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EC number: 212-161-6
CAS number: 766-09-6
oralRepeated dose (28 days), oral, rat, gavage: NOAEL for local effects (males): 20 mg/kg bw, (females): 80 mg/kg bw, NOAEL for systemic effects (males and females): 80 mg/kg bw, Val. 1 (GLP, OECD Guideline 407, Bayer, T8076401, 2006).inhalativread across (CAS 110-89-4) Repeated dose (28 days), rat, inhalative: NOAEC for systemic effects (males and females): 350 mg/m³, NOAEC for local effects (males and females): 70 mg/m³, Val 1 (GLP, OECD Guideline 412, BASF, 46I0523/89065, 1993).
In a subacute oral
repeated dose study according to GLP and OECD Guideline 407 the test
item, analytical purity: 100 %, was administered daily via gavage in
demineralised water to 5 male and 5 female Wistar rats per dose at dose
levels of 5, 20 and 80 mg/kg bw/day for a period of 4 weeks (Bayer,
T8076401, 2006). Control animals were included in the study.
The animals were
regularly observed and weighed. Food and water intake was determined.
Functional Observational Battery (FOB) as well as Motor and Locomotor
Activity (MA/LMA) tests and clinical laboratory investigations on blood
samples were performed. Organs and tissues were subjected to gross and
histopathological investigations and selected organs were weighed.
The test substance was
stable in the vehicle for the duration of use. Formulations given to the
rats were prepared appropriately.
Survival rate as well
as behaviour, clinical appearance and body weight gain of the rats were
not influenced by the treatment up to 80 mg/kg bw. FOB and MA/LMA tests
did not indicate neurotoxicity up to the highest dose group.
Haematological parameters and parameters of clinical chemistry were not
affected by the test substance and no toxicologically relevant gross
lesions or organ weight differences occurred up to 80 mg/kg bw.
Histopathology revealed that one male of the high dose group exhibited
slight inflammation with keratolysis in the forestomach, which indicates
evidence of a local irritation by the test substance. The subacute
toxicity study in the rat is acceptable (reliability 1) and does satisfy
the guideline requirements for a subacute oral study (OECD 407) in
conditions described the NOAEL (=NOEL) for local effects the test item
is established at 20 mg/kg body weight per day in male and 80 mg/kg body
weight per day in female rats. The NOAEL for systemic effects is > 80
mg/kg body weight per day.
There are no data
available about repeated inhalative exposure. The analogue substance
piperidine acts with the same mode of action as 1-ethypiperidine. Both,
1-ethylpiperidine and piperidine cause severe local effects such as
irritation and corrosion and both are toxic if inhaled after short-term
inhalative subacute repeated dose study of piperidine was used as read
In a 28 -day
inhalation toxicity study, performed according to GLP and to the OECD
test Guideline 412, groups of Wistar-rats/Chbb:TH0M (10/dose/sex) were
exposed to the read across test item (99.4% a.i.) vapour at
concentrations of 5, 20, or 100 ppm (20, 70, and 350 mg/m³,
respectively) for 6 hours/day, 5 days/week (BASF, 1993). Analytical
concentrations were 0, 5 ± 0.45, 20 ± 1.5, 100 ± 9.1 ppm, respectively.
The rats received 20 exposures. A control group of 15 male and 15 female
rats inhaled clean air under similar exposure conditions. To investigate
recovery, animals of additional groups (0, 100 ppm, each 5 animals) were
maintained post exposure for 2 weeks. Whole body exposure was performed.
The atmosphere in the breathing zones of the animals was monitored
approximately every 20 minutes. Clinical signs before, during, and after
exposure were observed daily; body weights were measured at the
beginning of the study and weekly thereafter. Subgroups of five
animals/sex/group were subjected to a battery of neurofunctional tests
before exposure and on days 2, 8, 14, and 28. Clinical pathology of
blood and urine was investigated in subgroups of five rats/sex/group.
Furthermore, ophthalmologic examinations, postmortem, gross pathology,
organ weight measurements, and histopathological examination of selected
tissues was performed.
Only at the highest
concentration of 100 ppm a reddish crust (positive for blood),
indicating upper respiratory tract irritation, was observed as
treatment-related clinical signs on the nasal edges of three male rats
on day 2 of the study, all males from day 3 to the end of the study, two
females on day 3, one female rat on day 4, and almost all females
starting on day 8 increasing to all females by the end of the study.
This finding was not observed in the post-exposure observation period.
At 100 ppm there was a trend (not statistically significant) to body
weight retardation in male subgroups (3.4% and 5.7%) compared to
controls; females did not show a trend toward decreased body weights.
The only notable effects on the neurofunctional battery were increased
hindlimb grip strength in 100 ppm males on day 8 and decreased response
to the hot plate test on day 14 in 5 males of the high dose group. Due
to the transient effects and the no dose-related trend, the effects are
unlikely to be treatment related. No treatment-related effects were
observed on the eyes, haematologic or clinical chemistry parameters,
urinalysis, ophthalmology and pathology. Treatment-related effects were
not observed at 5 or 20 ppm.
The subacute toxicity
study in the rat is acceptable (reliability 1), and does
satisfy the guideline requirement for a subacute inhalative study (OECD
412) in rodents.
No-observed-effect-concentration (NOEC) under the conditions of the test
is 20 ppm (70 mg/m³) for local effects.
In summary, the
NOAEC for systemic effects is 350 mg/m³ body weight, the highest dose
tested and the local NOAEC is 70 mg/m³.
Substance Directive (67/548/EEC)
experimental test data for repeated dose toxicity are reliable and
suitable for the purpose of classification under Directive 67/548/EEC.
As a result the substance is not warranted to be classified for repeated
dose toxicity under Directive 67/548/EEC.
Labeling, and Packaging Regulation (EC) No. 1272/2008
experimental test data for repeated dose toxicity are reliable and
suitable for the purpose of classification under Regulation (EC)
No.1272/2008. As a result the substance is not warranted to be
classified for repeated dose toxicity, under Regulation (EC)
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