METHAMIDOPHOS
EXPLANATION
First draft prepared by Dr E.M. den Tonkelaar,
National Institute of Public Health and Environmental Protection,
Bilthoven, The Netherlands
Methamidophos toxicity was evaluated by the JMPR in 1976, 1982
and 1985 (Annex 1, FAO/WHO 1977ab, 1983ab and 1986ac). In 1985 the
Meeting allocated an ADI of 0-0.0006 mg/kg bw, based on a complete
data package which replaced invalid IBT (Industrial Biotest) data.
Because methamidophos is a metabolite of acephate, for which an ADI
had been established based on a study in humans, it was decided to re-
evaluate methamidophos. This study was considered at the present
Meeting as well as new data on in vitro cholinesterase inhibition
and on delayed neuropathy.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
BIOLOGICAL DATA
Biochemical aspects
Effect on cholinesterase activity
The cholinesterase inhibition of methamidophos, acephate and
paraoxon (a known strong anticholinesterase) were determined on human
erythrocytes and on brain samples of rats, mice and rainbow trout in
an in vitro experiment. In all cases, except trout brain
cholinesterase, acephate and methamidophos were found to be six and
three orders of magnitude weaker than paraoxon, respectively (see
Table 1) (Hussain et al., 1985).
Table 1. Concentrations of acephate, methamidophos and paraoxon required
to inhibit 50% of the activity (I50) of cholinesterases from human
erythrocyte, rat, mouse and trout brain in vitro.
Chemical Human Rat brain Mouse brain Trout brain
erythrocyte
Acephate
(x 10-2M) 1.9 ± 0.1 0.7 ± 0.008 6.0 ± 2.0 2.8 ± 0.3
Methamidophos
(x 10-5M) 2.3 ± 0.3 2.0 ± 0.2 2.0 ± 0.2 5.6 ± 0.9
Paraoxon
(x 10-8M) 3.3 ± 0.5 2.3 ± 0.3 5.0 ± 0.8 2200 ± 100
Sprague-Dawley rats (5/sex/group) received single topical
applications of analytical grade methamidophos (purity 99.1%) and
methamidophos technical (purity 74.7%) at dose levels of 0, 1.0, 2.5,
6.25 or 15.6 mg a.i./rat on a shaved dorsal area ranging from 6.6% to
8.7% of the total body surface area. The rats were sacrificed 24 or
72 hours following application of the test material. Animals were
observed daily for toxic signs and mortality; body weight was measured
prior to dosing and at sacrifice on day 1 or day 3. Gross pathology
and histopathology were performed at sacrifice and plasma, RBC and
brain ChE activities were determined.
Three-fifths and 2/5 of female rats died during the 24 hour
exposure to methamidophos analytical grade and methamidophos technical
in the 15.6 a.i./rat dose groups, respectively. After 72-hour
exposure to methamidophos technical 1/5 females in the high dose group
died. No clinical signs of toxicity were observed at the lowest dose
group (1.0 mg a.i./rat). No compound related gross pathological
changes were noted at necropsy and no histopathological changes in the
skin were found. Dose-dependent significant cholinesterase inhibition
was observed in both males and females following treatment with both
test materials. For calculation of the dose the amount of active
ingredient was determined per cm2 total body surface area. ID50
values were determined to compare the relative sensitivities of each
tissue to cholinesterase inhibition. The lowest ID50 values were
observed in each tissue after 24 hours for both males and females.
RBC and plasma ChE were inhibited to a greater extent by the test
materials than brain ChE (see Table 2). No consistent difference in
cholinesterase inhibition was observed to be produced by either
methamidophos technical or analytical grade (Easter and Rosenberg,
1987).
Table 2. ID50 (µg a.i./cm2 total body surface area) 24 hrs.
after administration.
