(1-λ1-oxidanyl-2,2,6,6-tetramethylpiperidin-4-yl) benzoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983-07-29 to 1983-11-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl

EC Number:

218-760-9

EC Name:

4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl

Cas Number:

2226-96-2

Molecular formula:

C9H18NO2

IUPAC Name:

2,2,6,6-tetramethylpiperidine-1,4-diol

Test material form:

solid: flakes

Test animals

Species:

rat

Strain:

other: Tif:RAIf(SPF); F3 crosses of RII1/Tif x RII 2/Tif

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Ltd. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 166 - 226 g
- Fasting period before study: yes, overnight prior to dosing
- Housing: in groups of 5 in Macrolon cages type IV
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ±3°C
- Humidity: 55 ±15%
- Air changes: 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 20. Sept. 1983 To: 06. Oct. 1983

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

(distilled)

Details on oral exposure:

VEHICLE
- Purity: distilled water

MAXIMUM DOSE VOLUME APPLIED: 20 mL / kg body weight

Doses:

5000 and 2000 mg/kg bw (Sep. 20, 1983)
1000 and 500 mg/kg bw (Sep. 22, 1983)

No. of animals per sex per dose:

5 male and 5 female (total: 40 rats)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days or until all symptoms have disappeared, whichever lasts longer
- Frequency of observations: twice daily on workdays (a.m. and p.m.); once daily on weekends (a.m.)
- Frequency of weighing: on days 1, 7, 14 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, daily

Statistics:

Body weight: group means & standard deviations
LD50 and the 95% confidence limit: Logit method (J. Berkson, J. Am. Stat. Ass., 39. 357-65, 1944)

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 053 mg/kg bw

Based on:

test mat.

95% CL:

834 - 1 375

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

953 mg/kg bw

Based on:

test mat.

95% CL:

574 - 1 451

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1 155 mg/kg bw

Based on:

test mat.

95% CL:

784 - 2 194

Mortality:

500 mg/kg bw: 0 (males); 0 (females)
1000 mg/kg bw: 2 within 2 h and 1 on day 1 (males); 1 within 2 h (females)
2000 mg/kg bw: 3 within 1 h and 2 within 2 h (males); 3 within 1 h, 1 within 2 h and 1 on day 1 (females)
5000 mg/kg bw: 5 within 1h (males); 5 within 1h (females)

Surviving animals recovered within 9 days.

Clinical signs:

other: Dyspnoea, exophthalmus, ruffled fur and curved body position. In addition: Ventral and lateral body position, tonic-clonic convulsions and sedation (in all dose groups: dyspnea and convulsions, the latter for up to 5h past dose, incl. non-moribund animals

Gross pathology:

No findings, some isolated cases of spotted edematous lungs.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 toxicity of 4-Hydroxy TEMPO was tested in a standard OECD 401 guideline study. An LD50 of 1053 mg/kg bw was determined.