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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets scientific standards with acceptable restrictions (only 5 rats per dose, restricted to survival and body weight gain; histopathology of selected organs; no analytical control of dose level; no data on clinical signs).

Data source

Reference
Reference Type:
publication
Title:
Toxicological studies of compounds investigated for use as inhibitors of biological processes. Toxicity of Ethylene Chiorohydrin
Author:
Ambrose AM
Year:
1950
Bibliographic source:
Arch Ind Hyg Occup Med 2: 591-598

Materials and methods

Principles of method if other than guideline:
Toxic effects in young rats exposed via the diet for 220-403 days
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No details

Test animals

Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
no details except: weanling male rats, mean weight at initiation 47 g

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Details on oral exposure:
no details
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
220 days (1.28, 0.64, 0.32, 0.24; 0.16; 0.08; 0.04; 0.02; 0.01 % in the diet);
403 days (0.12% in the diet)
Frequency of treatment:
continuously, ad libitum
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 0.01; 0.02; 0.04; 0.08; 0.12; 0.16; 0.24; 0.32; 0.64; 1.28 % in the diet
Basis:

Remarks:
Doses / Concentrations:
0, 5-10, 10-20, 20-40, 40-80, 60-120, 80-160, 120-240, 160-320, 320-640, 640-1280 mg/kg bw/day
Basis:
other: corresponding dose range (old-young rat) for each dose level
No. of animals per sex per dose:
5 males
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: no data
Positive control:
no

Examinations

Observations and examinations performed and frequency:
Food consumption and body weight measured weekly; data on mortality given
Sacrifice and pathology:
Necropsy of all surviving rats (not done in animals which died during the exposure period).
Histopathology of selected organs: heart, lung, liver, spleen, kidney, adrenal, pancreas, stomach, intestine, urinary bladder, testis and thyroid.
Other examinations:
no
Statistics:
no details; means and standard error of means (SE) calculated

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Mortality
rats receiving a diets containing 0.32, 0 .64 and 1.28 % test substance were concluded within 49, 16 and 7 days, respectively, by death of animals. 2/5 rats died during the exposure period at 0.24% (no further details).

Body weight
at >=0.16% body weight clearly lower than in control group (difference >10%); growth curves lower but nearly parallel to control
at 0.12% slight but statistically significant decrease in body weight gain during the 1st 200 days; at day 403 the average weight was 311 g which was slightly below the control value at day 220 (no concurrent control).

Food consumption
at >= 0.16% reduced food consumption; at 0.16% slight reduction but not significant.

Histopathology
No effects detected (" results were essentially negative").

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
0.08 other: % in the diet
Sex:
male
Basis for effect level:
other: body weight
Dose descriptor:
NOEL
Effect level:
40 - 80 mg/kg bw/day (nominal)
Sex:
male

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In male rats receiving the test substance via the diet no effects were found at a dose level of 0.08% or 40-80 mg/kg bw/day (restricted parameters).
Executive summary:

Study meets scientific standards with acceptable restrictions (only 5 rats per dose, restricted to survival, body weight gain and histopathology of selected organs; no analytical control of dose level; no data on clinical signs).

In a feeding study 5 male rats per dose level were exposed to 0, 0.01; 0.02, 0.04, 0.08, 0.12, 0.16, 0.24, 0.32, 0.64, 1.28 % in the diet for 220 days. One dose group (0.12%) was exposed for 403 days. These dose levels in the diet correspond to 0, 5-10, 10-20, 20-40, 40-80, 60-120, 80-160, 120-240, 160-320, 320-640, 640-1280 mg/kg bw/day. All rats died at doses >= 0.32% and 2/5 at 0.24%. Effects on body weight were found at >= 0.12%. At >= 0.16% a reduced food consumption was recorded; at 0.16% there was only a slight but not significant effect. Histopathological examination of survivors revealed no treatment related effects.

Conclusion: In male rats receiving the test substance via the diet no effects were found at a dose level of 0.08% or 40-80 mg/kg bw/day (restricted parameters).