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

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change was considered to be a physiological adaptation and not of toxicological significance. There
were no other treatment-related findings in either the parameters for general health or reproductive
performance.
The NOAELs for general toxicity and for reproductive toxicity were both 1000 mg/kg bw per
day, the highest dose tested (Marty et al., 2003).
(b)
Developmental toxicity
Rat
Groups of 25 time-mated female CD rats received aminopyralid (purity, 94.5%; batch No.
F-0031-143, TSN102319) at a dose of 0, 100, 300, or 1000 mg/kg bw per day as a suspension in
0.5% aqueous Methocel (A4M® methylcellulose) in a volume of 4 ml/kg, by oral gavage, starting on
day 6 of gestation and continiuning until day 20. Clinical examinations were conducted throughout
the study, and body weights and feed consumption were recorded regularly. On day 21, dams were
terminated and the fetuses delivered by caesarian section. The weights of gravid uteri, the numbers
of corpora lutea, implantation sites, viable fetuses and resorptions were recorded. Fetuses were sexed
and body weights measured and they were subjected to external, visceral, craniofacial and skeletal
examinations. The study complied with GLP.
In all the parameters examined in this study, no treatment-related findings were found. Under
the conditions of this study, aminopyralid did not show evidence of any maternal or embryo/fetal
toxicity or teratogenicity.
The NOAEL was 1000 mg/kg bw per day, the highest dose tested (Carney & Tornesi, 2001).
Groups of 25 time-mated female CD rats received GF-871 (41.3% aminopyralid TIPA) at a
dose of 0, 484, 1211 or 2421 mg/kg bw per day in a volume of 4 ml/kg, by oral gavage, starting on
day 6 of gestation and continuing until day 19. This dosing regime provided aminopyralid at a dose
of 0, 105, 263 or 525 mg/kg bw per day. Clinical examinations were conducted throughout the study,
and body weights and feed consumption were recorded regularly. On day 21, dams were terminated
and the fetuses delivered by caesarian section. The weights of gravid uteri, the numbers of corpora
lutea, implantation sites, viable fetuses and resorptions were recorded. Fetuses were sexed and body
weights measured and they were subjected to external, visceral, craniofacial and skeletal examinations.
The study complied with GLP.
No treatment-related effects on dams or fetuses were observed even at the highest dose t ested.
The NOAEL for GF-871 was 2421 mg/kg bw per day, or 525 mg/kg bw per day as a minopyralid
equivalents, the highest dose tested (Zablotny & Thorsrud, 2004).
Rabbit
Groups of 26 time-mated female NZW rabbits received aminopyralid (purity, 94.5%; batch No.
F-0031-143, TSN102319) at a dose of 0, 25, 100, or 250 mg/kg bw per day by oral gavage suspensions
in 0.5% aqueous Methocel (A4M® methylcellulose) in a volume of 4 ml/kg, starting on day 7
of gestation and continuing until day 27 (phase I). Since there was no evidence of maternal toxicity
at the highest dose, in a second part of this study with the same design, mated rabbits were given
aminopyralid in suspension at a dose of 0, 500, or 750 mg/kg bw per day (phase II). On day 28, dams
were terminated and the fetuses were delivered by caesarian section. The weights of gravid uteri, the
numbers of corpora lutea, implantation sites, viable fetuses and resorptions were recorded. Fetuses
were sexed and body weights measured and they were subjected to external, visceral, craniofacial and
skeletal examinations. The study complied with GLP.
Mean body-weight gain was significantly reduced at 500 and 750 mg/kg bw per day (−11.8 g
and −70.0 g vs 25 g in the rabbits in the control group) on days 7−10 of gestation. Thereafter, the
reduced body-weight gain remained significant for rabbits at the highest dose only. Intermittently
AMINOPYRALID 3–36 JMPR 2007