PESTICIDE RESIDUES IN FOOD - 1984
Sponsored jointly by FAO and WHO
EVALUATIONS 1984
The monographs
Data and recommendations of the joint meeting
of the FAO Panel of Experts on Pesticide Residues
in Food and the Environment and the
WHO Expert Group on Pesticide Residues
Rome, 24 September - 3 October 1984
Food and Agriculture Organization of the United Nations
Rome 1985
PHOXIM
Explanation
Phoxim was evaluated by the Joint Meeting in 1982 1/ and a
temporary ADI was allocated. An appropriate neurotoxicity study in
hens was required and has now been submitted, together with an
additional embryotoxicity teratogenicity study in rabbits. These data
are reviewed in this monograph addendum.
Corrigenda: The 1982 Evaluations, page 380, misreported the
temporary ADI of 0-0.05 mg/kg bw. The 1982 Report correctly stated the
temporary ADI as 0-0.0005 mg/kg bw.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
TOXICOLOGICAL STUDIES
Special Study on Embryotoxicity and Teratogenicity
Rabbit
Groups of 20 mated female chinchilla rabbits received, by gavage,
daily doses of Phoxim (technical grade, 83.8 percent pure) at levels
of 0, 12, 36 or 72 mg/kg bw/day, from day 6 through day 18 of
pregnancy. On day 28 of pregnancy, dams were killed and foetuses
removed by caesarean section for external, visceral and skeletal
examination. No dose-related mortality was observed. Compound-related
symptoms were observed in the high dose group only. In the dams,
Phoxim caused a reduction of food consumption and mean body weight
gain which were slight at 36 mg/kg and marked at 72 mg/kg. The number
of pregnant females, pre-implantation losses, implantations per dam,
live foetuses and sex ratio of live foetuses were comparable among all
groups. An increased ratio of embryonic resorption and decreased mean
body weight of foetuses were observed in the high dose group compared
to the control and other treated groups. The no-effect level for
embryotoxicity is 36 mg/kg bw. No malformations or anomalies
attributable to the treatment were observed (Becker, 1982).
Special Study on Delayed Neurotoxicity
Thirty white Leghorn hens, 10-15 months old, received, by gavage,
Phoxim at a dose level of 50 mg/kg bw, protected with atropine
(50 mg/kg bw). After an interval of 21 days, the same procedure was
repeated. The dose of 50 mg/kg bw of Phoxim administered in a pilot
study produced 80 percent mortality when given without atropine
protection. A negative control group of six hens received the same
quantity of vehicle solution and atropine. A positive control group of
five hens received a single dose of 375 mg/kg bw of
triorthocresyl-phosphate (TOCP).
1/ See Annex 2 for FAO and WHO documentation.
At the end of the observation period (42 days after the first
administration for compound and solvent-treated hens, 24 days for
TOCP-treated hens), the animals were sacrificed and sciatic nerve
tissue was removed for histopathological examination.
In the compound-treated group, after the end of the acute phase
of poisoning, the hens were free of effects up to the time of the
repeated administration. Signs similar to paralysis, disturbance of
coordination of movement and protracted effects were not observed at
any time during the observation period. The histopathological
examinations also showed that no treatment-induced peripheral
neuropathy or demyelinization had been induced. All hens in the
positive control (TOCP) group showed progressive disturbance of
coordination of movement with severe paralysis in the final stage;
histopathological examination revealed varying degrees of nerve fibre
degeneration in the peripheral nerve (demyelinization, lysis of axon,
ballooned fibre segments, activated Schwan cells). Phoxim did not
produce neurotoxic effect, as determined in this study. (Pauluhn &
Kaliner, 1984).
The acute oral LD50 to hens (15-20 months old) was determined to
be 40 mg/kg bw (Pauluhn, 1983).
COMMENTS
Phoxim was evaluated in 1982, when a temporary ADI was allocated
and an appropriate neurotoxicity study in hens was required. Phoxim
did not display delayed neurotoxicity effects in a double-dose test in
hens. No teratogenic effects were observed in rabbits. The temporary
ADI was changed to a full ADI.
TOXICOLOGICAL EVALUATION
Level Causing no Toxicological Effect
Rat: 5 ppm in the diet, equal to 0.56 mg/kg bw
Dog: 2 ppm in the diet, equivalent to 0.05 mg/kg bw
Estimate of Acceptable Daily Intake in Man
0 - 0.001 mg/kg bw
FURTHER WORK OR INFORMATION
Desirable
1. Observations in humans (particularly effects on cholinesterase).
2. Type and content of impurities in the technical products.
REFERENCES
Becker, H. Embryotoxicity and teratogenicity study on SRA 7502 in
1982 Rabbits. Report No. R 2354 from Research & Consulting
Company Ltd., Switzerland, submitted by Bayer AG to WHO.
(Unpublished)
Pauluhn, J. SRA 7502 (Active ingredient of Baythion and Volaton) -
1983 Acute oral toxicity study on hens. Report No. 11978 from
Institute of Toxicology, Bayer, submitted by Bayer AG to
WHO. (Unpublished)
Paulunh, J. & Kaliner, G. SRA 7502 (c.n.: phoxim) - Study of acute
1984 neurotoxicity in hens. Report No. 12632 from Institute of
Toxicology, Bayer, submitted by Bayer AG to WHO.
(Unpublished)