Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August - October 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): L-2-Chloropropionic acid
- Physical state: Liquid
- Analytical purity: 90.4% w/w
- Purity test date: 30th April 1992
- Lot/batch No.: Bx 0071, ADH05138
- Expiration date of the lot/batch: Not specified
- Storage condition of test material: Not specified

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not specified

MAXIMUM DOSE VOLUME APPLIED:
- Amount of vehicle (if gavage): 10ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on a preliminary study.
Doses:
Initial dose level of 1000 mg/kg (males /females)
Additional dose levels of 200 and 1500 mg/kg (both sexes) and 500 mg/kg (females only).
No. of animals per sex per dose:
Five male and five female unless otherwise specified.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Observed for signs of systemic toxicity within 2.5 hours of dosing and again between 4 and 7 hours after dosing. Subsequent observations were made once daily or twice daily where significant signs of toxicity were observed.
- Necropsy of survivors performed: yes on day 15

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1 118 mg/kg bw
Based on:
test mat.
95% CL:
938 - ca. 1 333
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 575 mg/kg bw
Based on:
test mat.
95% CL:
307 - 938

Any other information on results incl. tables

 

 

 

 There were no signs of toxicity and no animals died after a dose of 200mg/kg L-2-Chloropropionic acid.

 

Female rats only were exposed to a dose of 500mg/kg of the test substance. Of the five rats exposed, one showed signs of extreme toxicity (e.g. decreased activity, dehydration, hypothermia, piloerection, reduced foot withdrawal reflex) and was killedin extremison day 2. Two animals showed signs of slight general toxicity (e.g. decreased activity, piloerection, pinched-in sides) and were found dead on day 4. The two animals that survived to the end of the study showed signs of slight general toxicity for up to 9 days and both animals showed reduced stability from day 2 or 3 until the end of the study.

 

Following doses of 1000 mg/kg to both male and female rats, one male and two females showed signs of extreme toxicity and were killedin extremison day 1 or 3. One female showed signs of slight to moderate toxicity but was found dead on day 3.  Surviving animals showed signs of slight to moderate toxicity similar to those seen at lower dose levels but of higher incidence. Reduced stability persisted until the end of the study in all surviving animals.

 

After dosing with 1500mg/kg, all the males and one female showed signs of slight to moderate toxicity but were never the less found dead on day 2. The remaining females showed signs of extreme toxicity and were killedin extremison days 2 or 3.

 

Post mortem findings suggested a local irritant effect on the gastrointestinal tract and a possible effect on the liver, particularly in the animals dosed at 1500 mg/kg. An incidence of blood stained urine at this dose level may also have been treatment related.

 

Table 1 shows a summary of the cumulative mortality data.

 

Table 1.

Dose Level (mg/kg)

Day Number

Number of Deaths

Male

Female

200

-

0/5

0/5

15 (total)

0/5

0/5

500

2

N/A

1/5

4

-

2/5

15 (total)

-

3/5

1000

1

1/5

1/5

3

0/5

2/5

15 (total)

1/5

3/5

1500

2

5/5

4/5

3

-

1/5

15 (total)

5/5

5/5

Applicant's summary and conclusion

Conclusions:
The acute oral median lethal dose of L-2-Chloropropionic acid was calculated to be 1118 mg/kg to male rats and 575 mg/kg to female rats.
Executive summary:

 

The acute oral toxicity of L-2-Chloropropionic acid was assessed in a guideline study on Wistar albino rats.

Groups of five male and /or five female rats received a single oral dose of 200, 500, 1000 or 1500 mg/kg of the test substance. The animals were assessed daily for signs of toxicity and their bodyweights recorded at various time points throughout the study. All animals were subjected to a macroscopic post mortem examination.

 

There were no signs of toxicity and no animals died after a dose of 200mg/kg L-2-Chloropropionic acid.

 

Female rats only were exposed to a dose of 500mg/kg of the test substance.

Three animals were found dead or were killedin extremisby day 4. The two animals that survived to the end of the study showed signs of slight general toxicity up to day 9 and reduced stability until the end of the study.

 

Following doses of 1000 mg/kg to both male and female rats, one male and three female animals were found dead or were killed in extremis on day 1 or 3. Surviving animals showed signs of slight to moderate toxicity similar to those seen at lower dose levels but with higher incidence. Reduced stability persisted until the end of the study in all surviving animals.

 

After dosing with 1500mg/kg, all the males and one female showed signs of slight to moderate toxicity but were found dead on day 2. The remaining females showed signs of extreme toxicity and were killedin extremison days 2 or 3.

 

Post mortem findings suggested a local irritant effect on the gastrointestinal tract and a possible effect on the liver, particularly in the animals dosed at 1500 mg/kg. An incidence of blood stained urine at this dose level may also have been treatment related.

 

The acute oral median lethal dose of L-2-Chloropropionic acid was calculated to be 1118 mg/kg to male rats and 575 mg/kg to female rats.