg/kg). Urinary excretion accounted for 78 - 93% of the dose within
the first 24 hours, with a further 1 - 12% eliminated in faeces. The
urinary radioactivity was due to unchanged NPMG. In a second phase of
the study, animals were dosed orally with 13C/14C NPMG
(30 mg/kg/day) for 5 days to produce the maximal residues in organs
and tissues. Average excretion per day was 62% in urine and 31% in
faeces, with a total recovery of 93%. The 14C-content of tissues
after 5 days was low, ranging from 0.02 ppm in muscle to 0.90 ppm in
lung. Radioactivity in the urine, faeces, and tissues was in the form
of unchanged NPMG (Sutherland, 1978).
Toxicological studies
Special studies on mutagenicity
Glyphosate was consistently without mutagenic effect in a range
of short-term tests (see Table 1).
Special study on reproduction
Rats
Groups of 12 male and 24 female Sprague-Dawley rats were given
glyphosate (technical) in the diet at dose levels of 0, 3, 10, or
30 mg/kg b.w./day for 60 days. Administration was continued throughout
mating, gestation, and lactation for 2 successive litters (F1a and
F1b) and repeated for 3 generations.
Some deaths occurred in all treated groups, but there was no dose
relationship and probably no association with treatment. No evidence
of maternal or paternal toxicity was apparent. There were spurious
differences between control and treated animals in mating and
fertility indices, pregnancy rates, and pup survival. These effects
were not dose-related, and an association with treatment was unlikely.
Necropsy evaluation of all animals from the F0, F1b, and F2b
parents and F3b pups indicated no treatment-related effects. The
highest dose level of 30 mg/kg b.w./day was the no-observed-effect
level in this study (Schroeder, 1981).
Special studies on skin and eye irritation
Technical glyphosate (99% pure; 0.5 ml of 25%-strength solution)
and the isopropylamine salt of glyphosate (0.5 ml of undiluted
material) applied to the intact and abraded skin of rabbits for 24
hours produced no dermal irritation (Heenehan, 1979a; Branch, 1981a).
The same volume of the undiluted commercial formulation under the
same conditions as in the above experiment produced moderate to severe
skin irritation, which persisted in 1/6 animals for the duration of
the study (14 days). Other animals had recovered by 9 days
(Heenehan, 1979b).
Technical glyphosate (99% pure; 0.1 ml of 25%-strength solution)
instilled into the eye of rabbits produced conjunctival redness,
chemosis, and corneal opacity/ulceration. Washing the eyes with warm
water, 20 seconds after application, did not prevent the irritation.
All eyes were normal within 7 days (Heenehan, 1979c).
Under the same conditions as in the preceding experiment, the
same volume of the isopropylamine salt produced no irritation
(Branch, 1981b).
Table 1. Results of mutagenicity studies on glyphosate.
Test Test Concentration
system object of glyphosate Purity Results Reference
Ames test S. typhimurium 0.1 - 1000 98.4% negative1 Kier, 1978
strains TA98, µg/plate
TA100, TA1535,
& TA1537
Rec assay B. subtilis 20 - 2000 98.4% negative2 Shirasu
strain H17 µg/disc et al., 1978
(rec+) and
M45 (rec-)
Mutation E. coli 10 - 5000 98.4% negative1 Shirasu
assay strain WP2hcr µg/plate et al., 1978
Forward Chinese hamster 0 - 20 mg/ml 98.7% negative1 Li, 1983a
mutation ovary cells (w/o activation;
assay (HGPRT locus) 5 - 25 mg/ml (with
activation)
Unscheduled rat hepatocytes 0.0125 - 125 98.7% negative Williams,
DNA repair µg/ml 1983
assay
Table 1. (cont'd).
Test Test Concentration
system object of glyphosate Purity Results Reference
In vivo rat bone marrow 200 - 1000 98.7% negative Li, 1983b
cytogenetics mg/kg, i.p.
study
Dominant mice 200 - 2000 98.7% negative Rodwell,
lethal mg/kg, orally 1980a
assay
1 Both with and without metabolic activation.
2 Without metabolic activation.
Special study on skin sensitization
Undiluted glyphosate (0.2 ml) was applied dermally using the
closed patch technique to the shaved backs of Hartley guinea pigs
(5/sex). Application was for 6 hours/day, 3 days/week, for 3 weeks.
