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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From February 24th to March 10th, 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according 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
Chemical structure
Reference substance name:
Chlorphenesin
EC Number:
203-192-6
EC Name:
Chlorphenesin
Cas Number:
104-29-0
Molecular formula:
C9H11ClO3
IUPAC Name:
3-(4-chlorophenoxy)propane-1,2-diol
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, away from the light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: IFFA-CREDO (69210 L'ARBRESLE, FRANCE)
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: about 6 weeks
- Weight at study initiation: weight between 172 g and 194 g (males) and 173 g and 190 g (females)
- Fasting period before study: animals have been fasted prior to substance administration by withholding food overnight.
- Housing: 5 animals by sex in polypropylene cages (310 x 465 x 190 mm)
- Diet (e.g. ad libitum): maintenance diet UAR A04-10 but no specified ad libitum
- Water (e.g. ad libitum): not specified
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS: not specified

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % carboxymethylcellulose aqueous gel
Details on oral exposure:
The test substance was diluted in 0.5 % carboxymethylcellulose aqueous gel and the volume administered by gavage was 10 ml/kg of preparation.

Doses:
5 doses (1200, 1620, 2187, 2952 and 3985 mg/kg). The doses were chosen based on the resuls of preliminary test.
No. of animals per sex per dose:
10 animals per dose (5 males and 5 females). Total number of animals used in the test: 50 animals.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the deaths are registered between 2 hours and 24 hours after the treatments and at the termination of 14 observation days. A clinical observation is carried out at least once a day in order to follow the general appearance, the behaviour and vegetative functions of the animals. An individual clinical observation is realized one hour after treatment. The continuous observations during the five hours following the ingestion are renewed each following day. Body weight are taken just prior to the test material administration (D1) and again 3, 7 and 14 days after the treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical observation and body weight during observation period; gross pathological changes were recorded post mortem but no tissues were saved.
Statistics:
Calculation of upper and lower limits for p=0.05 limit for L50 oral route.

Results and discussion

Preliminary study:
The doses were chosen according to the results obtained with the product at the time of preliminary tests at the doses of 1000, 1500, 2000 et 3000 mg/kg by oral route.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 3 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Limits for p=0.05 2830-3180 mg/kg/bw
Mortality:
Dose 1200 mg/kg (group 1): no mortality
Dose 1620 mg/kg (group 2): 2 deaths (female animals) between 2-3 hours after treatment and 1 death (female animal) between 6-24 hours after treatment (total: 3 deaths on 10 animals: 30%)
Dose 2187 mg/kg (group 3): 4 deaths (3 female animals+ 1 male animal) between 2-3 hours after treatment (total: 4 deaths on 10 animals: 40%)
Dose 2952 mg/kg (group 4): 3 deaths (2 female animals+ 1 male animal) between 2-3 hours after treatment and 1 death (male animal) between 6-24 hours after treatment (total: 4 deaths on 10 animals: 40%)
Dose 3985 mg/kg (group 5): 5 deaths (3 female animals+ 2 male animals) between 2-3 hours after treatment , 1 death (male animal) between 3-6 hours after treatment and 2 deaths (male animals) between 6-24 hours after treatment (total: 8 deaths on 10 animals: 80%)
The mortality rates increase with the doses administered . The deaths are registered between 2 hours and 24 hours after the treatments.
Clinical signs:
The first signs of toxicity are noticed approximately 10 minutes after the treatment for all the animals : decrease in spontaneous motor activity, respiratory difficulties, decrease in muscle tone. One hour after the gavage, these symptoms were still observed in all the rats followed up with piloerection and loss of Preyer and righting reflex.
The observations made the 5 following hours show an improvement of the general state of the animals of each group with the exception of the animals found dead the following day. All the others have recovered 24 hours later.
The daily examinations which were repeated during the next 12 consecutives days, failed to reveal any significant alteration in the general appearance and behaviour of the animals.
Body weight:
The individual weight growth of the surviving animals was not impaired.
Gross pathology:
The post-mortem examination was systematically carried out on the animals dead during the test or sacrificed 14 days after the treatment.This examination revealed :
- in the animals sacrificed at the end of the study, the absence of organic or tissular lesions;
- in the males and females from groups 2, 3, 4 and 5 dead in the 24 hours following the treatments, a congestion of the lungs, the presence of product in the stomach and a meteorism of the small intestine.
Other findings:
No tissue were saved post mortem.

Any other information on results incl. tables

MORTALITY

GROUP

1

2

3

4

5

DOSES(mg/kg)

1200

1620

2187

2952

3985

Animal number/sex

5M

5F

5M

5F

5M

5F

5M

5F

5M

5F

between 2 and 3 hours after

treatment

0

0

0

2

1

3

1

2

2

3

3h-6h

0

0

0

0

0

0

0

0

1

0

6h-24h

0

0

0

1

0

0

1

0

2

0

D2-D15

0

0

0

0

0

0

0

0

0

0

TOTAL

0

0

0

3

1

3

2

2

5

3

Percentage of cumulated

mortality

0

30

40

40

80

Applicant's summary and conclusion

Interpretation of results:
other: not classified for acute oral toxicity according to the CLP Regulation (EC n.1272/2008)
Conclusions:
The LD50 of the test item by oral route in the male and female rat is 3000 mg/kg ( p=0.05 2830 - 3180 mg/kg) and no classification for acute oral toxicity is required according to the CLP Regulation (EC n.1272/2008).
Executive summary:

The substance has been tested for acute oral toxicity according to OECD401.

The single oral administration of the test item in the male and female Rat produces pharmacotoxic signs similar for the 5 doses administered : dyspnea, decrease in spontaneous activity, hypotonia, piloerection and loss of reflex.

Necropsies performed on animals found dead reveal mainly an intestinal meteorism and lung congestion.

From mortality data obtained, the LD50 of the test item by oral route in the male and female Rat is 3000 mg/kg (2830 - 3180 mg/kg).

LD0 is greater than 1200 mg/kg.

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