PESTICIDE RESIDUES IN FOOD - 1984
Sponsored jointly by FAO and WHO
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
Phenthoate was evaluated by the Joint Meeting on Pesticide
Residues in 1980 (FAO/WHO 1981) at which time only a temporary ADI was
allocated on the basis that a chronic toxicity in a rodent was needed.
The required chronic toxicity/carcinogenicity study has been submitted
and is summarized in this monograph addendum.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
Special Studies on Carcinogenicity
(see under long-term studies)
Groups of Sprague-Dawley rats (60 males and 60 females per group)
were fed diets containing Phenthoate (technical grade, 93.9 percent
purity at levels of 0, 20, 100 or 500 ppm for 116 weeks.
Animals were observed three times a day for morbidity and
mortality. Food and water consumption, body weights and adverse
clinical (including neurological, ocular and behavioural) signs were
recorded weekly for the first 13 weeks and bi-weekly thereafter. At
periodical intervals haematology, clinical chemistry (including
cholinesterase activity) and urine analyses were performed on ten
animals/group/sex. Gross pathology and histopathology examinations
were performed on all animals.
No clinically detectable pathological signs were observed. There
were no significant differences between control and treated groups
with respect to mortality, growth, food and water consumption,
haematology, clinical chemistry (except cholinesterase activity) and
urine analyses. Plasma cholinesterase activity was significantly
depressed in males and females of the 500 ppm group from week 26 to
termination and in females at 100 ppm from week 78. Erythrocyte
cholinesterase depression from 22-25 percent for females and 12-19
percent for males, in the 20 ppm group as compared to the control and
is considered the marginal effect level. Brain cholinesterase activity
was depressed about 20 percent in the high-dose group only.
Absolute and relative organ weights were not significantly
different between control and treated groups. No specific gross
pathological changes attributable to the treatment were noted.
Histopathologically, nodular hyperplasia of hepatic cells was
significantly increased, although not dose-related, in treated groups
when compared to the controls.
There were no statistically significant differences between
control and treated groups with respect to type, incidence,
distribution or latency time of observed tumours. Under the conditions
of the test, phenthoate did not display any carcinogenic potential.
Detailed histopathological examinations performed to assess the
potential neurotoxic effects of phenthoate did not reveal any lesions.
Phenthoate was evaluated in 1980 when a temporary ADI was
In the rat long-term toxicity/carcinogenicity study submitted,
phenthoate did not show oncogenic potential. No changes in
haematology, clinical chemistry or urine analyses, nor any lesions in
nervous tissues examined, were observed. The 20 ppm dose level was
identified as producing a marginal effect on erythrocyte cholinestase
in this study. The meeting allocated a full ADI.
Level causing no toxicological effect
Dog: 10 ppm in the diet, equal to 0.29 mg/kg b.w.
Rat: 10 ppm in the diet, equal to 1.0 mg/kg b.w.
Mouse: 30 ppm in the diet, equivalent to 4.5 mg/kg b.w.
Estimate of acceptable daily intake for humans
0 - 0.003 mg/kg b.w.
Further work or information
Observation in humans.
Further information on impurities in the technical products in
order to evaluate the degree to which these impurities affect the
acute toxicity of phenthoate.
Maltoni, C. Long-term carcinogenicity and chronic toxicity of
1984 phenthoate (CAS No.2597-03-7) on Sprague-Dawley rats (oral
dosing study) Bologna, Italy. Inst. Oncology. Report No. BT
5005. Submitted by Farmoplant, Italy, to WHO.