Two weeks after the final dose, additional (0.2 ml) doses were applied
to previously untreated areas. Dermal irritation was scored at 24 and
48 hours after the induction and challenge doses. Glyphosate did not
produce dermal sensitization in this model, but it did cause moderate
to severe irritation when applied repeatedly to the same site
(Auletta, 1983a).
This study was repeated using 0.2 ml doses of an undiluted
commercial formulation. A similar result was obtained to that using
the technical material, namely, no skin sensitization, but cumulative
skin irritation (Auletta, 1983b).
Special studies on teratogenicity
Rats
Groups of 25 female Charles River CD-1 rats were administered
glyphosate technical (97.7% pure) by gavage on days 6 - 19 of
gestation. Daily dose levels were 0, 300, 1000, and 3500 mg/kg b.w.
Control animals received only the vehicle (0.5% Methocel). Animals
were observed for clinical signs and mortality. Body weights were
recorded on gestation days 0, 6, 9, 12, 16, and 20. All surviving
animals were sacrificed on day 20, and the usual teratological
parameters were monitored. Approximately 50% of the fetuses were
examined for internal anomalies and 50% were examined for skeletal
anomalies.
There were no adverse effects of treatment at the mid- and
low-dose levels. Maternal toxicity was apparent at the high dose, with
soft stools, diarrhoea, red nasal discharge, reduced body-weight gain,
and 6 deaths by gestation day 17. The mean number of total
implantations, viable fetuses, and mean fetal body weights were
significantly reduced and early fetal resorptions were significantly
increased at this dose level.
There were no fetal malformations in the low- and mid-dose
groups. In the high-dose group there was an increase in the number of
fetuses with malformations, but the number of litters with
malformations was not increased. This increase in malformations was
attributable to dwarfism in one litter and bent tails in another. It
was unlikely that these were related to treatment. In addition, an
increase in the number of fetuses with unossified sternebrae was
apparent at the highest-dose level, which was probably related to the
severe maternal toxicity seen at this dose level. Accordingly,
glyphosate was not teratogenic in rats in this study (Rodwell, 1980b).
Rabbits
Groups of 16 female Dutch belted rabbits received technical
glyphosate by gavage in 0.5% Methocel on days 6 - 27 of gestation.
Dose levels were 0, 75, 175, and 350 mg/kg b.w./day. The control group
received the vehicle only. Animals were observed daily for clinical
signs and mortality. Body weights were determined on gestation days
0, 6, 12, 18, 24, and 28. All surviving females were sacrificed on
gestation day 28, and the usual teratological parameters were
examined. All fetuses were examined for both internal and skeletal
anomalies.
Maternal toxicity was apparent at the mid- and high-dose levels
as diarrhoea, soft stools, and nasal discharge (high-dose only). Two
mid-dose and 10 high-dose animals died during the study from unknown
causes. One control animal died from pneumonia. Two control, 1
mid-dose, and 1 high-dose animal aborted and were sacrificed. A slight
decrease in mean fetal body-weight was seen in all treated groups
compared to the control group, but the values were within historical
limits. There were no treatment-related effects on the number of
viable fetuses, early or late resorptions, or the fetal sex ratio.
There were no fetal anomalies which could be considered as
treatment-related, indicating a lack of teratogenicity in rabbits
(Rodwell, 1980c).
Acute toxicity
Glyphosate and its isopropylamine salt have extremely low acute
toxicity by oral, dermal and s.c. routes of administration. Toxicity
was greater by the i.p. route, however (see Table 2).
In animals which received lethal doses the most severe signs of
toxicity which preceded death were breathing difficulty, ataxia, and
occasional convulsive movements. At necropsy, discolouration was
observed in the lungs, liver, and kidneys of animals which had died.
Short-term studies
Mice
Groups of 15 male and 15 female Charles River CD-1 mice were fed
glyphosate technical in their diet at dose levels of 0, 0.5, 1.0, or
5.0% for 3 months. Animals were observed twice daily for clinical
signs and mortality. Body weights and food consumption were recorded
weekly. Complete gross necropsies were performed on all animals.