Test material RBC ChE Brain ChE Plasma ChE
males methamidophos
(analytical grade) 6.98 23.40 9.51
methamidophos
(technical) 10.00 18.55 5.85
females methamidophos
(analytical grade) 4.94 14.04 1.61
methamidophos
(technical) 5.41 8.33 0.57
Special study on pharmacokinetics
Male Wistar rats were given atropine sulfate (100 mg/kg i.p.) 10
to 15 minutes prior to i.v. dosing with 10 mg/kg methamidophos (purity
74%) in propylene glycol. At various time intervals after dosing
blood was taken and methamidophos values in plasma were analysed.
Pharmacokinetic values were calculated using a one compartment model:
t1/2 = 1.5 hr; Vd(volume of distribution)=0.81 L/kg; C1(clearance)=
5.8 mL/min/kg; kel(elimination constant)=0.45 hr-1. The volume of
distribution of 0.81 L/kg indicates that methamidophos is not highly
tissue bound (Eigenberg et al., 1983).
Toxicological studies
Acute toxicity studies
The acute toxicity of methamidophos is presented in Table 3.
Short-term studies
In a range finding study, groups of Wistar rats (10/sex/group)
were exposed to aerosols containing methamidophos (purity 75.7%) at
mean concentrations of 0 (vehicle=polyethylene glycol/ethanol), 1.4,
5.4 or 33.1 mg/m3 6 hours per day for 5 days.
The only effects observed were cholinergic signs and a
significant depression of cholinesterase activity in plasma and brain
as well as a reduced male body weight gain on day 5 occuring at 33.1
mg/m3 only. The NOAEL in this study was 5.4 mg/m3 (Pauluhn, 1987a).
Groups of Wistar rats (10/sex/group) were exposed to aerosols
containing methamidophos (purity 73%) at mean concentrations of 0
(air), 0 (vehicle=polyethylene glycol/ethanol), 2.6, 12.0 or 48.4
mg/m3 6 hours per day, 5 days per week over a period of 3 weeks
(head/nose exposure). Cholinergic symptoms were observed at 48.4
mg/m3. Body weight was slightly reduced in high dosed rats. Reduced
ALAT, urea and creatinine values were observed at 48.4 mg/m3.
Cholinesterase activities were significantly depressed in plasma
(35-88%), erythrocytes (20-25%) and in brain (20-74%) at 12.0 and 48.4
mg/m3. In the urine, acidification was observed at 48.4 mg/m3.
Relative adrenal weight was increased and relative thymus, liver and
spleen weight were decreased in high dose male rats. There were no
signs of specific organ damage or local damage to the respiratory
tract. The NOAEL in this study was 2.6 mg/m3 (Pauluhn, 1987b).
Groups of Wistar rats (10/sex/group) were exposed to 0 (air), 0
(vehicle=polyethylene glycol/ethanol), 1.1, 5.4 or 23.1 mg
methamidophos (purity 73.4%)/m3 6 hours per day, 5 days a week for 3
months. Two additional satellite groups (10/sex/group), of which one
was exposed to the vehicle aerosol and the other to 23.1 mg
methamidophos/m3, served as recovery groups with a 6-week exposure-
free recovery period. Observations included clinical signs, body
weight, haematology, biochemistry, urinalysis, cholinesterase
inhibition in plasma, erythrocytes and brain, lung function tests,
acetylcholine (ACH) provocation test, ophthalmoscopy, gross pathology,
organ weights and histopathology.
Table 3. Acute toxicity of methamidophos in animals.
Species Sex Route LD50 LC50 Purity Reference
(mg/kg b.w.) (mg/m3)
Rat M** oral 161 95.3% Flucke, 1990a
142 98.5%
163 97.8%
M, F Inhal. 213 75.7% Pauluhn, 1987a
(4 hr)
Hen F oral 48 72.5% Pauluhn and Kaliner, 1984
180*
oral 251# 95.3% Flucke, 1990b
432# 98.5%
823# 96.5%
dermal 50 74% Flucke, 1985
Turkey F Oral 15* 72.5% Pauluhn and Kaliner, 1984
Hen
1 test compound: (±)-methamidophos
2 test compound: (+)-methamidophos
3 test compound: (-)-methamidophos
* 50 mg atropine sulphate/kg b.w. was administered i.m. 5 min. before the test
compound.
