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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Remarks:
4-months
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Cross-reference
Reason / purpose:
read-across source
Reference
Endpoint:
sub-chronic toxicity: inhalation
Remarks:
4-months
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary literature: experimental details are missing, only one dose used
Principles of method if other than guideline:
Rats were exposed by inhalation to p-cresol.
GLP compliance:
not specified
Species:
rat
Strain:
not specified
Sex:
female
Details on test animals and environmental conditions:
no data
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Remarks on MMAD:
no data
Details on inhalation exposure:
no data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
4 months
Frequency of treatment:
daily
Dose / conc.:
0.01 mg/L air
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
Post-exposure period: 2 months
Positive control:
no data
Observations and examinations performed and frequency:
no data
Sacrifice and pathology:
no data
Other examinations:
no data
Statistics:
no data
Clinical signs:
effects observed, treatment-related
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
effects observed, treatment-related
Behaviour (functional findings):
effects observed, treatment-related
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Key result
Dose descriptor:
LOAEL
Effect level:
0.01 mg/L air
Based on:
test mat.
Sex:
female
Basis for effect level:
other: see 'Remarks'
Critical effects observed:
not specified

Clinical signs of toxicity included loss of appetite, marked emaciation and decreased locomotor activity. Irritative effects, which persisted throughout recovery, were seen on the nose, eye and skin. Decreased body weight gain and lung weight, increased liver weight, oliguria and dystrophic changes in the lung and liver occurred. 

Throughout recovery the body weights remained depressed and urinary excretion remained low.

Conclusions:
Female rats were exposed to p-cresol aerosols. Clinical signs of toxicity included loss of appetite, marked emaciation and decreased locomotor activity. Irritative effects, which persisted throughout recovery, were seen on the nose, eye and skin. Decreased body weight gain and lung weight, increased liver weight, oliguria and dystrophic changes in the lung and liver occurred. Throughout recovery the body weights remained depressed and urinary excretion remained low.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Administration / exposure

Remarks on MMAD:
no data
Frequency of treatment:
daily

Results and discussion

Effect levels

Key result
Dose descriptor:
LOAEL
Remarks:
rat
Effect level:
0.01 mg/L air
Based on:
test mat.
Sex:
female
Basis for effect level:
other: see 'Remarks'
Remarks on result:
other: Source, CAS 106-44-5, p-cresol, Pereima, 1975

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Due to the lack of further information on this study with p-cresol and to the fact that only limited data on p-cresol are available, the data base is very limited and does not allow a final conclusion on repeated dose inhalation toxicity of Tar acids, Xylenol fraction (CAS 84989-06-0). However, further testing is not required as there are reliable oral repeated dose toxicity data available for the hazard assessment and therefore, the requirements defined in Regulation (EC) No 1907/2006, Annex IX, 8.6 are fulfilled.
Executive summary:

Female rats were exposed to p-cresol aerosols. Clinical signs of toxicity included loss of appetite, marked emaciation and decreased locomotor activity. Irritative effects, which persisted throughout recovery, were seen on the nose, eye and skin. Decreased body weight gain and lung weight, increased liver weight, oliguria and dystrophic changes in the lung and liver occurred. Throughout recovery the body weights remained depressed and urinary excretion remained low. Due to the lack of further information on this study and to the fact that only limited data on p-cresol are available, the data base is very limited and does not allow a final conclusion on repeated dose inhalation toxicity of Tar acids, Xylenol fraction (CAS 84989-06-0). However, further testing is not required as there are reliable oral repeated dose toxicity data available for the hazard assessment and therefore, the requirements defined in Regulation (EC) No 1907/2006, Annex IX, 8.6 are fulfilled.