Registration Dossier

Toxicological information

Repeated dose toxicity: other routes

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: The study was performed by intravenous route, which is not used for regulatory purpose under REACH, therefore it is not considered relevant, reliable and adequate for classification.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1967
Report date:
1967

Materials and methods

Principles of method if other than guideline:
Hoechst guideline
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-chloroacetamide
EC Number:
201-174-2
EC Name:
2-chloroacetamide
Cas Number:
79-07-2
Molecular formula:
C2H4ClNO
IUPAC Name:
2-chloroacetamide
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Chloracetamid
- Other: Technical substance, supplied by the manufacturing plant (Gersthofen)

Test animals

Species:
rabbit
Strain:
other: Yellow-Silver breed
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: average 1.910 kg (1.570 kg - 2.390 kg)
- Housing: Individual cages
- Diet: Standard-Diät Altromin K by Altromin GmbH Lage/Lippe (Germany) (during study and recovery period)
- Water: Tap water
- Acclimation period: At least 5 days before study

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22-25°C
- Humidity (%): 35-60%
- Air changes (per hr): Partially airconditioned rooms

Administration / exposure

Route of administration:
intravenous
Vehicle:
physiological saline
Details on exposure:
Injection into the ear vein 1x/day i during 30 days
Daily fresh dilutions prepared and produced with physiology. saline solution
Every animal was applied with 1 mL/kg bw (concentrations were adjusted)
Duration of treatment / exposure:
30 days
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 2, 10, 25, 50, 100 mg/kg bw/day,
corresponding to concentrations of 0, 0.2, 1.0, 2.5, 5.0, 10.0 % in physiological saline.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
- Post-exposure recovery period in all survivors: 5 days

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily: behavior

BODY WEIGHT: Yes
- Time schedule for examinations: 3x weekly

HAEMATOLOGY: Yes
- Time schedule for collection of blood: before start and at end of study
- Anaesthetic used for blood collection: No data
- How many animals: all 30 animals
- Parameters examined:
Hemoglobin
Erythrocyte count
Leucocyte count
Heinz bodies

CLINICAL CHEMISTRY: No

URINALYSIS: Yes
- Time schedule for collection of urine: before start and at end of study
- Parameters examined:
Appearance
Color
Protein
Glucose
Sediment

After the study, all surviving animals were observed 5 days
Sacrifice and pathology:
The surviving animals were sacrificed by rabbit-punch and exsanguination. The same procedure was done for animals which had died during the study - except animals of the highest dosage group which had died after the first or second application.
GROSS PATHOLOGY: Yes ,after 3-4 days recovery
- gross assessment:
-relative organ weights (% of bw)

HISTOPATHOLOGY: Yes
- histological assessment of heart, lungs, liver, kidneys, adrenals, ovaries, pancreas, brain, pituitary gland, and thyroid

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Haematological findings:
effects observed, treatment-related
Urinalysis findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Details on results:
Doses 2 / 10 mg/kg bw: over the whole study period, no toxicological observations. Normal weight gains. Hematology and urinanalyis: normal. Macroscopical and histological assessments: no effects.

25 mg/kg bw: paralysis of extremities, animals almost immobile, barely food intake, diarrhea, animals set off urine on touching, normal urinalysis, minor changes in blood count (decreased hemoglobin in 3 survivors). Macroscopical and histological assessments: no effects. 1/5 rabbit died during the study.

50 mg/kg bw: paralysis of extremities, animals almost immobile, barely food intake, diarrhea, animals set off urine on touching. Urinalysis and hematology not possible because all animals died. Macroscopical and histological assessments: no effects. 5/5 rabbits died within half time of the study.

100 mg/kg bw: 5/5 rabbit died within 48 h after the first or second injection.

Effect levels

Dose descriptor:
NOAEL
Effect level:
10 mg/kg bw/day (nominal)
Sex:
female
Basis for effect level:
other: clinical signs; mortality; body weight; clinical chemistry; urinalysis; gross pathology; organ weights; histopathology

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Intravenous application of Chloracetamid in a 30 days repeated dose study caused dose dependent paralysis and death from a dose of 25 mg/kg or higher. At the lower doses (2 and 10 mg/kg bw) no toxic effects were observed. Decreased hemoglobin was seen at a dose of 25 mg/kg .The NOAEL for Chloroacetamide in this study was determined to be 10 mg/kg bw/day.
Executive summary:

In a 30 days repeated dose study, 5 groups and 1 control group of each 5 female rabbits onderwent daily intravenous injection in the ear vein with 1mL/kg bw of Chloroacetamide at different concentrations in order to get doses of 2, 10, 25, 50 and 100 mg/kg bw. On all animals hematology and urinalysis was examined before the start and at the end of the study. Behavior of the animals was observed daily and body weight 3 times weekly. At the end of testing, after 5 days recovery, all survivors were killed and gross pathology and histopathology was performed. All animals that died during the study also underwent gross pathology and histopathology except that no histopathology was done at the high dosed animals that died at first or second application. At doses of 2 and 10 mg/kg bw no toxic effects were observed. Intravenous application of Chloroacetamid caused dose dependent paralysis and death from a dose of 25 mg/kg or higher. Decreased hemoglobin was seen at a dose of 25 mg/kg bw (in the 50 and 100 mg/kg bw dose groups no hematology or urinalysis was possible because all animals died). The NOAEL for Chloroacetamide in this study was determined to be 10 mg/kg bw/day.