** unfasted rats
# The enantiomers also differed in that the symptoms and recovery period lasted
longer, and mortalities occurred later with (-)-methamidophos that in the case
of (+)-methamidophos.
Cholinergic symptoms were observed at 23.1 mg/m3. In the same
dose group body weight as well as food consumption were significantly
reduced in both male and female rats. Ophthalmoscopy, haematology and
urinalysis were unremarkable. At 23.1 mg/m3 ASAT and LDH
concentrations were significantly increased in males. Protein,
cholesterol and glucose were significantly decreased in both high dose
male and female rats. Creatinine was significantly decreased at 5.4
and 23.1 mg/m3 in both sexes. Significant cholinesterase inhibition
(>30%) was observed in plasma and brain in rats at 5.4 and 23.1
mg/m3. Liver N-demethylase was significantly decreased in rats at
the highest dose level. The lung function tests performed at the end
of the exposure period gave no indications of functional lung damage.
In an acetylcholine provocation test, basal lung function parameters
were not changed but an increased reactivity of the bronchial
musculature to an acetylcholine aerosol was observed at dose levels of
5.4 mg/m3 and higher. In rats at 23.1 mg/m3, absolute and
relative spleen weight were significantly decreased, and relative
brain, and absolute and relative adrenal weight were increased, at the
same dose level. At gross pathology and histopathology no evidence of
treatment related organ damage or of local damage to the respiratory
tract was observed. A dose related increase in reticulum cells and an
increase in neutrophilic myelocytes in both male and female rats were
observed at 5.4 and 23.1 mg/m3 at the bone marrow morphological
examinations. At the end of the recovery period, changes in
biochemical parameters and cholinesterase returned to normal. The
NOAEL in this study is 1.1 mg methamidophos/m3 (Pauluhn, 1988).
Special studies on delayed neurotoxicity
Chickens
Acute neurotoxicity was studied in 30 adult Leghorn hens after
the simultaneous oral administration of 75 mg methamidophos and 400 mg
trimethylphosphate (TMPO)/kg bw, followed after 21 days by 50 mg
methamidophos and 264 mg trimethylphosphate/kg bw (both under atropine
protection). Two independent positive control groups of 5 hens were
administered 375 mg triorthocresylphosphate (TOCP)/kg bw once. The
negative control group received the solvents (water and polyethylene
glycol/ethanol for TMPO) under atropine protection twice at an
interval of 21 days. After the first administration of the
combination 15/30 hens died. No mortalities were observed after the
second administration. From the 27th post-observation day onwards,
7/15 surviving hens exhibited an incipient uncoordinated gait, but
progression was not observed. Delayed paralysis was not observed and
after morphological examination of the nerve tissues no indication for
induced neuropathy was provided. All hens in the positive control
group showed delayed paralysis and morphological nerve damage (Pauluhn
and Kaliner, 1984).
Groups of 3 hens received single oral doses of 0 (corn oil), 27.5
or 55 mg/kg bw methamidophos EC 63.3%. After 24 hours blood samples
were taken and the birds were killed and then brain, blood, liver,
heart, spleen and kidney tissues were collected for enzyme assays. No
effects were observed on the activity of glutathione-S-transferase
(GST) and brain neurotoxic esterase (NTE). Blood and heart
cholinesterase were inhibited, but acid phosphatase (AP) was increased
in brain, blood and liver tissues of the treated hens.
Another group of 10 hens received daily doses of 5.5 mg/kg
methamidophos EC 63.3% for 60 days, under atropine protection with an
observation period of 72 days. A control group received corn oil for
60 days. The hens were observed for any abnormalities in the ability
to walk or any clinical delayed neuropathic symptoms. Treated hens had
signs of cholinergic toxicity, especially in the first week of
treatment. Two and 3 hens died after 5 and 11 doses, respectively.
None of the surviving 5 hens showed signs of leg weakness or ataxia
throughout 60 days of the experiment or after 72 days (El-Sebae
et al., 1987).