Histopathological examinations were performed on 10 animals of each
sex from the control and high-dose groups only.
Table 2. Results of acute toxicity studies on glyphosate (G), isopropylamine salt of
glyphosate (IPA-G), and undiluted Roundup(R) formulation (R).
Compound LD50
Species Route administered (mg/kg b.w.) Reference
Mouse oral G > 10,000 Monsanto, 1986
G 1,538 Monsanto, 1986
s.c. G in saline 6,250 (M) Monsanto, 1986
7,810 (F)
i.p. G in saline 545 (M) Monsanto, 1986
740 (F)
G 134 Monsanto, 1986
Rat oral G, R, & > 5,000 Heenehan, 1979d
IPA-G Branch, 1981c
dermal R > 17,600 Monsanto, 1986
inhalation R LC50 = 3.18 Velasquez, 1982
mg/l (4 hours)
s.c. G in saline 17,500 Monsanto, 1986
i.p. G in saline 281 (M) Monsanto, 1986
467 (F)
G 238 Monsanto, 1986
Rabbit oral G 3,800 Monsanto, 1986
dermal G, R, & > 5,000 Heenehan, 1979e
IPA-G Braun, 1979
Branch, 1981d
Goat oral G, R, & IPA-G > 3,500 Rowe et al., 1983
There were no clinical signs of toxicity and there was no
treatment-related mortality. Food consumption of males was increased,
but not of females. Body-weight gain was reduced in both males and
females at the high-dose level. Organ weights, gross necropsy
examinations, and histopathology were unremarkable. Thus, a dietary
level of 1.0% was without apparent effect (Tierney, 1979).
Rats
Groups of 15 male and 15 female Wistar-Imamichi rats were fed
glyphosate technical (98.4% pure) in their diets at dose levels of 0,
0.02, 0.2, 0.5, or 1.25% for 90 days. Animals were observed daily for
clinical signs and mortality. Body weights and food consumption were
recorded every 3 days. Haematological and urinary parameters were
determined at 90 days. Gross necropsy and histopathology were
performed on all animals.
There were no mortalities and no clinical signs of toxicity. Body
weights were slightly decreased in week 1 in both sexes, but not
thereafter. There were no biologically significant changes in
haematological, clinical chemical, or urinary parameters, or in organ
weights. Gross necropsy and histological findings were unremarkable.
Thus, a dietary level of 1.25% was without apparent effect (Tauchi,
1979).
A 4-week inhalation study was performed in rats with a one-third
dilution of a commercial glyphosate formulation. Three groups of 15
male and 15 female Sprague-Dawley rats were exposed to concentrations
of 0.05, 0.16, or 0.36 mg diluted commercial formulation per litre of
air, for 6 hours per day, 5 days per week, for 22 days. Toxicity was
confined to irritant effects on the nasal turbinates, trachea, and
lungs (Velasquez, 1983).
Rabbits
Three groups of 10 male and 10 female New Zealand rabbits were
treated dermally with glyphosate technical 5 days per week for
3 weeks. Dose levels were 100, 1000, or 5000 mg/kg b.w./day. The
application site was occluded for 6 hours after application and then
washed. The skin of 5 animals in each group was abraded before
application. Toxicity was apparent only as slight dermal irritation at
the 5000 mg/kg b.w./day dose level. There was no evidence of systemic
toxicity (Johnson, 1982).
The isopropylamine salt formulation of glyphosate was used in a
further 21-day dermal study in rabbits, using the same procedures as
in the preceding experiment. Six groups of 10 male New Zealand rabbits
were treated with 76 or 114 mg/kg b.w. undiluted formulation 5 days
per week for 21 days. Toxicity was apparent only as dermal changes,
which were more pronounced on abraded skin, but which in all cases had
healed by the end of a 28-day recovery period (Killeen, 1975).
Dogs
Groups of 6 male and 6 female beagle dogs were administered
technical glyphosate (96.1% pure) in gelatin capsules at dose levels
of 0, 20, 100, or 500 mg/kg b.w./day for approximately 1 year. All
animals were observed at least twice daily for clinical signs and
mortality. Body weights and food consumption were recorded weekly.
