3-chloropropene

Repeated dose toxicity: other routes

Administrative data

Endpoint:

sub-chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: - non-GLP - very limited information on experimental details

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- 6 adult rabbitstreated with 3-chloropropene by subcutaneous injection, 50 mg/kg, 3 times in the first week, followed by 100 mg/kg, 3 times a week for 38-80 days, three rabbits as untreated controls
- divided into 3 groups and killed on the 38th, 54th and 80th day
- EMG measurements
- Histology on samples of the brain, cervical and lumbar spinal cord, sciatic and tibial nerves.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-chloropropene

EC Number:

203-457-6

EC Name:

3-chloropropene

Cas Number:

107-05-1

Molecular formula:

C3H5Cl

IUPAC Name:

3-chloroprop-1-ene

Details on test material:

No information was given about the test material, but as in the publication some of the results of LU 1982 were repeated and as there is an intersection in the two lists of authors it was concluded by the reviewer that they probably used the same material and therefore the information from Lu 1982 is presented here:
- Name of test material (as cited in study report): allyl chloride - Physical state: colorless liquid
- Analytical purity: either twice distilled (>99 %) or of a commercial grade with a purity of about 90%,
probably in the study presented her the 99 % pure substance was used
the use of the 90 % substance in the acute experiments was explicitely reported
- Lot/batch No.: not reported
- Stability under test conditions: stable
- Storage condition of test material: not reported
Confidential details on test material

Test animals

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

unchanged (no vehicle)

Details on exposure:

Six adult rabbits were given 3-chloropropene by subcutaneous injection, 50 mg/kg, 3 times in the first week, followed by 100 mg/kg, 3 times a week for 38-80 days.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

single injection per day, 38 - 80 days

Frequency of treatment:

3 d/wk

Doses / concentrations

Remarks:

Doses / Concentrations:
50 mg/kg, 3 times in the first week, followed by 100 mg/kg,

No. of animals per sex per dose:

6 animals, 2 sacrificed after 38 d, 54 d and 80 d
3 rabbits were used as normal controls.

Control animals:

yes, concurrent no treatment

Details on study design:

no data

Examinations

Observations and examinations performed and frequency:

- EMG measurements
- Histology:
Tissue samples from the brain, cervical and lumbar spinal cord, sciatic and tibial nerves were fixed in 10% formalin and embeded with paraffin. Sections were stained with H.E. and some with Nissl's, Weil's, Gros-Bielschosky's or Masson's stain.

Sacrifice and pathology:

The animals were divided into 3 groups and killed on the 38th, 54th and 80th day.

Other examinations:

not reported

Statistics:

no data

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

EMG measurement:
EMG abnormalities were found in all dosed animals at the 5th-6th week which were correlated with the severity of functional disability.
Histology:
Morphological study by light microscopy showed that peripheral nerve fibre degeneration was most marked in the distal portions of the nerves examined, although milder fibre changes were readily seen in the proximal portions. In severely damaged nerve fibres, a number of axons and myelin sheaths undergoing Wallerian degeneration had been replaced by clusters of vacuoles and foamy cells, while the milder fibre changes were an axonal irregular moniliform swelling associated with focal demyelination.

Effect levels

Dose descriptor:

LOAEL

Effect level:

100

Sex:

not specified

Basis for effect level:

other: neurotoxic effects: peripheral nerve fibre degeneration, mainly in the distal portions of the nerves

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

In the present study (He 1985) 3 groups of 2 rabbits were treated with 100 mg/Kg bw of 3 -chloropropene via subcutaneous injection at 3 d/wk for 38, 54 and 80 d (first 3 injections only with 50 mg/Kg bw).

EMG measurements showed abnormalities in all dosed animals at the 5th-6th week which were correlated with the severity of functional disability.

Morphological study by light microscopy showed that peripheral nerve fibre degeneration was most marked in the distal portions of the nerves examined, although milder fibre changes were readily seen in the proximal portions. In severely damaged nerve fibres, a number of axons and myelin sheaths undergoing Wallerian degeneration had been replaced by clusters of vacuoles and foamy cells, while the milder fibre changes were an axonal irregular moniliform swelling associated with focal demyelination.