Hexachlorocyclopentadiene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 20 August 1986 to 3 September 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

doses different from the ones currently recommended

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Limit test:

no

Test material

Test material information

1

Reference substance name:

Hexachlorocyclopentadiene

EC Number:

201-029-3

EC Name:

Hexachlorocyclopentadiene

Cas Number:

77-47-4

Molecular formula:

C5Cl6

IUPAC Name:

hexachlorocyclopentadiene

Test material form:

liquid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Stored at ambient temperature in the original containers
- Stability under test conditions: Stability and absorption of the test substance were not determined

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Hexachlorocyclopentadiene was prepared at various (w/v) concentrations in corn oil and administered at a volume of 10.0 mL/kg

Test animals

Species:

rat

Strain:

other: CFY (Sprague-Dawley)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd., Huntingdon, Cambridgeshire, England
- Age at study initiation: approximately 4-6 weeks
- Weight at study initiation: 103 - 137 g
- Fasting period before study: access to food prevented overnight prior to and approximately 4 hours after dosing
- Housing: housed in groups by sex in metal cages with wire mesh floors; accommodated with forced-ventilation whole-body inhalation chambers (40" x 36" x 37.5")
- Diet: standard laboratory rodent diet (Labsure LAD 1) provided ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: mean daily minimum and maximum temperatures were 18 °C and 20 °C respectively
- Humidity: mean daily relative humidity was 63%
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hours artificial light in each 24 hour period

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 12.6% (w/v); 16.0% (w/v); 20.0% (w/v)
- Amount of vehicle (if gavage): 10.0 mL/kg

Doses:

1,260 mg/kg; 1,600 g/kg; 2,000 g/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed soon after dosing, then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs; body weight; approximate time of death; nature, severity, time of onset and duration of each toxic sign

Statistics:

Separate LD50 values for males and females were estimated by undertaking probit analysis on the mortality data by fitting two parallel lines on the data (males only and females only) using the technique described by Finney (1978, Statistical Method in Biological Assay, 3rd Edition, Charles Griffin, London). A chi-squared test was carried out to check that the data did not contain any evidence for non-parallelism.

Results and discussion

Preliminary study:

A trial test was carried out to establish a dosing regimen, using groups of 2 males and 2 female rats, at dose levels of 50, 100, 200, 500, 1260, 2500 and 5000 mg/kg bw. Results of this preliminary study indicated that the acute median lethal oral dose was between 1.26 and 2.5 g/kg bodyweight

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 400 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 200 - <= 1 500

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 500 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 300 - <= 1 700

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1 300 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 000 - <= 1 500

Mortality:

Deaths among male/female rats given doses of 1.26 g/kg and above. Mortalities generally occurred on days 2 or 3 but additional single female rats dosed at 1.26 g/kg were found dead on Days 4 and 12.

Clinical signs:

Signs of reaction to treatment observed in all rats shortly after dosing were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiration, ptosis, pallor of the extremities and diarrhoea. In addition a high-stepping gait was observed amond the female rats dose at 1.26 g/kg and two males dosed at 2.00 g/kg were prostate before their demise. Recovery of survivors, as judged by external appearance and behaviour, was completed at various times between Days 6 and 11.

Body weight:

Bodyweight losses or no change of bodyweight (in one case) were recorded for the rats that died. Low bodyweight gains were recorded on Day 8 for all rats that survived the effects of treatment. All rats achieved at least the anticipated bodyweight gain during the second week of the observation period.

Gross pathology:

Terminal autopsy findings were normal.

Any other information on results incl. tables

See attached background material for full results tables of mortality data and observations, including mortality response curve.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study determined the LD50 of male and female rats to be 1400 mg/kg bw, which meets the GHS criteria for classification as acute toxicity hazard Category 4.

Executive summary:

The acute oral toxicity of hexachlorocyclopentadiene was determined according to EPA OTS 798.1175, and was equivalent to the OECD Guideline for Testing of Chemicals 401, with deviations. The study was non GLP compliant. The study was carried out on male and female CFY Sprague-Dawley rats, which were administered appropriate doses of the test substance via oral gavage. Rats were observed for 14 days after dosing and observations on mortality, clinical signs, bodyweight and terminal autopsy were recorded. The study determined the LD50 of male and female rats to be 1400 mg/kg bw, which meets the GHS criteria for classification as acute toxicity hazard Category 4.