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Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study obtained through inquiry process. SNIF file obtained from ECHA.

Data source

Reference
Reference Type:
other: SNIF
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
A mixture of: 2,2,6,6-tetramethylpiperidin-4-yl-hexadecanoate; 2,2,6,6-tetramethylpiperidin-4-yl-octadecanoate
EC Number:
415-430-8
EC Name:
A mixture of: 2,2,6,6-tetramethylpiperidin-4-yl-hexadecanoate; 2,2,6,6-tetramethylpiperidin-4-yl-octadecanoate
Cas Number:
86403-32-9
Molecular formula:
C25H49NO2 and C27H53NO2
IUPAC Name:
Reaction mass of 2,2,6,6-tetramethylpiperidin-4-yl hexadecanoate and 2,2,6,6-tetramethylpiperidin-4-yl octadecanoate

Test animals

Species:
other: rat, Wistar (Han: WIST)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
Method of administration:
gavage
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
40 mg/kg bw/d
Basis:
actual ingested
Remarks:
Doses / Concentrations:
200 mg/kg bw/d
Basis:
actual ingested
Remarks:
Doses / Concentrations:
1000 mg/kg bw/d
Basis:
actual ingested
No. of animals per sex per dose:
Male: 10 animals at 0 mg/kg bw/day, 5 animals at 40 mg/kg bw/day, 5 animals at 200 mg/kg bw/day, 10 animals at 1000 mg/kg bw/day .
Female: 10 animals at 0 mg/kg bw/day, 5 animals at 40 mg/kg bw/day, 5 animals at 200 mg/kg bw/day, 10 animals at 1000 mg/kg bw/day
Control animals:
yes, concurrent vehicle
Details on study design:
Standard design with three dose groups. A two-week recovery group was added.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Salivation increased among mid and high dose animals. Some high dose animals displayed some decreases in reflex response.
Mortality:
mortality observed, treatment-related
Description (incidence):
Salivation increased among mid and high dose animals. Some high dose animals displayed some decreases in reflex response.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
High dose males showed decreased body weight
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
In the high dose, males demonstrated a decrease in food consumption during the entire 28 day dosing period, and females showed decreased food consumption during the first two weeks.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Mid and high dose females displayed an increase in thrombocytes. In all males, and in females of the high dose group, prothrombin time was increased.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
In high dose females, glucose and triglyceride values were elevated. Males and females showed reduced blood protein levels. High dose males showed increased ALAT levels.
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Stomach and duodenum showed effects of oral exposure: white areas and redness of the stomach lining, and swelling of duodenal septum.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
In mid and high dose animals, hyperplasia of the duodenal mucosa was observed. No similar effects were seen in the recovery group.
Histopathological findings: neoplastic:
not examined
Details on results:
Clinical observations: In the intermediate and high dose group, dose-dependent increased salivation was observed.
The animals of the high dose group showed bright feces from the second week and at the end of the treatment, reduced activity, skin turgor and righting reflex. Two females of the high dose group did not show the ear reflex.
The discolouration of the feces was seen in the discovery group till the end of the first week of the recovery period. One male of the low dose group showed a reduced righting reflex at day 15. At the examination on day 26 a reduced righting reflex was observed at one male of the intermediate dose and at two male of the low dose group.
In the males of the high dose group a reduced body weight development was measured at the end of the study. The food consumption of these animals was reduced during the whole application period, in the females of the high dose group a reduced food consumption was observed during the first two weeks of the treatment.
Laboratory findings: Haematology: In the females of the intermediate and high dose group an increase of the number of thrombocytes. A prolongation of the prothrombin time in the males in all dose groups (without relation to the doses) and in females of high and low dose group was observed.
Clinical chemistry: In females of the high dose group the values for glucose and triglycerides were increased and in both sexes the protein values were reduced. In the males of the high dose group increased activities for ALAT was determined.
Effects in organs: On the animal body white areas and redness of the mucosa of the stomach and a swelling of the duodenum septum in all animals of the high dose groups were seen. One animal of the intermedium dose group showed a swollen duodenum too.
Microscopically in the animals of the intermediate and high dose group a hyperplasia of the mucosa in the duodenum was
detected. In the recovery groups no treatment related changes were observed.

Effect levels

Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Local irritation effects in the stomach and duodenum from gavage administration

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
This substance was studied in an OECD guideline study (407) for 28-days of oral gavage exposure at doses of 40, 200 and 1000 mg/kg bw/d in Wistar rats. Primary effects involved local irritation in the stomach and duodenum which resolved during the two-week recovery period, with hyperplasia of the duodenum in mid and high dose groups. The NOAEL is conservatively set at 40 mg/kg bw/d.