The effect on neurotoxic esterase (NTE) was studied after dermal
application of 200 mg methamidophos (73.0%)/kg b.w. to 9 Leghorn
chickens under atropine protection. This dose represented 4 x the
LD50 without atropine protection. A positive control group and a
negative control group (9/group) received 100 mg TOCP/kg b.w. orally
and 5 ml Cremophor EL (2% v/v)/kg b.w. in demineralized water,
respectively. NTE activity in the nerve tissue (brain and spinal
cord) was determined after 24 and 48 hours and seven days post-
application in 3 chickens/group.
A mean inhibition of approximately 60% occurred in the brain
after 24 and 48 hours and approximately 46% in the spinal cord after
24 hours. An inhibition of over 80% in all cases in both nerve
tissues was observed in the positive controls at these times.
According to the authors an inhibition of 70-80% within 1-40 hours
after administration is necessary for induction of delayed neuropathy.
This threshold value was not reached after a dose of methamidophos
which was about 4 x the LD50 for dermal exposure (Flucke and Eben,
1988).
The effect on NTE in the nervous tissues and lymphocytes of hens
was also studied after the oral administration of 50 mg/kg b.w.
racemic methamidophos (purity 95.5%) and the enantiomers (+)- and (-)-
methamidophos (dose levels: 50, 100 or 400 mg/kg b.w. and 50, 200 or
400 mg/kg b.w., respectively) under atropine protection. The highest
doses of the (+) and (-) enantiomers were about 10 and 5 times the
LD50 respectively. NTE activity in brain, spinal cord, sciatic nerve
and lymphocytes was determined 24 and 48 hours and 7 days after
administration.
About 60-85% inhibition occurred in the brain and spinal cord
after administration of racemic methamidophos, which could be
reactivated. (+)- Methamidophos showed greater inhibition (up to 100%
in brain at 400 mg/kg b.w.) but nearly complete reactivation (>80%)
of the inhibited NTE occurred, whereas at 400 mg/kg bw (-)-
methamidophos up to 58 and 84% inhibition in brain after 24 and 48
hours, respectively, was observed, of which only a small fraction
could be reactivated. Irreversible NTE inhibition levels of nearly
90% to almost 100% were observed with TOCP, which was used as a
positive control, at oral doses of 100 and 300 mg/kg b.w. (Flucke and
Eben, 1990).
Two hundred mg/kg b.w. methamidophos (purity 74%) was dermally
applied twice at an interval of three weeks to 30 chickens under
atropine protection. A control group of 6 animals and a positive TOCP
group of 5 animals were also used. Ten of 30 chickens died after the
first treatment and one died after the second treatment. No delayed
neurotoxic damage was observed as confirmed by a negative clinical
test for neurotoxicity (forced movement) and the absence of basic
histomorphological variations between the chickens treated with
methamidophos and those in the negative control group. The TOCP group
developed neuropathy (Flucke and Kaliner, 1985).
Groups of white Leghorn hens (16/group) were orally administered
by gavage 0, 0.3, 1.0 or 3.0 mg methamidophos (purity 76%)/kg bw 5
days a week for 3 months. Ten hens/group were examined for delayed
neurotoxicity and plasma cholinesterase activity; NTE activities in
the brain and spinal cord were determined in 6 hens/group.
Two hens in the control group and 2 hens in the high dose group
died during the study (deaths were not considered to be
treatment-related). Somnolence and slight emaciation as well as a
decreased mean body weight were observed in hens at 3 mg/kg b.w., but
there were no signs of ataxia. Plasma cholinesterase (after 4 weeks)
and NTE activity in the spinal cord (after 12 weeks) were inhibited at
1 mg/kg bw (23 and 22%, respectively) and 3 mg/kg bw (48% and 41%,
respectively). NTE activity in the brain was only inhibited (17%) in
the highest dose group. No dose related effects including
neuropathological changes were observed grossly or microscopically.
The NOAEL for general toxicity and plasma cholinesterase and NTE
inhibition was 0.3 mg/kg bw/day (Sachsse et al., 1987).
