1,4-dihydroxy-2,2,6,6-tetramethyl piperidinium-2-hydroxy-1,2,3-propanetricarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-01-26 to 1999-03-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant Guideline study.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Reference 2

Reference Type:

other: Amendment Final Report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-370-5

EC Name:

-

Cas Number:

220410-74-2

Molecular formula:

C34H67N3O13

IUPAC Name:

tris(1,4-dihydroxy-2,2,6,6-tetramethylpiperidin-1-ium) 2-hydroxypropane-1,2,3-tricarboxylate

Test material form:

other: Ivory-peach flakes

Details on test material:

- Identification: TKA 45021
- Appearance: Ivory-peach flakes
- Lot/batch No.: pax 2068 rd 100
- Test Item arrived at Test Facility: 1998-11-25
- Storage conditions: desiccated at room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc. (facility not specified), USA
- Age at study initiation: approximately seven to ten weeks
- Weight at study initiation: ranging from 238 to 300 g for males and 214 to 232 g for females
- Fasting period before study: yes
- Housing: individually in suspended stainless steel cages
- Diet: PMI Certified Rodent Chow #5002 (Purina Mills, Inc.), ad libitum
- Water: municipal tap water treated by reverse osmosis, ad libitum
- Acclimation period: minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature: 21°C to 24°C
- Humidity: 35-51%
- Air changes: 10 to 15 air changes per hour
- Photoperiod: 12-hour light / 12-hour dark cycle

IN-LIFE DATES: From: 1999-01-26 To: 1999-03-01

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: deionized water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg / mL (fixed)

MAXIMUM DOSE VOLUME APPLIED:
- males: 6.41 mL / kg bw
- females: 4.272 mL / kg bw

Doses:

males: 1068, 2136, 2670 or 3204 mg / kg bw
females: 534, 1068, 1602 or 2136 mg / kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical abnormalities were recorded approximately 1, 2, 4, 8 and 24 hours post-dose and daily thereafter (days 2-14).
A general health/mortality check was performed twice daily (in the morning and in the afternoon).
Individual body weights were obtained prior to fasting (day -1), prior to dosing on day 0 and for all surviving animals on days 7 and 14.
Animals found dead after day 0 were also weighed.
Individual food consumption was recorded for all surviving animals weekly.
- Necropsy of survivors performed: yes

Statistics:

The LD50 and 95% confidence intervals were calculated separately for males and the combined sexes using a computer adaption of the method of Litchfield and Wilcoxon.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 494.9 mg/kg bw

Based on:

test mat.

95% CL:

1 828.9 - 3 384.8

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 068 - < 1 602 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 757.8 mg/kg bw

Based on:

test mat.

95% CL:

872.6 - 3 541.1

Mortality:

All mortality occurred by study day 1:
males (mg / kg bw : fatalities / totals): 1068 : 0/5, 2136 : 1/5, 2670 : 4/5 or 3204 : 5/5
females (mg / kg bw : fatalities / totals): 534 : 0/5, 1068 : 0/5, 1602 : 5/5 or 2136 : 5/5

Clinical signs:

other: The most notable clinical abnormalities observed during the study included decreased activity, convulsions, wobbly gait, breathing abnormalities, prostration, decreased defecation, soft stools, piloerection, apparent hypothennia, skin blue in color, hunch

Gross pathology:

The most notable gross internal findings were observed in the animals that died and included abnormal content in the digestive tract, stained mucosa in the stomach and dark red lungs. Gross intemal findings observed at necropsy on study day 14 included three incidences of gray raised area(s) on the lungs in the 2136 mg/kg bw male rats.

Other findings:

Food consumption was consistent throughout the test period.