Registration Dossier

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 study in accordance to OECD GL

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1,1,3,3-pentachlorobutane
EC Number:
244-691-9
Cas Number:
21981-33-9
Molecular formula:
C4H5Cl5
IUPAC Name:
1,1,1,3,3-pentachlorobutane
Details on test material:
- Name of test material (as cited in study report): 1,1,1,3,3-pentachlorobutane
- Molecular formula (if other than submission substance): same as submission substance
- Molecular weight (if other than submission substance): same as submission substance
- Smiles notation (if other than submission substance): same as submission substance
- Substance type: organic
- Physical state: liquid
- Analytical purity: 90%
- Purity test date: 09/09/99
- Lot/batch No.: 99350L08
- Expiration date of the lot/batch: 13/09/2000
- Stability under test conditions: stable
- Storage condition of test material: at room temeprature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland
- Age at study initiation: 10-13 weeks old
- Weight at study initiation: males 360-470 g; females 200-270 g
- Fasting period before study: overnight befoere dosing up to 3-4 hours after dosing
- Housing: individual housing in the pilot study and group housing of 5 rats/sex/cage in the main study
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 30-70%
- Air changes (per hr): 15/h
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From:26/10/99 To: 10/12/99

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Vehicle was used only for the lowest concentration tested (50 mg/kg bw). the test substance was dosed uin the vehicle at a concentration of 25 mg/ml
- Amount of vehicle (if gavage): 2ml/kg
- Justification for choice of vehicle: selected based on a pretest carried out at Notox
- Lot/batch no. (if required): not reported
- Purity:


MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg
Doses:
5000, 2000, 500 and 50 mg/kg
No. of animals per sex per dose:
pilot study: 1 female at 5000 mg/kg
main study: 5 rat/sex at 5000 mg/kg, 2 rats/sex at 2000 and 50 mg/kg, 5 rats/sex at 50 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: at fixed intervals on day 1, daily during the observation period; body weighing: day 1, 2, 3, 4, 8 and 15 and at death (if after day 1)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy
Statistics:
not performed

Results and discussion

Preliminary study:
1 female rat dosed at 5000 mg/kg was killed moribund on day 4.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 50 - < 500 mg/kg bw
Based on:
test mat.
Mortality:
10/10 rats dosed at 5000 mg/kg died within day 2. 2/2 rats dosed at 2000 mg/kg and 500 mg/kg died within day 3 and 4, respectively. No mortality was observed at 50 mg/kg
Clinical signs:
Lethargy, hunched posture, uncoordinated movements, ptosis, clonic spasms and ventrolateral recumbency were the most common observations reported for animals dosed at >=500 mg/kg.
At 50 mg/kg uncoordinated movements were observed in 2 females on day 1, but no other findings were observed in the remaining males and females of this group
Body weight:
The bodyweight gain observed in the surviving animals durnig the observation period was considered to be similar to that expected for non treated animals.
Gross pathology:
Severe lesions were observed in the stomach at >= 500 mg/kg. Among them Irregular surface of the glandular mucosa and dark red foci, thickening and hemorrages in the glandular mucosa were reported.

No macroscopic abnormalities were observed at 50 mg/kg.

Any other information on results incl. tables

The incidence of mortality was:

5000 mg/kg: 5/5 males and 5/5 females

2000 mg/kg: 2/2 females

500 mg/kg: 2/2 females

50 mg/kg: 0/5 males and 0/5 females

Clinical signs:

5000 mg/kg: Lethargy, hunched posture, uncoordinated movements, piloerection, ptosis, clonic spasms and/or ventro lateral recumbency.

2000 mg/kg: Lethargy, hunched posture, uncoordinated movements, piloerection, ptosis, clonic spasms, ventro lateral recumbency and/or animal was pale.

500 mg/kg: Lethargy, hunched posture, piloerection, clonic spasms, alopecia and/or red stainingof the snout

50 mg/kg: Uncoordinated movements in 2 females on day 1. No clinical signs noted in the other male and female rats. Pathology 5000 mg/kg: Stomach, irregular surface of the glandular mucosa and dark red foci. Mesenteric lymph node, dark red foci. Thymus, dark red foci. 2000 mg/kg: Stomach, thickening of the limiting ridge and hemorrages of the glandular mucosa. Kidney, dark red discolouration of the medulla. 500 mg/kg: Stomach, irregular surface of the glandular mucosa, thickening. Thymus, reduced in size. 50 mg/kg: no abnormality recorded.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the mortality results, the LD50 was determined within the range 50-500 mg/kg.
The study results warrant a classification as Xn R22 (harmful if swallowed) under Directive 67/548/EEC and as Acute toxicity Category 3 (H301: Toxic if swallowed) under Regulation (EC) No 1272/2008.
Executive summary:

The oral acute toxicity of 1,1,1,3,3 -pentachlorobutane was assessed by means of a fixed dose method.

Rats were dosed at 5000, 2000, 500 and 50 mg/kg. Mortality was observed at >=500 mg/kg, with a LD50 determined within the range 50 -500 mg/kg.