234. Crufomate (WHO Pesticide Residues Series 2)

CRUFOMATE JMPR 1972

Explanation

This insecticide was previously evaluated in 1968 (FAO/WHO, 1969) at
which time an acceptable daily intake and temporary tolerances were
recommended. Four requirements for further work or information were
set forth. Since the previous evaluation, additional data and
information have become available.

At the Sixth Session of the Codex Committee on Pesticide Residues, it
was requested that the Joint Meeting clarify the question of the
distribution of the pesticide between the fat and aqueous phase of
meat.

RESIDUES IN FOOD AND THEIR EVALUATION

Fulfillment of requirements

In the following paragraphs, the numbers refer to the corresponding
requirement set forth by the 1968 Joint Meeting.

1. Data from countries other than the United States of America and
the United Kingdom on use pattern and residues

No data were available from countries other than U.S.A. and U.K.
However, the manufacturer gave written assurance that the main
uses were only in these two countries (Dow Chemical Co., 1972).
New data were supplied which gave more details on use patterns
and withdrawal periods recommended, which are summarized in the
following sections.

2. Further data on use pattern and residues in milk

No gas chromatographic data were available; however, the results
shown In Table 1 were obtained using the indicated methods.

3. Data on residues in the non-fatty portion of meat and meat
products

Data were available from supervised trials which indicated the
distribution of crufomate in body tissues of cattle and sheep
after various applications. These are summarized in Table 2.

TABLE 1 Residues in milk following application of crufomate to dairy cattle

No. of Application¹ Post-
animals type rate treatment Residues in Sensitivity (ppm)
(mg/kg) interval milk (ppm) and method²

1 Topical- 50 12 h 0.18 0.02
pour-on 2 days 0.09 (Flyhead CLE
2 days 0.03 inhibition)
3-8 days <0.02

1 pour-on 37 12 h 0.24 "
1 day 0.08
2-4 days <0.02

1 52.4 6 h 0.100 0.025
22 h 0.042 (P determination)
28 h 0.028
46 h 0.024

1 49.2 6 h 0.170 "
12 h 0.024
28 h 0.026
46 h 0.014

1 pour-on 65.9 6 h 0.195 0.025
22 h 0.053 (P determination)
28 h 0.066
46 h 0.057

3 " 55.6 12 h 0.100-0.195 0.02
1 day 0.020-0.042 (P determination)
2 days 0.014-0.057

1 Oral 37.5 1 day 0.14 0.02
(drench) 2 days <0.02 (Flyhead ChE
3 days <0.02 inhibition)

1 Intra - 10 12 h 0.08 0.02
peritoneal 1 day 0.05 (Flyhead ChE
2-4 days 0.02 inhibition)

¹ The recommended use pattern included all formulations of
crufomate applied to dry dairy cattleg not to be used on
lactating cattle nor applied within 3 days of freshening.

² Data obtained by coloximetric analysis are omitted because the
sensitivity of the method (0.2 ppm) is not adequate for the
recommended tolerance of 0.05 ppm.

TABLE 2 Residues in animal tissues following application of crufomate

Post-
No. of Application treatment¹ Residues in cattle tissues (ppm)²
animals type rate (mg/kg) interval Fat Muscle Liver Brain
(days)

3 topical- 52-78 7 (R) 0.2-0.7 0.05-0.3
spray (S) 0.3-1.3

3 " 105-156 7 (R) 0.5-0.8 0.2-0.9 0.06-0.2 0.2-0.3
(S) 0.6-1.6

3 " 52-78 7 (R) 0.5-1.6 0.2-0.4

(3 treatments at (S) 0.8-1.4
7 day intervals)

3 topical- 52-78 7 (R) 0.06-0.2 0.05-0.2
spray (S) 0.07-0.2
(different
formulation)

3 spray 104-156 7 (R)<0.05-0.7 0.1-0.2
(S) 0.1 -2.4
3 " 52-78 7 (R)<0.05-0.08 0.05-0.2
(3 treatments at (S) 0.1-0.2
7 day intervals)

3 spray 37.5 7 0.07-0.09 0.03-0.08 <0.02-0.07
(different
formulation)

10 topical- 52 7 (O)<0.02
pour-on

TABLE 2 (Cont'd.)

Post-
No. of Application treatment¹ Residues in cattle tissues (ppm)²
animals type rate (mg/kg) interval Fat Muscle Liver Brain
(days)

3 topical 52 28 (S)<0.05 <0.05 <0.05
pour-on
3 " 104 28 (S) 0.05-0.22 <0.05 <0.05
5 " 52 8 (O) 0.02
5 " 39 7 (O) 0.05-0.15

2 oral 75 14 (R)<0.05 <0.03

1 spray 473 ml. of 14 (O) 0.18 0.025-0.035 0.90 0.15
2% emulsion (analyses by ³²P)

Residues in sheep tissues (ppm)

1 oral 89.8 14 0.002 0.004 0.018
3 oral 200 7 <0.03 <0.05
3 oral 200 7 <0.03 <0.05
(3 doses at 2-week intervals)

1 For all formulations, all treatments, and all animals, the
recommended withdrawal period is 7 days minimum between last
application and slaughter.

