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

Endpoint summary

Description of key information

The acute oral LD50 toxicity of 4-Hydroxy-TEMPO was tested in a standard OECD 401 guideline study. Classification: H302, Harmful if swallowed. An LD50 of 1053 mg/kg bw was determined. The acute dermal LD50 toxicity of 4-Hydroxy-TEMPO was tested in a standard OECD 402 guideline study. A limit test with rats at 2000 mg/kg bw dose was performed. A LD50 of >2000 mg/kg was determined. Thus, no classification in regard of dermal toxicity is necessary.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 053 mg/kg bw

Based on:

test mat.

95% CL:

834 - 1 375

Sex:

male

Dose descriptor:

LD50

Effect level:

953 mg/kg bw

Based on:

test mat.

95% CL:

574 - 1 451

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 053 mg/kg bw

Quality of whole database:

Study according to guideline

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline conform study

Additional information

Oral:

In an acute oral toxicity study (83-0232 -FGT), rats (5/sex) were given a single oral dose of 4-Hydroxy-TEMPO in distilled water at doses of 0, 500, 1000, 2000 or 5000 mg / kg bw. Animals were then observed for 14 days. The following treatment related clinical signs were noted: Dyspnoea, exophthalmus, ruffled fur and curved body position. In addition: Ventral and lateral body position, tonic-clonic convulsions and sedation (in all dose groups: dyspnoea and convulsions, the latter for up to 5 hrs past dose, incl. non-moribund animals). Oral LD50 combined: 1053 mg/kg bw (males: 953, females 1155 mg/kg bw).The study was QA-monitored (GLP was not compulsory in 1983) and it satisfies the requirements of OECD test guideline 401. The study is considered acceptable (key study).

Justification for selection of acute toxicity – oral endpoint
Adequate assay to address endpoint

Justification for selection of acute toxicity – dermal endpoint
Only one GLP and guideline study available.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study, the test substance should be classified as Xn, R22 (Harmful, Harmful if swallowed) according to the criteria of EU Directive 67/548/EEC and as Cat. 4, H302 (Harmful if swallowed) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.

Based on the results obtained from acute dermal toxicity study, the substance was not classified and labeled in respect to dermal toxicity according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).