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
PARATHION METHYL
Explanation
Parathion Methyl was evaluated by the Joint Meeting in 1968,
1972, 1975, 1979 and 1980 (FAO/WHO 1969, 1973, 1976, 1980, 1981). A
temporary ADI of 0-0.001 mg/kg bw was allocated in 1980. New data were
presented to the JMPR in 1982, including mutagenicity data, a
3-generation reproduction study and data from a two-year rat feeding
study. However, since the available oncogenicity data did not permit a
complete evaluation of the carcinogenic potential of parathion methyl
the meeting extended the temporary ADI and requested additional data
on the two-year feeding study in rats by 1984. Additional information
is reviewed in this monograph addendum.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
TOXICOLOGICAL STUDIES
Special Studies on Carcinogenicity
Rat
Additional data on a 2-year feeding study in rats as requested by
the Joint Meeting in 1982 (FAO/WHO 1983) were available. Historical
data on the incidence of follicular and parafollicular thyroid
adenomas as well as uterine adenocarcinomas in SPF Wistar TNO/W74 rats
used in previous report (Bomhard et al., 1981) have been provided.
Tumours of the same type in both thyroid lobes were counted as
being one tumour. The incidence of thyroid carcinomas were also
included. The historical control data were collected from 15
experiments. The thyroid and uterine tumour incidence of the high dose
group (50 ppm) is within the range of the historical controls. Only
fifty percent of the control animals from Bomhard et al., 1981, study
were examined histologically.
Histological examination of the 2 and 10 ppm dose groups were
performed and these data were presented as well. In both groups there
were no pathomorphological indications of compound related effects on
the organ systems evaluated. Type and location of benign and malignant
tumours did not demonstrate an oncogenic effect from parathion methyl
as they were randomly distributed and within the normal range for this
strain of rat (Schilde and Bomhard, 1984).
Acute Toxicity
The acute toxicity of parathion methyl via oral and dermal routes
is summarized in Table 1.
TABLE 1: Acute Toxicity of Parathion Methyl
Species Sex Route LD50 Reference
Rat (fasted) M Oral 2.9 mg/kg Heiman, 1982
F Oral 3.2 mg/kg Heiman, 1982
Rat M Oral 10.8 mg/kg Heiman, 1982
(non-fasted) F Oral 9.3 mg/kg Heiman, 1982
Rabbit M Oral 10.0 mg/kg Heiman, 1982
(fasted) F Oral 19.4 mg/kg Heiman, 1982
Rat M Dermal 46.0 mg/kg Heiman, 1982
F Dermal 41.0 mg/kg Heiman, 1982
Special Study on Eye and Skin Irritation
Instillation of 0.1 g of parathion methyl into the conjunctival
sac of albino rabbits did not produce irritation.
Application of 0.5g of parathion methyl (as a wet paste) to the
skin of albino rabbits did not produce primary skin irritation
(Pauluhn, 1983).
Short-term Studies
Rabbit - Dermal
Groups of New Zealand white rabbits (6 males and 6 females per
group) were administered parathion methyl (purity 96.3%) dermally at
dose levels of 0, 50 and 250 mg/kg bw formulated in Cremophor E.I.,
applied daily for 3 weeks (15 consecutive workdays). Material was left
uncovered for 6 hours. The skin was then cleaned with soap and water.
There was a dose-related inhibition of erythrocyle and brain
cholinesterases in both dose groups. Plasma cholinesterase was also
significantly depressed in the high dose group. These animals
presented symptoms of cholinergic poisoning and 5 animals in this
group died. The results of the remaining clinical chemistry,
hematological evaluations and organ weight data did not demonstrate
significant differences from controls. Microscopic examination
revealed epithelial proliferation with hyperkeratosis of the treated
skin.
Since a no effect level was not established a separate three-week
dermal study was initiated using 0 and 10 mg/kg bw. No signs of dermal
involvement or proliferative changes were noted and cholinesterase
levels were comparable to controls (Mihail and Vogel, 1984).
Rat - Inhalation
Groups of Wister albino rats (10 males and 10 females per group)
were exposed to parathion methyl aerosol concentrations of 0 (solvent
only), 0.9, 2.6 and 9.7 mg per 120 m air. Animals were exposed for
6 hours/day, 5 days/ week for 3 consecutive weeks. No mortality
occurred. Plasma and brain cholinesterase levels were significantly
depressed in high dose groups animals. They presented signs of
cholinergic poisoning, reduced body weight gain and decreased organ
weights. The mid dose group presented slight inhibition of plasma
cholinesterase levels. Histopathological examinations were
unremarkable between treated and control groups (Thyssen and Mohr,
1982).
COMMENTS
Parathion methyl was allocated a temporary ADI of 0-0.001 mg/kg
by the 1980 JMPR. New data were presented at the 1982 JMPR including a
two-year rat study but as this did not allow full evaluation of the
carcinogenic potential of parathion methyl, or permit a no-effect
level to be established, the temporary ADI was extended and additional
data were requested from the two-year rat study by 1984.
Re-evaluation of these data, the additional data requested and
now provided, and carcinogenicity studies of parathion methyl in mouse
and rat of the National Cancer Institute (1979) have indicated no
evidence of carcinogenicity and have allowed the calculation of a
no-effect dose in the two-year rat feeding study of 2 ppm in respect
to terminal brain cholinesterase, plasma and erythrocyte
cholinesterasis. This allowed the allocation of a full ADI, based
partly on data in man (see 1975 JMPR).
Level causing no toxicological effect
Rat: 2 ppm in the diet equivalent to 0.1 mg/kg bw
Man: 0.3 mg/kg bw/day
Estimate of acceptable daily intake for man
0 - 0.02 mg/kg bw
FURTHER WORK OR INFORMATION
Desirable:
Further observations in man.
REFERENCES
Bomhard, E., Loser, E., and Schilde, B. (1981) E605-Methyl
(parathion-methyl) chronic toxicological study on rats (feeding
experiment of two years). Report submitted to the World Health
Organization by Bayer AG. (Unpublished)
Bomhard, E. (1984). Ref: Parathion Methyl/report no. 9889: WHO
requirements. Report submitted to the World Health Organization
by Bayer AG. (Unpublished)
Heinmann, K.G. (1982). E 120 (Parathion-Methyl)/Tests for acute oral
and acute dermal toxicity. Report submitted to the World Health
Organization by Bayer AG. (Unpublished)
Mihail, F. and Vogel, O. (1984). E 120 (Parathion-Methyl)/Subacute
dermal toxicity studies with rabbits. Report submitted to the
World Health Organization by Bayer AG.(Unpublished)
NCI, (1979). Bioassay of Methyl Parathion for possible carcinogenicity
study. D.H.E.W. publication NCI-CG-TR-157. National Institutes of
Health Bethesda M.D.
Pauluhn, J. (1983). Parathion Methyl (E 120)/Study for
irritant/corrosive effect on skin and eye (Rabbits). Report
submitted to the World Health Organization by Bayer AG.
(Unpublished)
Schilde, N. and Bomhard, E. (1984). E 605-methyl (Parathion Methyl)
/Supplementary histopathological examination for the two year
feeding study with rats (addendum to Rep. No. 9889). Report
submitted to the World Health Organization by Bayer AG.
(Unpublished)
Thyssen, J. and Mohr. U. (1982). E 120 (Parathion Methyl) /Subacute
inhalation study with rats. Report submitted to the World Health
Organization by Bayer AG. (Unpublished)