Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to OECD Guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Ethane, 2-Chloro-1, 1-Dimethoxy-
IUPAC Name:
Ethane, 2-Chloro-1, 1-Dimethoxy-
Constituent 2
Reference substance name:
97-97-02
IUPAC Name:
97-97-02
Constituent 3
Chemical structure
Reference substance name:
2-chloro-1,1-dimethoxyethane
EC Number:
202-624-0
EC Name:
2-chloro-1,1-dimethoxyethane
Cas Number:
97-97-2
Molecular formula:
C4H9ClO2
IUPAC Name:
2-chloro-1,1-dimethoxyethane
Test material form:
other: colourless liquid
Details on test material:
- Name of test material (as cited in study report): Chloroacetaldehyde dimethylacetal
- Physical state: colourless liquid
- Storage condition of test material: room temperature
- Container: brown glass bottle x2

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (U.K.) Limited, Manston, Kent
- Age at study initiation: 5-6 weeks
- Weight at study initiation: males 188-222g, females 153-184g
- Housing: polypropylene grid-floor cages suspended over trays containing absorbent paper
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): 48-59%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Doses:
50, 250, 500 mg/kg BW
No. of animals per sex per dose:
3/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: day 1, 4, 8, 11 and 14
- Necropsy of survivors performed: yes: All decedents and animals killed on day 15 were subjected to a full macroscopic, internal and external examination
- Other examinations performed: twice daily for 14 days for overt signs of toxicity, ill health or behavioural change
- concentrations: 0, 50, 250, 500 mg/kg/day

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: none
Mortality:
One male treated with 500 mg/kg/day was found dead on day 2, the remaining males were killed in extremis at the end of the working
day. Due to the severe nature of the observations detected in one female the following morning, the animal was killed in extremis.
The remaining two females were also killed in extremis after the 1 hour observations had been performed. One male from the 250 mg/kg/day dose group was found dead on day 3. There were no deaths in the 50 mg/kg/day dose group.
Clinical signs:
no abnormalities in control group and 50mg/kg/day group.
250 mg/kg/day: Lethargy, Ataxia, Death, increased salivation immediatley after dosing, increased salviation, wet fur, red/brown staining around mouth
500 mg/kg/day: increased salivation immediatley after dosing, hunched posture, Lethargy, Pilo-erection, Extreme Lethargy, Decreased respiration rate, Increased salivation, Ataxia, Pallor of the extremities, Chromodacryorrhoea, Dehydration, Death
Body weight:
250 mg/kg/day: slight reduction in body weight gain
50 mg/kg/day: body weight gain was comparable with that seen in controls
Other findings:
Necropsy:
500 mg/kg/day: animal found dead on day 2 showed macroscopic abnormalities consistent with normal post mortem changes. These included dark lungs, liver and kidneys, sloughing of the glandular gastric epithelium and congestion of the small intestine. Further abnormalities detected in the animals killed in extremis included pale spleen, pale kidneys, pallor or patchy pallor of the liver, with one animal showing accentuated lobular pattern, yellow staining or ulceration of the glandular gastric epithelium, gaseous distension of the stomach and congestion of the small intestine.
250 mg/kg/day: dark liver and kidneys and gaseous distension of the stomach. One female also showed a reddened glandular gastric epithelium at necropsy.
50 mg/kg/day: no macroscopic abnormalities were detected

Applicant's summary and conclusion

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dose levels for the main twenty-eight day study were chosen as:
High dose: 200 mg/kg/day
Intermediate dose: 50 mg/kg/day
Low dose :15 mg/kg/day
- plus a control group treated with vehicle only
Executive summary:

To establish the maximum tolerated dose level (up to 1000 mg/kg/day) of the test material Chloroacetaldehyde dimethylacetal equivalent to OECD Guideline 401 following repeated oral administration to the Sprague-Dawley CD strain rat, and to establish a low dose level that does not produce evidence of toxicity. This information will be used to determine dose levels for use in a twenty-eight day oral toxicity study. This study can be found in appendix XIII in the test report "28 Day sub-acute oral toxicity study in the rat"