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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in GLP compliance and in accordance of OECD guideline 423.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Chloroacetic anhydride
EC Number:
208-794-2
EC Name:
Chloroacetic anhydride
Cas Number:
541-88-8
Molecular formula:
C4H4Cl2O3
IUPAC Name:
2-chloroacetyl 2-chloroacetate
Test material form:
other: dark brown solidified melt
Details on test material:
- Name of test material (as cited in study report): chloroacetic acid anhydride
- Physical state: solidified melt
- Analytical purity: 97.1 %
- Purity test date: 02 February 2007
- Lot/batch No.: 1028168
- Expiration date of the lot/batch: 08/2008
- Storage condition of test material: at 20°C, protected from light
- Other: pH 1.6

Test animals

Species:
rat
Strain:
other: Crl:WI(Han), SPF quality
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld, Germany,
via Biological Laboratory Services, Boehringer Ingelheim harma GmbH & Co. KG, Biberach, Germany
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: males 224 g - 250 g, females 162 g - 171 g
- Fasting period before study: withdrawn in the afternoon of Day before administration (at about 16.00 h) over night.
- Housing: barrier-protected system, cage (Noryl, type V).
- Diet (e.g. ad libitum): pelleted dry food, ad libitum
- Water (e.g. ad libitum): tap drinking water, ad libitum
- Acclimation period: 5- to 7-day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 45% - 75%
- Air changes (per hr): minimum of 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12 hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 20 mL/kg
- Purity: demineralised

Doses:
50 mg/kg and 300 mg/kg
The administration volume was 20 mL/kg in each group.
No. of animals per sex per dose:
50 mg/kg: 3 males / 3 females
300 mg/kg: 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: at arrival, during the study: at least twice daily and once on non-working days.
weighing: Day -1, Day 1, Day 2, Day 8 and Day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
other: approximate lethal dose (ALD)
Effect level:
>= 50 - <= 300 mg/kg bw
Based on:
test mat.
Mortality:
In rats, no mortality was observed subsequent to a single oral administration of 50 mg/kg.

At 300 mg/kg, female No. 251 was found dead on Day 1, 2.0 h post administration.
Immediately thereafter, rats No. 252 and No. 253 were sacrificed due to poor general condition for reasons of animal welfare
Clinical signs:
other: 50 mg/kg (males and females): Clinical signs were observed on Day 1 only and included prone position (0.25 h to 0.5 h post administration in males; at 1.0 h only in females), reduced motor activity (0.25 h to 6.0 h in males; at 2.0 h only in females) and
Gross pathology:
No gross macroscopic findings were noted at necropsy of animals administered 50 mg/kg.
At 300 mg//kg, necropsy findings in the three premature decedents comprised alterations of the stomach (discoloration of the wall in all 3
females) and the content of the colon (No. 251 and No. 252) .

Any other information on results incl. tables

At 50 mg/kg, no mortality occurred, no influence on body weight development and no necropsy findings were noted in both male and female rats. Clinical signs were observed on Day 1 only and included prone position, reduced motor activity and piloerection. Rats of both genders returned to normal on Day 2.

At 300 mg/kg, one female was found dead on Day 1, 2.0 h post administration. Immediately thereafter, the two remaining animals were sacrificed due to their poor general condition for reasons of animal welfare. Ante mortem, prone position and reduced motor activity, as well as reduced respiration rate were observed. Necropsy findings were recorded in all three female premature decedents and comprised alterations of the stomach and the content of the colon.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of the present study, no mortality was seen in rats subsequent to oral administration of chloroacetic acid anhydride at doses of 50 mg/kg, but at 300 mg/kg, all females died or were sacrificed for reasons of animal welfare.
Thus, the approximate lethal dose (ALD) for chloroacetic acid anhydride is between 50 mg/kg to 300 mg/kg for male and female rats.
Executive summary:

Objectives:

No relevant data on acute toxicity following oral administration of chloroacetic acid anhydride is available in the scientific literature.

Thus, based on the legal requirements for Workers Safety according to current German law (Gefahrstoffverordnung [Ordinance on Dangerous Substances], 23 December 2004), this study was designed to evaluate in rats the acute toxicity of chloroacetic acid anhydride subsequent to a single oral administration by gavage.

The study was performed according to the revised version of OECD Guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method, December 2001) and in accordance with the principles on Good Laboratory Practice, as described by the respective OECD Guidelines and current German law (Chemikaliengesetz [Chemicals Act], released 20 June 2002).

Study design:

Chloroacetic acid anhydride was diluted with demineralised water and administered by oral gavage (20 mL/kg) at single doses of

50 mg/kg (males and females) and 300 mg/kg (females only), to groups of Crl:WI(Han) rats, which were about 9 weeks old. Their body weight ranged from 224 g to 250 g in males and from 162 g to 171 g in females. The animals were observed for a period of 14 days post administration.

Clinical signs were evaluated frequently on the day of administration (Day 1), as well as once or twice daily thereafter. Body weight was recorded one day before administration (Day -1), and, during the observation period, on Day 1, Day 2, Day 8 and Day 15, respectively. At the end of the observation period, necropsy was performed on all animals, and all gross macroscopical changes were recorded.

Main results

At 50 mg/kg, no mortality occurred and no necropsy findings were noted. At 300 mg/kg, one out of three females was found dead on Day 1, 2.0 h post administration. Immediately thereafter, the two remaining animals were sacrificed due to their poor general condition for reasons of animal welfare.