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EC number: 420-380-5
CAS number: 136465-81-1
A 28-day repeated oral administration study of subacute toxicity in the
rat was conducted with PTH-decahydroamide. The main study dose levels
were set using data from 5-day preliminary toxicity investigation.
Range-finding results indicated suitable dose levels were 0, 30, 150 and
600 mg/kg bw/day. The study design was based on the test guidelines set
out in EEC Directive 92/69/EEC, B.7 subacute toxicity - oral, 1992 and
OECD Test Method No. 407, Repeated Dose Oral Toxicity - Rodent, 1981.
PTH-Decaydroamide was administered daily by oral gavge to groups of five
male and five female Wistar rats. The test guideline parameters -
clinical signs, bodyweights, food consumption, ophthalmoscopy, clinical
pathology, haematology, organ weights, terminal necropsy and subsequent
histopathology were completed in accordance with the test methods.
Formulations of PTH-decahydroamide were confirmed by analysis to be
accurate, stable and homogeneous.
There were no teatment-related findings of any toxicological
significance in the animals dosed at 30 or 150 mg/kg bw/day.
In the 600 mg/kg bw/day group, five of the rats died (on treatment days
6, 7 or 14) and the remaining five were humanely terminated on welfare
grounds on Day 18. The marked signs of toxicity, observed ante-mortem,
included clinical signs of convulsive movements, abnormal posture,
abnormal gait, recumbency and laboured respiration. Decreased red blood
cell counts and reduced haemoglobin content were recorded in the males
and females; decreased mean corpuscular haemoglobin concentration and an
increased mean corpuscular volume were noted among the males only. Total
protein and albumin levels were reduced for males and females and the
inorganic phosphate levels were increased in both sexes. Increased liver
enzyme activities were recorded for one male rat. Necropsy of the high
dose rats revealed vacuolation or centrilobular necrosis in the liver of
four males and one female.
Based on the results of the repeated administration of
PTH-decahydroamide at 30, 150 or 600 mg/kg bw/day, the no observed
effect level (NOEL) was 150 mg/kg bw/day and the LOAEL was 600 mg/kg
The marked effects observed at 600 mg/kg bw/day including mortality,
functional disturbances and toxicologically significant effects (e.g.
convulsions) indicate consideration of the risk phrase R48 "Danger of
serious damage to health by prolonged exposure". However, this is only
appropriate where effects are observed in rats following oral
administration at 50 mg/kg bw/day in a repeated administration study or
at levels circa three-fold higher in a subacute study. Since the effects
were not apparent at 150 mg/kg bw/day and only observed at the next
higher dose level, classification as R48 or STOT-RE Cat 1 or 2 is not
considered appropriate for PTH-decahydroamide.
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