Ophthalmoscopic examination was performed before testing and at
termination. Haematologic and clinical chemical parameters were
evaluated pre-test and at months 3, 6, and 12. Urine was collected at
the same times for urinalysis. Gross necropsy and histopathological
examinations were performed on all animals.
There were no clinical signs of toxicity and no treatment-related
mortality. There were no remarkable ophthalmological findings and no
biologically-significant changes in haematological, clinical chemical,
or urinary parameters. There were no treatment-related changes in body
weight or organ weights and no remarkable findings at gross necropsy
or after histopathological examination. The no-observed-effect level
was considered to be 500 mg/kg b.w./day, the highest dose tested
(Reyna, 1985).
Long-term studies
Mice
In a combined chronic toxicity and carcinogenicity study, groups
of 50 male and 50 female Charles River CD-1 mice were fed technical
glyphosate in the diet for 24 months at levels of 0, 0.1, 0.5, or
3.0%. All animals were observed twice daily for mortality and clinical
signs of toxicity. Body weights and food consumption were determined
weekly for 14 weeks, then every 2 weeks for the remainder of the
study. Blood samples were taken from 10 animals/sex/group at 12 and 18
months and from 12 males/group and all surviving females at 24 months.
Gross necropsy was performed on all animals which died, were killed
in extremis, or were sacrificed at study termination.
There were no clinical signs of toxicity at any dose level.
Slight decreases in body-weight gain were seen in both high-dose
groups. Food consumption, feed efficiency, and water consumption were
unremarkable. There were no treatment-related haematological effects
or organ-weight changes. Hepatocyte hypertrophy, centrilobular
hepatocyte necrosis, and chronic interstitial nephritis were increased
in frequency in high-dose males. Proximal renal tubule epithelial
basophilia/hypertrophy was increased in frequency in treated females.
As the incidence of this lesion in the high-dose females was lower
than that in the control males and in the treated males, and because
the incidence in the high-dose females fell within the historical
control range, this effect was not considered to be related to
treatment. Hyperplasia of the urinary bladder was increased in
frequency in mid- and high-dose males, but not in treated females.
There were no statistically-significant increases in the
frequency of neoplastic lesions in treated groups. The incidence of
renal tubular adenomas in treated males was increased at the high-dose
level (control, 0/49, but 1/49 on re-examination; low-dose, 0/49;
mid-dose, 1/50; high-dose, 3/50). However, the incidence of this
tumour in historical controls was between 0 and 7.1% and a
treatment-related effect appears unlikely. The incidence of this
tumour was not increased in treated females. The no-effect level in
this study was determined to be 0.5% glyphosate, equal to
814 mg/kg b.w./day in males and 955 mg/kg b.w./day in females
(Hogan, 1983).
Rats
Groups of 50 male and 50 female Charles River Sprague-Dawley rats
were fed technical glyphosate in their diets at dose levels of 3, 10,
or 31 mg/kg b.w./day (males) and 3.4, 11, or 34 mg/kg b.w./day
(females) for approximately 26 months. Animals were observed twice
daily for clinical signs and mortality. Body weights and food
consumption were determined intitially, weekly to 14 weeks, and
biweekly thereafter. Blood and urine were collected from 10 animals/
sex/group at 4, 8, 12, 18, and 24 months. Full haematological and
clinical chemical determinations and urinalyses were performed on
those samples. All animals were subjected to gross pathological and
histopathological examinations.
There were no clinical signs of toxicity and no effects of
treatment on mortality. There were no treatment-related effects on
body weight at the end of the study, but there was a consistent
tendency for reduced body weights in treated males during most of the
growth period. Haematology, blood chemistry, and urinalysis were
unremarkable. There were no treatment-related effects on organ weights
and no remarkable findings at gross necropsy or after histopatho-
logical examination. There were no increases in tumours that were
treatment related. The incidence of interstitial cell tumours of
the testes was slightly high in the high-dose group (control, 0/15;
low-dose, 2/26; mid-dose, 1/16; high-dose, 4/26). However, this tumour
is common in aged rats and the incidence was not above historical
control levels. The no-observed-effect level exceeded 31 mg/kg
b.w./day in the diet (Lankas, 1981).
