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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
sub-chronic toxicity: other route
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study meets scientific standards with acceptable restrictions (partly limited documentation).

Data source

Reference
Reference Type:
publication
Title:
Toxicity of ethylene chlorohydrin II: subacute toxicity and special tests
Author:
Lawrence WH, Itoh K, Turner JE, and Autian J
Year:
1971
Bibliographic source:
J Pharmacol Sci 60: 1163-1168

Materials and methods

Principles of method if other than guideline:
Toxic effects in rats after thrice weekly i.p. injection for 3 months
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity > 99%
Source: Matheson, Coleman, and Bell, East Rutherford, N. J.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
12 weeks
Frequency of treatment:
Thrice weekly (Mo, We, Fr)
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 6.4, 12.8, 32 mg/kg bw/injection; concentrations/application volume not given
No. of animals per sex per dose:
12 male rats per dose; at 0 and 12.8 mg/kg bw totally 24 animals (experiment repeated)
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: keine Angaben

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
12.8 other: mg/kg bw/injection
Sex:
male
Basis for effect level:
other: overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Survival

in the 1st trial 4/12 rats died at 12.8 mg/kg bw; authors presumed an overdose and repeated the experiment; no mortality was found at this dose level. At 32 mg/kg bw 6/12 rats died. No mortality occurred at 6.4 mg/kg bw.

Body weight gain, food consumption, hematology, pathology: no significant treatment related effects.

Applicant's summary and conclusion

Conclusions:
No adverse effects were detected in male rats after thrice weekly i.p. injection for 12 weeks at a dose level of 12.8 mg/kg bw/injection, the LOAEL was 32 mg/kg bw/injection.
Executive summary:

The study meets scientific standards with acceptable restrictions (partly limited documentation).

In a subchronic study 12 -24 male Sprague-Dawley rats per group received thrice weekly i.p. injections of 0, 6.4, 12.8, 32 mg/kg bw/injection for 12 weeks. Clinical signs, food consumption, body weight, hematology, necropsy data, organ weights were recorded and histopathology of selected organs performed. Survival was reduced at 32 mg/kg bw. No further treatment related effects were detected.

Conclusion: No adverse effects were detected in male rats after thrice weekly i.p. injection for 12 weeks at a dose level of 12.8 mg/kg bw/injection, the LOAEL was 32 mg/kg bw/injection.