ferrocene, (4-chlorobutyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 June - 14 October 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[2-(4-chlorobutyl)cyclopenta-2,4-dien-1-yl](cyclopenta-2,4-dien-1-yl)iron

EC Number:

604-247-0

Cas Number:

141719-29-1

Molecular formula:

C14H17ClFe

IUPAC Name:

[2-(4-chlorobutyl)cyclopenta-2,4-dien-1-yl](cyclopenta-2,4-dien-1-yl)iron

Test material form:

liquid

Details on test material:

Appearence: brown-red liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: SNPE / LD 2332
- Appearence: brown-red liquid
- Name of test item: CL 1038

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: refrigerated under nitrogen
- Solubility and stability of the test substance in the solvent/vehicle: soluble in common solvents (acetone, hexane, chlorinated solvents)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl:CD (SD) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Saint Aubin les Elbeuf, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: 142 ± 4 g for males; 124 ± 3 g for females
- Fasting period before study: 18 h before administration
- Housing: 5 of the same sexe/cage; polycarbonate cage
- Diet (e.g. ad libitum): ad libitum (rats - souris entretien; A 04 C)
- Water (e.g. ad libitum): ad libitum (0.22 µm filtered water)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 50 ± 20 %
- Air : filtered with absolute-type filters
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: required amount for the dose
- Amount of vehicle (if gavage): administration volume of 10 mL/kg bw
- Lot/batch no. (if required): 82202
- Provider: Prolabo, Paris, France
- Appearence: colorless liquid

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

500, 800, 1400, 1100, 2500 and 5000 mg/kg bw

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: clinical signs are followed frequently during the first hours following the administration and then daily. Mortality is recorded twice daily. Bodyweight is measured just before administration, and on Days 5, 8 and 15.
- Necropsy of survivors and dead animals is performed

Statistics:

LD50 was calculated by the Finney method. The 95% confidence interval was calculated according to the Fieller method.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 211 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 066 - <= 1 385

Mortality:

See table below

Clinical signs:

other: The major dose-related clinical signs were: sedation, hypokinesia, piloerection, muscle tremors, dyspnoea, lateral decubitus, ocular secretions and ptosis. These signs were observed 30 min after administration for 4 to 6 days, depending on the dose.

Gross pathology:

No anomalies recorded in animals sacrificed at the end of the observation period.

Any other information on results incl. tables

Mortality in males and females:

Dose (mg/kg bw	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7	Day 15
500	0	0	0	0	0	0	0	0
800	0	0	0	0	0	0	0	0
1100	0	0	0	1	2	3	3	3
1400	0	0	1	1	2	6	8	8
2500	0	0	1	6	8	10	10	10

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the test conditions, the LD50 in males and females rats of the test item was calculated to be 1211 mg/kg bw. This leads to classification of the substance as category 4 (H302) for acute oral toxicity according to CLP Regulation (EC) N° (1272-2008) and GHS criteria.

Executive summary:

In a GLP study conducted according to OECD guideline 401, groups of 5 male and 5 female Sprague-Dawley rats were given a single dose of the test item suspended in PEG300 at the doses of 500, 800, 1400, 1100, 2500 and 5000 mg/kg bw. All animals were observed for mortality, clinical signs and bodyweights for 14 days and survivors were sacrificed for macroscopic examination.

The major dose-related clinical signs were: sedation, hypokinesia, piloerection, muscle tremors, dyspnoea, lateral decubitus, ocular secretions and ptosis. These signs were observed 30 min after administration for 4 to 6 days, depending on the dose. Normal evolution was observed at 500, 800 and 1100 mg/kg bw. A slight and important decrease in bodyweight is recorded on Day 5 at 1400 and 2500 mg/kg bw, respectively. Mortality was observed from 1100 mg/kg bw and above, in both sexes.

Under the test conditions, the LD50 in males and females rats of the test item was calculated to be 1211 mg/kg bw. This leads to classification of the substance as category 4 (H302) for acute oral toxicity according to CLP Regulation (EC) N° (1272-2008) and GHS criteria.