Observations in humans
The end-use dilution of commercial Roundup(R) formulations (1:9
Roundup(R): water) was tested for dermal irritation/sensitization in
humans using the repeated insult patch test. Aliquots of 0.9 ml were
applied to 50 human volunteers (14 males, 36 females) 3 times per week
for 5 weeks. The application site was occluded for 24 hours after
application. A challenge application was made 2 weeks after the last
application. No visible skin changes were observed in any subjects
(Shelanski, 1983).
The percutaneous absorption of 14C-labelled glyphosate from 3
formulations of glyphosate was measured in excised human abdominal
skin using an in-vitro technique. Glyphosate was found to be very
poorly absorbed under these conditions, with the epidermis acting as
the primary barrier (Franz, 1983).
COMMENTS
Glyphosate and its isopropylamine salt have extremely low oral
toxicity. Orally administered glyphosate is incompletely absorbed from
the gastrointestinal tract of rats, especially in males. It is
excreted unchanged in the urine, although there is evidence of biliary
excretion and enterohepatic circulation.
Glyphosate is not teratogenic in rats or rabbits at doses
producing maternal toxicity. It has no adverse effects on the
reproduction of rats, although doses were significantly lower than
those used in other studies. Glyphosate was without mutagenic activity
both in vitro and in vivo.
The chronic toxicity of glyphosate is low; the only significant
toxicity seen in a number of animal bioassays was mild hepatotoxicity
at high doses in mice. There is no evidence of carcinogenicity.
TOXICOLOGICAL EVALUATION
LEVEL CAUSING NO TOXICOLOGICAL EFFECT
Mouse: 0.5% in the diet, equal to 814 mg/kg b.w./day
Rat: 31 mg/kg b.w./day, administered in the diet.
Dog: 500 mg/kg b.w./day
ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR MAN
0 - 0.3 mg/kg b.w.
STUDIES WHICH WILL PROVIDE INFORMATION VALUABLE IN THE CONTINUED
EVALUATION OF THE COMPOUND
Further observations in man.
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1975 (Roundup(R) formulation) in male rabbits. Unpublished
report from Bio/Dynamics, Inc. (Project No. 1245/75),
E. Millstone, NJ, USA. Submitted to WHO by Monsanto Europe
S.A., Brussels, Belgium.
Lankas, G.R. A lifetime feeding study of glyphosate (Roundup(R)
1981 technical) in rats. Unpublished report from Bio/Dynamics,
Inc. (Project No. 410/77), E. Millstone, NJ, USA. Submitted
to WHO by Monsanto Europe S.A., Brussels, Belgium.
Li, A.P. CHO/HGPRT gene mutation assay with glyphosate. Unpublished
1983a report No. ML-83-155 from Monsanto Environmental Health
Laboratory, St. Louis, MO, USA. Submitted to WHO by
Monsanto Europe, S.A., Brussels, Belgium.
Li, A.P. In vivo bone marrow cytogenetics study of glyphosate in
1983b Sprague-Dawley rats. Unpublished report No. 83/236 from
Monsanto Environmental Health Laboratory, St. Louis, MO,
USA. Submitted to WHO by Monsanto Europe, S.A.,
Brussels, Belgium.
Maibach, M.I. Roundup(R) formulation. Elimination and dermal
1983 penetration in monkeys. Unpublished report No. 81/349 from
University of California School of Medicine. Submitted to
WHO by Monsanto Europe, S.A., Brussels, Belgium.
Moran, S.J., Colvin, L.B., & Ruepple, M.L. The metabolism of
1973 aminomethyl-phosphonic acid-14C in the laboratory rat.
Unpublished report No. 303 from Monsanto Environmental
Health Laboratory, St. Louis, MO, USA. Submitted to WHO by
Monsanto Europe, S.A., Brussels, Belgium.
Reyna, M.S. Twelve month study of glyphosate administered by gelatin
1985 capsule to beagle dogs. Unpublished report No. 83-137 from
Monsanto Environmental Health Laboratory, St. Louis, MO,
USA. Submitted to WHO by Monsanto Europe, S.A., Brussels,
Belgium.