2 (R) - renal fat; (S) - subcutaneous fat; (O) - omental fat.

4. Comparative evaluation of gas-liquid chromatographic methods
for regulatory purposes

A gas chromatographic method of analysis for crufomate residues
in animal tissues has been developed (Rice and Dishburger, 1970).
The method employs a phosphorus-sensitive detector and has a
limit of determination of about 0.02 ppm. The extraction and
clean-up procedures employed for various tissues allow for the
nearly equal partitioning of crufomate into fat and aqueous
phases. The method has many features in common with existing
multi-residue methods of analysis for phosphorus containing
pesticides (Abbott et al., 1970; and Storherr et al., 1971).
On the basis of these similarities and taking into account the
chemistry of the compound (methyphosphoramidate) it would appear
reasonable that crufomate would be detected by these existing
multi-residue methods. However, in the absence of collaborative
testing data to verify these assumptions, the preferable
multi-residue methods cannot be recommended at this time. The
more specific method, with appropriate adaptations, is therefore
recommended.

The method of analysis for residues in milk using flame
photometric gas chromatography, which was described in the 1968
evaluation of crufomate (Bowman and Beroza, 1967), would be
suitable for adaptation to regulatory use.

APPRAISAL

The four items of further work or information required by the 1968
Joint Meeting are considered to have been met. Although no data were
available from countries other than U.S.A. and U.K. on the use pattern
and resultant residues, the manufacturers gave assurance that the main
uses are in these two countries. New information was available which
better defined the use patterns and withdrawal periods. No information
was available on residues in milk from treated animals using gas
chromatographic methods of analysis. However, the intent of this
requirement was satisfied by new comparative data on milk residues
obtained by fly-head cholinesterase inhibition methods, colorimetric
methods and phosphorus determination methods which supported the
previously recommended tolerance for milk of 0.05 ppm. Data were
received on residues in the non-fatty portion of meat (muscle, heart,
liver, kidney and brain) which showed that residues were about equally
distributed between these tissues and fat. Therefore, the previously
recommended tolerance on meat should be amended by deleting the
bracketed term "(on fat basis)". A method of analysis of residues in
meat has been developed which, with appropriate adaptations, would be
suitable for regulatory purposes. The method of analysis for residues
in milk using flame photometric gas chromatography, which was
described in the 1968 evaluation of crufomate (FAO/WHO, 1969), is
suitable for adaptation to regulatory use.

RECOMMENDATIONS

TOLERANCES

The temporary tolerances in effect until 1972 are replaced by
tolerances, as amended below:

ppm

Meat 1

Milk (whole) 0.05

FURTHER WORK OR INFORMATION

REQUIRED (If tolerance is to be recommended)

Data on residues in milk products and partition into milk fat.

DESIRABLE

Further information on residues in milk from treated animals using
modern gas chromatographic methods of analysis.

REFERENCES

Abbott, D.C., Crisp, S., Tarrant, K.R. and Tatton, J.O.G. (1970)
Pesticide Residues in the total diet in England and Wales, 1966-1967.
III. Organophosphorus pesticide residues in the total diet, Pest.
Sci., 1: 10-13 (Jan.-Feb., 1970).

Bowman, M.C. and Beroza, M. (1967) Temperature programmed gas
chromatography of twenty phosphorus-containing insecticides on four
different columns and the application to the analysis of milk and corn
silage. J. Ass. off. analyt. Chem., 50: 1228-1236.

Dow Chemical. (1972) Residue data and recommended use patterns for
crufomate in meat and milk (unpublished).

FAO/WHO. (1969) 1968 Evaluations of some pesticide residues in food.
FAO/PL: 1968/M/9/1; WHO/FOOD ADD./69.35.

Rice, J.R. and Dishberger, H.J. (1970) Gas chromatographic
determination of residues of crufomate, 4-tert-butyl-2-chlorophenyl-
methyl methylphosphoromidate, in bovine muscle, liver, fat and blood
tissues. ACR 70.4, 16 February 1970.

Storherr, R.W., Ott, P. and Watts, R.R. (1971) A general method for
organophosphorus pesticide residues. J. Ass. off. analyt. Chem., 54:
513-516.

    See Also:
       Toxicological Abbreviations
       Crufomate (ICSC)
       Crufomate (FAO/PL:1968/M/9/1)