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

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The NOAEL in rats was 1500 ppm, equal to 37 mg/kg bw per day in males and 45 mg/kg bw
per day in females, on the basis of deaths, clinical signs, decreased body-weight gain and effects on
haematological and clinical chemistry parameters at 1500 ppm (Norvell, 1983).
In a short-term study, groups of five male and five female Alpk:APfSD (Wistar-derived)
rats were exposed (nose-only) to cypermethrin technical (purity 87.1%, cis : trans 50.1 : 49.9) at
concentrations of 0, 10, 50 or 250 mg/m 3 for 15 days by inhalation for 21 days. The mass median
aerodynamic diameter (MMAD) of the aerosol particles in the chamber was 2.6–2.9 μm, with a
geometric standard deviation (GSD) of 1.8–2.1 μm. Satellite groups of five males and five females
from rats in the control groups and from those receiving the highest dose were retained for 14 days
after the exposure period. Concentrations of cypermethrin were determined in the brains of additional
control and highest-dose interim-sacrifice groups (five of each sex, killed on day 10) and an additional
five of each sex for all doses, killed on day 22. Rats were monitored daily for clinical signs, and
detailed clinical examinations and body-weight measurements were made on days 1, 2, 3, 8, 15 and
22, and weekly thereafter for the satellite groups. Food consumption was calculated on a weekly basis.
At termination, haematology and clinical chemistry parameters were determined for all animals in
the main study and satellite groups, a full postmortem was conducted, and selected organs weighed.
Histopathology was restricted to the control group and group at 250 mg/m 3 groups, plus lungs and
abnormal tissues from the other groups.
There were no deaths. Immediately after exposure, salivation and lachrimation were observed
in rats in the group at 250 mg/m 3 , together with decreased activity and tail erection in both sexes,
and head/paw flicking, reduced stability and tiptoe gait in females. At 50 mg/m 3 , there were sporadic
observations of salivation that were probably related to exposure to the test substance. As no other
signs were present at this dose, the study author did not regard this as toxicologically relevant.
However, given that the highest dose produced salivation and this was not noted in controls, the
salivation findings at 50 mg/m 3 should not be dismissed. On non-exposure days, piloerection or
ungroomed appearance were noted for some animals exposed at 250 mg/m 3 . Slight body-weight
loss (< 5%) was observed at 250 mg/m 3 on day 2 in both sexes, and while female body weight
recovered after cessation of treatment, male body weights remained below controls (6–8%) for the
remainder of the treatment and recovery periods. Food consumption was reduced at 250 mg/m 3 in
the first week of treatment (12–15%), but was subsequently similar to controls. Relative to controls,
slight (5–7%) but statistically significant reductions in haemoglobin, erythrocyte volume fraction and
erythrocyte counts were seen in males and females at 250 mg/m 3 , and occasionally at lower doses, but
as these changes were small and dose–response relationships were lacking, they were not attributed to
treatment. Similarly, there were slight (5–6%) but statistically significant decreases in total protein in
males at ≥ 50 mg/m 3 , and in females at 250 mg/m 3 , the latter accompanied by a decrease in albumin of
a similar magnitude. However, a dose–response relationship was not present in males, and taking into
account the small differences from control values, these findings were not considered toxicologically
significant. Decreases in alanine aminotransferase activity in males at ≥ 50 mg/m 3 (approximately
25%) also lacked a dose–response relationship and were not supported by changes in other liver
enzymes or histopathology. Differences in organ weights between control and treated groups that
attained statistical significance were generally small (< 10%), lacked dose–response relationships, or
were not significant when expressed as a percentage of body weight, and therefore were not attributed
to treatment. In addition, other than the observation of red lungs in one male exposed to cypermethrin
at 250 mg/m 3 , and for which no histopathology was reported, there were no findings at macroscopic
or microscopic examination that indicated treatment-related effects. Cypermethrin was detected in
the brain of one treated animal killed at day 10 (65 ng/g tissue), but concentrations were below the
limit of detection in all other animals. The no-observed-adverse-effect concentration (NOAEC) was
10 mg/m 3 for males and females on the basis of clinical signs of salivation at 50 mg/m 3 (0.05 mg/l)
(Parr-Dobrzanski, 1994).
CYPERMETHRINS X-X JMPR 2006