PESTICIDE RESIDUES IN FOOD - 1981
Sponsored jointly by FAO and WHO
Food and Agriculture Organization of the United Nations
FAO PLANT PRODUCTION AND PROTECTION PAPER 42
pesticide residues in food:
data and recommendations
of the joint meeting
FAO panel of experts on pesticide residues
in food and the environment
WHO expert group on pesticide residues
Geneva, 23 November-2 December 1981
FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS
In 1975, the Joint Meeting evaluated sec-butylamine. A temporary
ADI (0-0.1 mg base/kg bw) wag allocated.*
Further work or information required by 1981 (FAO/WHO 1979)
included the following: required by 1981: (1) further studies to
resolve the question of carcinogenic risk; desirable: (1)
quantitative metabolic studies to determine whether metabolites in
test animals are the same as those in food, plants and animals; (2)
information on the formation and, if found, toxicity of potential
nitrosated derivatives; (3) mutagenicity studies with techniques
currently available and (4) clinical and metabolic observations in
Of the remaining required and desirable information, only
information on mutagenesis for sec-butylamine has been received for
evaluation in 1981.
DATA FOR THE ESTIMATION OF ACCEPTABLE DAILY INTAKE
Special studies on mutagenicity
A recent study examined sec-butylamine and sec-butylamine
+ H3PO4 for mutagenic activity. Tests included Escherichia coli
WP2 and the standard Salmonella/microsome assay with Salmonella
typhimurium strains TA 1535, 1537, 1538, 98 and 100, as well as the
induction of mitotic recombination in the yeast S. cerevisiae D3. Each
assay was performed with or without a rat liver S9 mix for metabolic
activation. Neither sec-butylamine nor sec-butylamine + H3PO4
exhibited a mutagenic or recombinogenic response in these systems
(Mortelmans and Riccio 1980).
The compound was tested in S. typhimurium and E. coli WP2
over a range of 0.1 to 50.0 Ál/plate (about 0.07 to 36.5 mg/plate,
density approx. or = 0.73) and retested at doses ranging from 0.1 to
25.0 Ál/plate (approx. 0.07 to 18.3 mg/plate). No reproducible, dose-
related increases in the number of revertants was observed. Toxicity
was seen with all strains at 25.0 Ál/plate except for WP2, which
showed toxicity at 50.0 Ál/plate. No recombinogenic activity was
* See Annex II for FAO and WHO documentation.
observed with this compound when it was tested in S. cerevisiae D3
over concentrations ranging from 0.05 to 0.5% and retested from 0.05
to 0.18%. Toxicity was observed at 0.2% without metabolic activation
and at 0.3% with metabolic activation.
In another Salmonella and E. coli WP2 assays, the compound
was first tested over a concentration range of 1 to 100 Ál/plate. A
second experiment was conducted over the same range for all strains
except TA 98 and TA 100, which were tested up to 500 Ál/plate. This
was due to the shortage of samples remaining and the desirability of
testing this toxicity with strains of TA 98 and TA 100. A toxic
response was obtained at the concentration of 500 Ál/plate with these
two strains, both with and without metabolic activation.
In another S. cerevisiae D3 assay, the compound was first
tested at concentrations ranging from 0.1 to 5.0% and then retested at
higher concentrations ranging from 1.0 to 7.5%. No reproducible, dose-
related increase in the number of mitotic recombinants was observed
(Mortelmans and Riccio 1980).
Although data were received pertaining to mutagenic potential of
sec-butylamine, they were deemed to be insufficient to permit
assessment of carcinogenic risk. Thus, although data was received that
alleviated doubts regarding genotoxic potential, the overall concern
regarding the carcinogenic potential of sec-butylamine remains
As sec-butylamine is a primary amine, the possibility of
nitrosamine formation was considered to be remote.
Concern regarding this compound, although reduced, has not been
eliminated. The temporary ADI of 0.01 mg free amine/kg bw/day was
extended for a further three years.
Level causing no toxicological effect
Rat: 686 ppm free amine (1250 ppm acetate salt in the diet),
equivalent to 35 mg free amine/kg bw/day (63 mg acetate salt/kg
Dog: 69 mg free amine/kg bw/day (125 mg acetate salt/kg bw/day).
Estimate of temporary acceptable daily intake for mail
0 - 0.1 mg free amine/kg bw.
FURTHER WORK OR INFORMATION
Required (by 1984)
1. Further studies to resolve the question of carcinogenic
1. Adequate toxicological studies on a non-rodent species.
2. Clinical and metabolic observations in humans.
Mortelmans, K. and Riccio, E.S. In vitro microbiological genotoxicity
1980 assay of acetonitrile, sec-butylamine (2-AB) and sec-
Butylamine (2-AB) + H3PO4. SRI International Project
LSU-7558-24. Contract No. 68-02-2947, Final Report, March