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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
The study was performed to assess the acute toxicity following oral administration of (R)-2-Chlormandelsäure in Wistar rats.
The study procedure was based on the OECD, EU and US EPA OPPTS guidelines.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): (R)-2-chloromandelic acid; Substance No.: 01/0490-1
- Physical state: Solid (crystalline) / white to slight yellowish
- Analytical purity: 99.7 area-%
- Impurities (identity and concentrations):
- Date of Production: February 07, 2002
- Lot/batch No.: T138-02-01
- Storage condition of test material: Room temperature
- Homogeneity: Homogeneous by visual inspection
- Stability: The stability under storage conditions over the exposure period was guaranteed by the sponsor.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sandhofer Weg 7, 97633 Sulzfeld
- Age at study initiation: Young adult animals (male animals approx. 8 - 12 weeks, female animals approx. 14-18 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing
- Diet: Kliba-Labordiät, Provimi Kuba SA, Kaiseraugst, Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: for at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: test substance in 0.5% carboymethylcellulose solution in doubly distilled water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 g/100 ml



MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg


DOSAGE PREPARATION:
The test substance preparation was produced for each administration group shortly before administration in 0.5% CMC-solution (cleaned sodium carboxymethylcellulose, Hoechst AG) in doubly distilled water by stirring with high speed homogenizer (Ultra-Turrax).

Doses:
2000 mg/kg
No. of animals per sex per dose:
3 male and 3 female animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Body weight determination:
Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study. Additionally, at day of death in animals that died starting with study day 1.

Signs and symptoms:
Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals; these records are maintained with the raw data.

Mortality:
A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.

Pathology:
Necropsy with gross-pathology examination on the last day of the observation period after killing with CO2. Necropsy of all animals that died before as early as possible.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One female animal was found dead on study day 1. No mortality occurred in the male animals.
Clinical signs:
Male animal symptoms
Clinical observation revealed impaired general state, dyspnoea, smeared fur and were observed from hour 2 until including study day 2 after administration.
 
Female animal symptoms
Clinical observation revealed impaired and poor general state, dyspnoea, staggering, piloerection, smeared fur, red clammy snout and were observed from hour 0 until including study day 1 after administration.
Body weight:
The mean body weights of the male animals increased throughout the study period. The mean body weights of the female animals increased during the first post exposure observation week but decreased during the second week.
Gross pathology:
The following macroscopic pathologic abnormality was observed in the animal that was found dead (1 female): lesion on the mucosal membrane of the glandular stomach with necrotizing surface. No macroscopic pathologic abnormalities were noted in the animals (3 males and 2 females) examined at termination of the study.

Any other information on results incl. tables

ANALYSES

Analysis of test substance:

The stability of the test substance in the vehicle for the preparations: maximum application period was confirmed indirectly by analysis of homogeneity analysis of the concentration. The correctness of the homogeneity of the test substance preparation for the first administration was confirmed by analysis.

 

Conduct of analyses:

The analyses were carried out at the Analytical Chemistry Laboratory of the Experimental Toxicology and Ecology of BASF AG.

 

Analysis of feed:

In view of the aim and duration of the study the contaminants occurring in commercial feed should not influence the results.

 

Analysis of drinking water:

In view of the aim and duration of the study there are no special requirements exceeding the specification of drinking water.

 

CONCLUSION

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2,000 mg/kg body weight for male and female rats.

Applicant's summary and conclusion