2-chloroethanol

Repeated dose toxicity: oral

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

Test material information

Constituent 1

Reference substance name:

2-chloroethanol

EC Number:

203-459-7

EC Name:

2-chloroethanol

Cas Number:

107-07-3

Molecular formula:

C2H5ClO

IUPAC Name:

2-chloroethan-1-ol

Details on test material:

No details

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system 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 / concentrations

Doses / concentrations 1

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:

Doses / concentrations 2

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

1

Dose descriptor:

NOEL

Effect level:

0.08 other: % in the diet

Sex:

male

Basis for effect level:

other: body weight

2

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).