Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: inhalation
Remarks:
other: no data
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Repeated facial palsies after chlorocresol inhalation
Author:
MARTIN DOSSING, CHRISTIAN HERTEL WULFF, POUL ZANDER OLSEN
Year:
1986
Bibliographic source:
Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:1452-1454

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
The effect of exposure to chlorocresol was studied in 42 years old female
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): chlorocresol
- Substance type: Organic
- Physical state: solid

Test animals

Species:
other: Human
Sex:
female

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
other: water
Details on inhalation exposure:
A few drops of a 0-1% concentration of chlorocresol diluted in water was poured into a sink, the cold tap was turned on to ensure a water born aerosol and the patient was placed near the sink.
Duration of treatment / exposure:
3 min
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1%
Basis:

Control animals:
no

Examinations

Observations and examinations performed and frequency:
NEUROBEHAVIOURAL EXAMINATION: Yes

Results and discussion

Results of examinations

Clinical signs:
not examined
Mortality:
not examined
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:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
NEUROBEHAVIOUR
partial left-sided facial palsy occurred preceded by a feeling of pins and needles in the left cheek and temporal region. The weakness only affected the left orbicularis oris which was severely paretic. The philtrum was pulled 3-5 mms to the right (fig). There was no weakness of eye closure nor of the musculature of the forehead. The tear production of the left eye was unaffected. The rest of the neurological examination remained normal. After half an hour the facial palsy gradually resolved.

Effect levels

Dose descriptor:
LOAEL
Effect level:
1 other: %
Based on:
test mat.
Sex:
female
Basis for effect level:
other: partial left-sided facial palsy occured

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The LOAEL value of chlorocresol in 42 years old human female was observed at dose concentration of 1%
Executive summary:

A few drops of a 0-1% concentration of chlorocresol diluted in water was poured into a sink, the cold tap was turned on to ensure a water born aerosol and the patient was placed near the sink. After approximately 3 minutes a partial left-sided facial palsy occurred preceded by a feeling of pins and needles in the left cheek and temporal region. Only muscles around the left side of the mouth were affected. On neurophysiological testing during chlorocresol provocation the only abnormality was a loss of motor units during maximal contraction of the left orbicularis oris muscle. This could be explained by a peripheral as well as a central effect. Extensive electrophysiological examination without chlorocresol provocation excluded a preexisting generalized nerve disorder and other diagnostic procedures did not give evidence of pathology involving the left facial nerve. A hyperreactive mechanism causing a transient block of the left facial nerve is proposed. Hence the LOAEL was considered to be 1%