Special studies on genotoxicity
The results of a cytogenetic assay in Chinese hamster ovary cells
and an unscheduled DNA synthesis test in rat primary hepatocytes are
described in Table 4.
Table 4. Results of genotoxicity assays on methamidophos.
Test system Test object Concentration Results Reference
Cytogenetics Chinese 3150,4200 and equivocal8 Murli, 1990
assay 1 hamster 5250 µg/ml2
ovary cells (without
action3)
1250,2500, negative
3750 and 4990
µg/ml (with
action4)
UDS assay Rat 0.001 to 10 negative Curren, 1988
hepatocytes µl/ml5,6,7
1 Both with and without rat liver S9 fraction
2 Test article purity = 74.5%
3 Mitomycin was used as positive control
4 Cyclophosphamide was used as positive control
5 Test article: Monitor technical (purity 71.2%)
6 Dose levels > 3.0 µl/ml were too toxic to be evaluated for UDS.
7 7,12-dimethylbenz(a)anthracene was used as a positive control
8 Slight increases in chromosome aberations were found at cytotoxic doses
Special studies on skin sensitization
Repeated application (via a modified Buehler method) of
methamidofos technical (purity 73.8%) at a concentration of 25% w/w in
distilled water to the shaven backs of Hartley guinea pigs did not
cause allergic sensitization (Cushman, 1984).
Observations in humans
Cholinesterase inhibition
In an oral dosing study, human volunteers were given combinations
of acephate and methamidophos. Groups of 3 males and 3 females
received 0.1, 0.2, or 0.3 mg/kg bw/day of a methamidophos/acephate
combination (1:9) for 21 days followed by a 7-day recovery period
after which the dose for each group was increased to 0.4 mg/kg bw/day
(females only) for 10 days. Groups of 2 males and 2 females received
0.1 or 0.2 mg/kg bw/day of a methamidophos/acephate combination (1:4)
for 21 consecutive days. In none of the groups was any effect noted on
erythrocyte cholinesterase. Plasma cholinesterase activity was
affected in the 1:9 groups in males at 0.3 mg/kg bw/day and only
slightly in females at 0.4 mg/kg bw/day. Plasma cholinesterase
inhibition in the 1:4 group was observed at 0.2 mg/kg bw/day. The
NOAEL in this study was 0.3 mg/kg bw/day for the combination 1:9 and
0.2 mg/kg bw/day for the combination 1:4, with methamidophos
concentrations of 0.03 and 0.04 mg/kg bw/day, respectively (Garofalo,
1973). The raw data were validated and support the above conclusions
regarding cholinesterase activities. Acephate and methamidophos were
detected in urine and blood from the subjects, but urine samples were
only collected periodically and excretion data were not calculated
(Cavalli, 1978).
Information was obtained from the manufacturer concerning 36
cases of intoxication by methamidophos in the Federal Republic of
Germany during 1978-1982. These were mainly the result of misuse of
the compound (painting hop poles). Efficient warnings prevented
further accidents. These cases could not be used for evaluation of a
delayed haemotoxic potential because not enough information was
available (Machemer, 1988).
COMMENTS
An in vitro experiment found that methamidophos inhibited
cholinesterase at a much higher rate than acephate. The I50 for human
erythrocyte cholinesterase and rat brain cholinesterase were of the
same order of magnitude.
Delayed neurotoxicity has been studied in hens following oral and
dermal exposures. Methamidophos inhibited NTE and elicited signs of
delayed neuropathy at dose levels which were higher than the LD50,
indicating that the potential to induce delayed neuropathy was low.
A NOAEL of 0.3 mg/kg bw/day was demonstrated in a 90-day oral
neurotoxicity study in hens.
Inhibition of erythrocyte cholinesterase was not found in a
short-term study in humans in which dose levels up to 0.3 mg/kg bw/day
of a combination of one part methamidophos with nine parts acephate or
0.2 mg/kg bw/day of a combination of one part methamidophos with four
parts acephate were given. The estimations of the NOAEL for
methamidophos in this study were 0.03 and 0.04 mg/kg bw/day,
respectively. These data from humans were used in allocating the ADI.
