Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30.9.-16.10.2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,1,1,2,3-pentachloropropane
- Substance type: organic
- Physical state: liquid
- Analytical purity: 99.940 % (w/w)
- Impurities (identity and concentrations): chlorinated hydrocarbons - 0.048 % (w/w)
- Lot/batch No.: 2-750
- Expiration date of the lot/batch: august 2014
- Storage condition of test material: dry place at room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeding farm VELAZ, s.r.o., Koleč u Kladna, Czech Republic,
- Age at study initiation: 8-12 weeks at the time application
- Weight at study initiation: 182.8 - 221.4 g
- Fasting period before study: 20 hours
- Housing: animal room with monitoring conditions – 3 animals of one sex in one plastic breeding cage Velaz T4
- Diet (e.g. ad libitum): ST 1 BERGMAN – standard pelleted diet ad libitum
- Water (e.g. ad libitum): drinking tap water ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C (permanently monitoring)
- Humidity (%): 30 - 70 % (permanently monitoring)
- Photoperiod (hrs dark / hrs light): 12-hour light/12 hour dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle and amount of vehicle (if gavage): Concentration of the test material was chosen so that the dose volume was 1mL/100 g of animal body weight.
- Lot/batch no. (if required): 5211201
Doses:
300 mg/kg body weight
2000 mg/kg body weight
No. of animals per sex per dose:
3 animals / sex/ dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of clinical observations: daily
- Frequency of weighing: before application, 8th day and before euthanasia of animals
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg: 1 animal died and 2 animals were humanely sacrificed by reason of moribund condition
300 mg/kg: no mortality
Clinical signs:
see Table No. 2
Body weight:
see Table No. 1
Gross pathology:
Animal No.: 1 (2000 mg/kg) - anaemic skin, fur stained by urine, cachexy, reddish brown lacrimation and discharge from nostril, endophtalmus, hyperemia of stomach with red punctiform foci (diameter 0,5 mm), liver marked structure, thoracic and abdominal cavity smelled by the test substance.

Animal No.: 2 (2000 mg/kg) - anaemic skin, fur stained by urine, cachexy, reddish brown lacrimation and discharge from nostril, endophtalmus, hyperemia of stomach with red punctiform foci (diameter 0,5 mm), liver marked structure, thoracic and abdominal cavity smelled by the test substance.

Animal No.: 3 (2000 mg/kg) - anaemic skin, fur stained by urine, cachexy, reddish brown lacrimation and discharge from nostril, endophtalmus, hyperemia of stomach with red punctiform foci (diameter 0,5 mm), liver marked structure and anaemic, thoracic and abdominal cavity smelled by the test substance.

Animals No.: 4 - 9 (300 mg/kg) - without pathologic changes

Any other information on results incl. tables

Table No. 1: Body weight

Dose   (mg/kg) 

(Step No.)

Animal

No.

Body weight (g)

Before
application

2 days
p.a.

15 days
p.a.

2000

(1)

1

213.7

204.8

-

2

197.9

192.6

-

3

 182.8

176.1

-

300

(2)

4

221.4

249.4

261.4

5

191.1

211.9

220.2

6

202.4

224.3

233.0

300

(3)

7

204.8

239.9

252.2

8

190.8

215.3

227.0

9

         194.0

226.6

236.1

Table No. 2: Clinical observation

Dose (mg/kg)

Animal

No.

Death after

application

Observed changes

2000

1

Yes

30 minutes: piloerection, gibbous posture, apathy, lurch walking and pulling pelvis legs, no response to stimuli, bradypnoea

3 hours:piloerection, gibbous posture, apathy, lurch walking and pulling pelvis legs, no response to stimuli, bradypnoea

2ndday morning:anaemic skin, fur stained by urine, anaemic visible mucouse membrane, abdominal position and apathy, immobility, reddish brown discharge from nostril and lacrimation

2000

2

Humanely sacrificed

(2ndday)

30 minutes: piloerection, gibbous posture, apathy, lurch walking and pulling pelvis legs, no response to stimuli, bradypnoea

3 hours:piloerection, gibbous posture, apathy, lurch walking and pulling pelvis legs, no response to stimuli, bradypnoea

2ndday morning:anaemic skin, fur stained by urine, anaemic visible mucouse membrane, abdominal position and apathy, immobility, reddish brown discharge from nostril and lacrimation, no response to stimuli, bradypnoe

2000

3

Humanely sacrificed

(2ndday)

30 minutes: piloerection, gibbous posture, apathy, lurch walking and pulling pelvis legs, no response to stimuli, bradypnoea

3 hours:piloerection, gibbous posture, apathy, lurch walking and pulling pelvis legs, no response to stimuli, bradypnoea

2ndday morning:anaemic skin, fur stained by urine, anaemic visible mucouse membrane, abdominal position and apathy, immobility, reddish brown discharge from nostril and lacrimation, no response to stimuli, bradypnoea

300

4

No

30 minutes: piloerection, gibbous posture

3 hours:piloerection, gibbous posture, decreased reaction to stimuli,reddish brown lacrimation

2ndday morning: reddish brown discharge from nostril

2ndday afternoon -14thday:no clinical signs of intoxication

300

5

No

30 minutes: piloerection, gibbous posture

3 hours:piloerection, gibbous posture, decreased reaction to stimuli,reddish brown lacrimation