Rodwell, D.E. Dominant lethal study in mice with technical glyphosate.
1980a Unpublished report No. 401-064 from International Research
and Development Corporation, Mattawan, MI, USA. Submitted to
WHO by Monsanto Europe, S.A., Brussels, Belgium.
Rodwell, D.E. Teratology study in rats with technical glyphosate.
1980b Unpublished report No. 79/016 from International Research
and Development Corporation, Mattawan, MI, USA. Submitted to
WHO by Monsanto Europe, S.A., Brussels, Belgium.
Rodwell, D.E. Teratology study in rabbit with technical glyphosate.
1980c Unpublished report No. 79/018 from International Research
and Development Corporation, Mattawan, MI, USA. Submitted to
WHO by Monsanto Europe, S.A., Brussels, Belgium.
Rowe, L.D., Lovering, S.L., Wilson, R.D., Martin, B.W., Peterson,
1983 H.O., Farr, F.M., & Moore, E.G. The acute oral toxicity of
glyphosate, Roundup(R) formulation, and glyphosate
isopropylamine salt in female goats. Unpublished report from
USDA Veterinary Toxicology and Entomology Research
Laboratory, College Station, TX, USA. Submitted to WHO by
Monsanto Europe, S.A., Brussels, Belgium.
Schroeder, R.E. Three generation reproduction study with glyphosate
1981 technical in albino rats. Unpublished report from
Bio/Dynamics, Inc. (Project No. 2063/77), E. Millstone, NJ,
USA. Submitted to WHO by Monsanto Europe S.A., Brussels,
Belgium.
Shelanski, M.V. Evaluation of potential hazards by dermal contact with
1973 Mon2134 (use concentrations). Repeated insult patch test.
Unpublished report from Shelanski Holding Co., PA, USA.
Submitted to WHO by Monsanto Europe, S.A., Brussels,
Belgium.
Shirasu, Y., Moriya, M. & Toshihiro, O. Microbial mutagenicity testing
1978 on CP67573 (glyphosate). Unpublished report No. 241/78 from
Institute of Environmental Toxicology. Submitted to WHO by
Monsanto Europe, S.A., Brussels, Belgium.
Sutherland, M.L. Metabolism of N-nitrosophosphonomethylglycine in the
1978 laboratory rat. Unpublished report No. MSL 0242 from
Monsanto Environmental Health Laboratory, St. Louis, MO,
USA. Submitted to WHO by Monsanto Europe, S.A., Brussels,
Belgium.
Tauchi, K. Sub-acute toxicity study of CP67573 (N-phosphonomethyl-
1979 glycine) to the rat in dietary administration for 90 days.
Unpublished report No. 79/112 from Institute for Animal
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Brussels, Belgium.
Tierney, W.J. Three month feeding study with technical glyphosate in
1979 mice. Unpublished report from Bio/Dynamics, Inc. (Project
No. 419/77), E. Millstone, NJ, USA. Submitted to WHO by
Monsanto Europe S.A., Brussels, Belgium.
Velasquez, D.J. Acute inhalation toxicity of Roundup(R) formulation to
1982 male and female Sprague-Dawley rats. Unpublished report
No. 81/201 from Monsanto Environmental Health Laboratory,
St. Louis, MO, USA. Submitted to WHO by Monsanto Europe,
S.A., Brussels, Belgium.
Velasquez, D.J. Four-week study of 33 1/3% use-dilution of Roundup(R)
1983 herbicide in water administered to male and female
Sprague-Dawley rats by inhalation. Unpublished report
No. 83/015 from Monsanto Environmental Health Laboratory,
St. Louis, MO, USA. Submitted to WHO by Monsanto Europe,
S.A., Brussels, Belgium.
Williams, G.M. The hepatocyte primary culture/DNA repair test on
1983 compound JJN-1020 using rat hepatocytes in culture.
Unpublished report No. AH-83-181 from Naylor Dana Institute
for Disease Prevention, Valhalla, NY, USA. Submitted to WHO
by Monsanto Europe, S.A., Brussels, Belgium.
See Also:
Toxicological Abbreviations
Glyphosate (EHC 159, 1994)
Glyphosate (ICSC)