PESTICIDE RESIDUES IN FOOD - 1979
Sponsored jointly by FAO and WHO
Joint meeting of the
FAO Panel of Experts on Pesticide Residues
in Food and the Environment
WHO Expert Group on Pesticide Residues
Geneva, 3-12 December 1979
Parathion methyl was evaluated by the meeting in 1968 and reviewed in
1972 and 1975. Studies on teratogenesis and on reproduction in
species appropriate to such tests were required by the 1975 Meeting.
In addition, long-term studies in at least one mammalian species were
indicated to be desirable.
New data on teratogenicity were available to the Meeting, and are
reviewed in this monograph addendum.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
Special Studies on Teratogenicity
Parathion methyl (in 10 percent DMSO) was used in a chick embryo
screening test. Single doses of 3, 30 and 100 µg were administered
subgerminally on day 2 and intraamniotically on days 3 and 4. These
treatments induced no specific malformations. Embryotoxicity was
noted only in the two high doses (30 and 100 µg) (Benes and Jelinek,
Parathion methyl was orally administered by gavage to groups of female
rats (20-24 rats/group) during pregnancy from day 6 to day 15 of
gestation at dosage levels of 0, 0.1, 0.3 and 1 mg/kg. On day 20 of
pregnancy, the animals were sacrificed, the foetuses removed, and the
following parameters examined: number and weight of litters, number
and mean weight of foetuses, fetal sex, weight of placenta, number of
implantations, resorptions and dead embryos, and external and internal
defects including skeletal abnormalities. A modified Wilson procedure
was used for determining visceral malformations. Skeletal defects
were assessed by Alizarin red staining. Weight gain in mothers and a
slight retardation of growth in foetuses was noted at the highest dose
level. This maternally toxic effect was attributed to the fact that
the high dose of 1 mg/kg is close to the acutely toxic dose for rats.
Parathion methyl was not toxic to the embryo or foetus and there was
no apparent teratogenic effect noted (Machemer, 1977a).
Groups of female rats (24-26 rats/group) were injected intravenously
with parathion methyl from day 6 to day 15 of pregnancy at dosage
levels of 0, 0.03, 0.1 and 0.3 mg/kg body weight. The methods
employed and parameters examined were the same as previously reported
in the oral application study. None of the doses were toxic for dams
and parathion methyl did not affect the development of the embryo
(Machemer, 1977b). With both oral and intravenous administration,
parathion methyl was not teratogenic.
Some of the studies required by the 1975 Meeting became available and
were evaluated. Teratogenicity studies in rats indicated neither
teratogenic nor embryo-toxic effects of oral and intravenous exposure.
The meeting was informed that the previously-requested studies were in
progress, and decided to extend the temporary acceptable daily intake.
Level Causing No Toxicological Effect
Man: 0.3 mg/kg body weight
ESTIMATE OF TEMPORARY DAILY INTAKE FOR MAN
0-0.001 mg/kg body weight
FURTHER WORK OR INFORMATION
Required by June 1982:
1. Reproduction study in species appropriate to such test;
2. Adequate long-term study reported to be in progress.
Benes, V. and Jelinek, R. Embryotoxicity of Parathion Methyl with the
Chick Embryo-toxicity Screening Test (CHEST). (1979) Unpublished
report from Institute of Hygiene and Epidemiology, Prague.
Machemer, L. Parathion Methyl. Untersuchungen auf Embrotoxische und
Teratogene Wirkungen an Ratten Nach Oraler Verabreichung. (Parathion
Methyl. Evaluation for Embryotoxic and Teratogenic Effects on Rats
following Oral Administration). (1977a) Unpublished report from
Institut für Toxikologie, submitted by Bayer AG.
Machemer, L. Parathion Methyl. Untersuchungen auf Embrotoxicische
und Teratogene Wirkungen an Ratten Nach Intravenöser Injection.
(Parathion Methyl. Evaluation for Embryotoxic and Teratogenic Effects
on Rats Following Intravenous Injection). (1977b) Unpublished report
from Institut für Toxikologice, submitted by Bayer AG.