Registration Dossier

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
12 May 1981
Deviations:
no
GLP compliance:
no
Remarks:
but under QA-surveillance
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
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:
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).
Body weight:
500 mg/kg bw: males and females gaining weight until d 14
1000 mg/kg bw: mean body weight of surviving males (n = 2) not recorded; females (n=4) gaining weight until d 14
2000 mg/kg bw: males and females not surviving day 1 (except day 0, no bw data available)
5000 mg/kg bw: males and females not surviving day 0 (except day 0, no bw data available)
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
Remarks:
Migrated information
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.