Pesticide residues in food — 2006: Toxicological ... - ipcs inchem

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Haloxyfop (racemic), its sodium salt and its esters (racemic haloxyfop ethoxyethyl ester
and racemic haloxyfop methyl ester) were first evaluated by the JMPR in 1995, when the Meeting
established an acceptable daily intake (ADI) of 0–0.0003 mg/kg bw based on a no-observed-adverseeffect
level (NOAEL) of 0.03 mg/kg bw per day for liver tumours in a 2-year study in mice. New
toxicological data had been made available since this date. Haloxyfop was re-evaluated at the request
of the Codex Committee on Pesticide residues (CCPR). New data on pharmacokinetics, dermal
toxicity, genotoxicity and special studies of hepatocellular peroxisome proliferation had become
available since the last evaluation.
All studies with haloxyfop-R methyl ester and pivotal studies with haloxyfop were certified
as being compliant with good laboratory practice (GLP). Other studies were carried out before
the Organisation for Economic Co-operation and Development (OECD) guidelines on GLP were
promulgated. The quality of these studies was considered to be acceptable.
Numerous studies of the pharmacology and toxicology of various chemical forms of haloxyfop
were available. Investigations with haloxyfop-R and its methyl ester were limited to studies of
absorption, distribution, metabolism and excretion, acute toxicity, short-term studies of toxicity, and
genotoxicity.
Haloxyfop-R methyl ester and haloxyfop-R are used as active ingredients in herbicide
products used on crops, including carrots, fodder legumes, rapeseed, soya bean and sugar beet.
The R-isomer is the herbicidally-active form of the chemical. Haloxyfop-R methyl ester and
haloxyfop-R are the only forms of haloxyfop that are now manufactured and registered globally,
although racemic forms and the ethoxyethyl ester have been used in the past. Commercially
produced haloxyfop-R methyl ester contains a minimum of 98% of R-isomer and a maximum of
2% S-enantiomer.
The CAS Nos for these substances are: haloxyfop methyl ester, 69806-40-2; haloxyfop-R methyl
ester, 072619-32-0; haloxyfop acid, 69806-34-4; and haloxyfop ethoxyethyl ester (haloxyfop-etotyl),
87237-48-7. The structural formula of haloxyfop acid is shown in Figure 1.
Chemical names (IUPAC) for these substances are as follows: racemic haloxyfop acid:
(RS)-2-[4-[3-chloro-5-trifluoromethyl-2-pyriyloxy)phenoxy]propionic acid; haloxyfop-R methyl ester,
methyl (R)-2-[4-[3-chloro-5-trifluoromethyl-2-pyriyloxy)phenoxy]propionate; racemic haloxyfop
ethoxyethyl ester, ethoxyethyl (RS)-2-[4-[3-chloro-5-trifluoromethyl-2-pyriyloxy)phenoxy]propionate.
Figure 1. Structural formula of haloxyfop acid
O
F 3 C
N
O
OH
O
Cl
HALOXYFOP X-X JMPR 2006