In allocating the ADI it was assumed that the effects observed after
administration of the mixture were due solely to methamidophos.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect
Rat: 2 ppm in the diet, equal to 0.1 mg/kg bw/day
Dog: 2 ppm in the diet, equal to 0.06 mg/kg bw/day
Chicken: 0.3 mg/kg bw/day
Human: 0.04 mg/kg bw/day
Estimate of acceptable daily intake for man
0-0.004 mg/kg b.w.
Studies which will provide information valuable in
the continued evaluation of the compound
Further observations in humans.
REFERENCES
Cavalli, R.D. (1978) Data validation Industrial Bio-Test report no.
636- 02498. A study on the effects of orthene and monitor on plasma
and erythrocyte cholinesterase activity in human subjects during
subacute oral administration. Submitted to WHO by Chevron Chemical
Company, Richmond, CA, USA.
Curren, R.D. (1988) Unscheduled DNA synthesis in rat primary
hepatocytes. Test article: Monitor technical. Unpublished report no.
1119, from Microbiological Associates, Inc. Submitted to WHO by Bayer
AG, Leverkusen, Germany.
Cushman, J.R. (1984) Modified Buehler test for the skin sensitization
potential of methamidophos technical (SX-1490). Unpublished
toxicological report no. 596 from Chevron Environmental health Center,
Richmond, California, USA. Submitted to WHO by Bayer AG.
Easter, M.D. and Rosenberg, D.W. (1986) The cholinesterase inhibition
potential of analytical grade methamidophos (SX-1672) and
methamidophos technical (SX-1490) following topical application of a
single dose to male and female rats. Unpublished toxicological report
SOCAL 2211 from Chevron Environmental Health Center, Richmond
California, USA. Submitted to WHO by Bayer AG.
Eigenberg, D.A., Pazdernik, T.L. and Doull, J. (1983) Haemoperfusion
and pharmacokinetic studies with methamidophos in the rat. Fund. Appl.
Toxicol., 3, 490-501.
El-Sebae, A.H., Ahmed, N.S., El-Gendy, K.S., El-Bakary, A.S. and
Soliman, S.A. (1987) Methamidophos (Tamaron) - a delayed neuropathic
compound to man, but negative to chickens. Proc. 2nd Nat. Conf. on
Pests and Dis. of Veg. and Fruits, Ismailia, Egypt, October, 1987,
475-485.
Flucke, W. (1985) SRA 5172 TA (Tamaron TA) (c.n. methamidophos) Study
for acute dermal toxicity to the chicken (Gallus domesticus).
Unpublished toxicological report no. 13780 from Institute of
toxicology Bayer AG. Wuppertal-Elberfeld. Submitted to WHO by Bayer
AG.
Flucke, W. (1990a) Methamidophos (Tamaron): Racemate and Enantiomers.
Study for acute oral toxicity to rats. Unpublished report 19034 from
Bayer AG, Fachbereich toxicologie, Wuppertal. Submitted to WHO by
Bayer AG.
Flucke, W. (1990b) Methamidophos (Tamaron): Racemate and enantiomers.
Study for acute oral toxicity to the hen (Gallus domesticus).
Unpublished report 19091 from Bayer AG, Fachbereich toxikologie,
Wuppertal. Submitted to WHO by Bayer AG.
Flucke, W. and Eben, A. (1988) SRA 5172 TA (Tamaron TA) - Study for
the effect on the neurotoxic esterase (NTE) after dermal
administration to chickens. Unpublished toxicological report no.
17268 from Bayer AG Toxicology division, Wuppertal. Submitted to WHO
by Bayer AG.
Flucke, W. and Eben, A. (1990) Methamidophos: racemate and
enantioners. Study for effect on NTE (neuropathy target esterase) in
hens following oral administration. Unpublished report no.: 19092
from Bayer AG Fachbereich Toxikologie, Wuppertal. Submitted to WHO by
Bayer AG.