2ndday morning: reddish brown discharge from nostril

2ndday afternoon -14thday:no clinical signs of intoxication

300

6

No

30 minutes: piloerection, gibbous posture

3 hours:piloerection, gibbous posture, decreased reaction to stimuli,reddish brown lacrimation

2ndday morning: reddish brown discharge from nostril

2ndday afternoon -14thday:no clinical signs of intoxication

300

7

No

30 minutes: piloerection, gibbous posture

3 hours:piloerection, gibbous posture, decreased reaction to stimuli,reddish brown lacrimation

2ndday morning: reddish brown discharge from nostril

2ndday afternoon -14thday:no clinical signs of intoxication

300

8

No

30 minutes: piloerection, gibbous posture

3 hours:piloerection, gibbous posture, decreased reaction to stimuli,reddish brown lacrimation

2ndday morning: reddish brown discharge from nostril

2ndday afternoon -14thday:no clinical signs of intoxication

300

9

No

30 minutes: piloerection, gibbous posture

3 hours:piloerection, gibbous posture, decreased reaction to stimuli,reddish brown lacrimation

2ndday morning: reddish brown discharge from nostril

2ndday afternoon -14thday:no clinical signs of intoxication

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance administered at the dose of 2000 mg/kg caused death of one animal and two animals were humanely sacrificed by reason of moribund condition on the 2nd day morning.
The clinical signs of intoxication - piloerection, gibbous posture, apathy, lurch walking and pulling pelvis legs, no response to stimuli, bradypnoea were detected in all animals 30 minutes and 3 hours after application.
The further clinical signs of intoxication were observed 2nd day after application: anaemic skin (piloerection disappeared), fur stained by urine, anaemic visible mucouse membrane, abdominal position and apathy instead of gibbous posture, immobility (instead of lurch walking and pulling pelvis legs), no response to stimuli, reddish brown discharge from nostril and lacrimation, bradypnoe.
During pathological examination the following changes were observed in all animals: anaemic skin, fur stained by urine, cachexy, reddish brown lacrimation and discharge from nostril, endophtalmus, hyperemia of stomach with red punctiform foci (diameter 0,5 mm), liver marked structure in all animals and anaemic in one female. The thoracic and abdominal cavity of all three animals smelled by the test substance.
The test substance administered at the dose of 300 mg/kg caused no death in any of two administered groups of females (group No. 2 and No. 3).
Clinical signs of intoxication (piloerection, gibbous posture) were observed 1st day of the study in all six animals. The reddish brown lacrimation and decreased response to stimuli were observed 3 hours after application. The reddish brown discharge from nostril was observed 2nd day morning in all six animals. No pathologic macroscopic changes were diagnosed during pathological examination.
According to the study results the value of LD50 of the test substance, 1,1,1,2,3 - Pentachloropropane, for female rats is in the range > 300 mg/kg to ≤ 2000 mg/kg.
Executive summary:

The aim of the study was to investigate acute toxic effects of the test substance 1,1,1,2,3 - Pentachloropropane, after a single oral administration to Wistar rats.

The testing was performed according to the Method B.1 tris: Acute Oral Toxicity - Acute Toxic Class Method, Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008 and OECD Test Guideline No. 423: Acute Oral Toxicity – Acute Toxic Class Method (Adopted 17th December 2001).

The test substance was administered in a single dose as solution in vehicle (olive oil), given orally via gavage to female Wistar rats. The dosing was performed sequentially in three groups of three females: group No. 1 (first step) using the starting dose of 2000 mg/kg body weight, group No. 2 (second step) and group No. 3 (third step) using a dose of 300 mg/kg body weight. The volume of administered solution was 1 ml/100 g body weight of animals.

The test substance administered at the dose of 2000 mg/kg caused death of one animal and two animals were humanely sacrificed by reason of moribund condition on the 2nd day morning.

The clinical signs of intoxication - piloerection, gibbous posture, apathy, lurch walking and pulling pelvis legs, no response to stimuli, bradypnoea were detected in all animals 30 minutes and 3 hours after application.

The further clinical signs of intoxication were observed 2nd day after application: anaemic skin (piloerection disappeared), fur stained by urine, anaemic visible mucous membrane, abdominal position and apathy instead of gibbous posture, immobility (instead of lurch walking and pulling pelvis legs), no response to stimuli, reddish brown discharge from nostril and lacrimation, bradypnoea.

During pathological examination the following changes were observed in all animals: anaemic skin, fur stained by urine, cachexy, reddish brown lacrimation and discharge from nostril, endophtalmus, hyperemia of stomach with red punctiform foci (diameter 0,5 mm), liver marked structure in all animals and anaemic in one female. The thoracic and abdominal cavity of all three animals smelled by the test substance.

The test substance administered at the dose of 300 mg/kg caused no death in any of two administered groups of females (group No. 2 and No. 3).

Clinical signs of intoxication (piloerection, gibbous posture) were observed 1st day of the study in all six animals. The reddish brown lacrimation and decreased response to stimuli were observed 3 hours after application. The reddish brown discharge from nostril was observed 2nd day morning in all six animals. No pathologic macroscopic changes were diagnosed during pathological examination. 

According to the study results the value of LD50 of the test substance, 1,1,1,2,3 - Pentachloropropane, for female rats is in the range > 300 mg/kg to ≤ 2000 mg/kg.