Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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2.4 Genotoxicity
Aminopyralid (batch No. F0031-143, TSN102319) and aminopyralid TIPA (batch No. 173-
162-1A, TSN104110) were tested for genotoxicity in assays for reverse mutation in S. typhimurium
and E. coli, an assay for HGPRT forward mutation in Chinese hamster ovary cells (CHO), an assay
for chromosomal aberration in rat lymphocytes in vitro and an assay for micronucleus formation in
mouse bone marrow in vivo. All four studies complied with GLP.
The results of all assays except that for chromosomal aberration in rat lymphocytes were clearly
negative ( Table 14). Chromosomal aberrations were only found after 24 h of treatment (but not
after 4 h) in the absence of metabolic activation (S9) at concentrations that clearly reduced mitotic
indices, indicative of a cytotoxic potential for aminopyralid (Table 15).
Table 14. Results of studies of genotoxicity with aminopyralid and aminopyralid TIPA
Test article End-point Test object Concentration Purity (%) Result Reference
In vitro
Aminopyralid
Reverse
mutation
Salmonella
typhimurium
TA98, TA100,
TA1535,
TA1537 and E.
coli WP2uvrA
100–5000 μg/plate
± S9, in DMSO
94.5 Negative Mecchi
(2001)
Aminopyralid
TIPA
Reverse
mutation
S. typhimurium
TA98, TA100,
TA1535,
TA1537 and E.
coli WP2uvrA
33.3–5000 μg/plate
(7.3–1090 μg/plate
aminopyralid equivalents)
in DMSO ± S9,
in DMSO
21.8%
aminopyralid
equivalents
Negative
Charles
& Mecchi
(2004)
Aminopyralid
Forward
mutation
Hgprt locus in
CHO cells
31.25–2070 μg/ml ±
S9, in DMSO
94.5 Negative Linscombe
et al. (2001)
Aminopyralid
TIPA
Forward
mutation
Hgprt locus in
CHO cells
250–4000 μg/ml
(54.5–872 μg/ml
aminopyralid
equivalents) ± S9,
in DMSO
21.8%
aminopyralid
equivalents
Negative
Schisler
et al. (2004)
Aminopyralid
Chromosomal
aberrations
Rat
l ymphocytes
32.3–2070 μg/ml ± S9,
in DMSO
94.5 Negative +S9
Positive −S9
(see Table 15)
Linscombe
et al. (2002)
Aminopyralid
TIPA
Chromosomal
aberrations
Rat
l ymphocytes
1000–4000 μg/ml
(218–872 μg/ml
aminopyralid
equivalents) ± S9,
in DMSO
21.8%
aminopyralid
equivalents
Negative
Linscombe
et al. (2004)
In vivo
Aminopyralid
Micronucleus
formation
Male CD-1
mice
2 × 500–2000 mg/kg
bw on two c onsecutive
days
94.5 Negative Spencer
& Gorski
(2002)
Aminopyralid
TIPA
Micronucleus
formation
Male CD-1
mice
2 × 500–2000
(109–436
aminopyralid equivalents)
mg/kg bw on
two consecutive days
21.8%
aminopyralid
equivalents
Negative
Spencer
et al. (2004)
CHO, Chinese hamster ovary cells; S9, 9000 × g supernatant from rat livers; TIPA, triisopropylammonium
AMINOPYRALID 3–36 JMPR 2007