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EC number: 420-380-5
CAS number: 136465-81-1
A NOEL of 150 mg/kg bw/d is identified in a 28-day rat study based on mortality, signs of toxicity, changes in haematological and clinical chemistry parameters and liver pathology at the highest dose level of 600 mg/kg bw/d.
A 28-day repeated oral administration study of sub-acute 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/d. 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 gavage to groups of
five male and five female Wistar rats for four weeks. Various parameters
- clinical signs, bodyweights, food consumption, ophthalmoscopy,
clinical pathology, haematology, organ weights, terminal necropsy and
subsequent histopathology - were investigated in accordance with the
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/d.
In the 600 mg/kg bw/d group, five of the rats died (on treatment days 6,
7 or 14) and the remaining five were 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/d, the no observed effect
level (NOEL) was 150 mg/kg bw/d.
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 is not considered appropriate
Translation of the DSD classification to Regulation 1272/2000 (GHS)
classification can be applied directly to R48/X decisions and
consequently no classification for STOT-RE is required.
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