Flucke, W. and Kaliner, G. (1985) SRA 5172 TA (Tamaron TA) (c.n.
methamidophos) Study for acute neurotoxicity to the chicken after
dermal administration. Unpublished report no. 13852 from Bayer AG
Institute of toxicology. Submitted to WHO by Bayer AG.
Garofalo, M. (1973) A study on the effects of orthene and monitor on
plasma and erythrocyte cholinesterase activity in human subjects
during subacute oral administration. Industrial Bio-Test Laboratories,
Inc. unpublished report no. 636-02498. Submitted to WHO by Chevron
Chemical Company, Richmond, CA, USA. Validated by United States
Environmental Protection Agency.
Hussain, M.A., Mohamad, R.B. and Oloffs, P.C. (1985) Studies of the
toxicity, metabolism, and anticholinesterase properties of acephate
and methamidophos. J. Environ. Sci. Health. B20(1), 129-147.
Machemer, L. (1988) Expertise on the question: Does methamidophos
induce delayed neuropathy? Unpublished report (January 8, 1988) from
Bayer AG Fachbereich Toxikologie, Wuppertal. Submitted to WHO by Bayer
AG.
Murli, H. (1990) Mutagenicity test on SRA 5172 in an in vitro
cytogenetic assay measuring chromosomal aberration frequencies in
chinese hamster ovary (CHO) cells. Unpublished report no. R4935 from
Hazleton Laboratories America, Inc. Submitted to WHO by Bayer AG.
Pauluhn, J. (1987a) SRA 5172 TA (c.n. methamidophos) Study for acute
inhalation toxicity to the rat to OECD guideline no. 403. Unpublished
report no. 15661 from Bayer AG Institute of Toxicology, Wuppertal.
Submitted to WHO by Bayer AG.
Pauluhn, J. (1987b) SRA 5172 (Common name: methamiphos, the active
integredient of MonitorR) Study of the subacute inhalation toxicity
to rats in accordance with OECD guideline no. 412. Unpublished report
no. 16069 from Bayer AG Fachbereich toxikologie, Wuppertal. Submitted
to WHO by Bayer AG.
Pauluhn, J. (1988) SRA 5172 (Common name methamidophos, the active
ingredient of MonitorR) Study of the subchronic inhalation toxicity
to rats in accordance with OECD guideline no. 413. Unpublished report
no. 16578 from Bayer AG Fachbereich toxikologie, Wuppertal. Submitted
to WHO by Bayer AG.
Pauluhn, J. and Kaliner, G. SRA 5172 and trimethylphosphate (TMPO)
(c.n. methamidophos) Study for the combination's acute neurotoxicity
to hens and turkey hens. Unpublished report no. 13056 from Bayer AG
Institute of toxicology, Wuppertal. Submitted to WHO by Bayer AG.
Pauluhn, J., Machemer, L and Kimmerle, G. (1987) Effects of inhaled
cholinesterase inhibitors on bronchial tonus and on plasma and
erythrocyte acetylcholine esterase activity in rats. Toxicology 46,
177-190.
Sachsse, K., Oharek, A., Zbinden, K., Madoerin, K., Luetkemeier, H.,
Wilson, J., Terrier, Ch. and Vogel, W. (1987) 3-Month subchronic
delayed neurotoxicity study with SRA 5172 (c.n. methamidophos) in the
hen. Unpublished report no.: R 4106 from RCC AG, Switzerland.
See Also:
Toxicological Abbreviations
Methamidophos (HSG 79, 1993)
Methamidophos (ICSC)
Methamidophos (JMPR Evaluations 2002 Part II Toxicological)
Methamidophos (Pesticide residues in food: 1976 evaluations)
Methamidophos (Pesticide residues in food: 1979 evaluations)
Methamidophos (Pesticide residues in food: 1981 evaluations)
Methamidophos (Pesticide residues in food: 1982 evaluations)
Methamidophos (Pesticide residues in food: 1984 evaluations)
Methamidophos (Pesticide residues in food: 1985 evaluations Part II Toxicology)