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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Cross-referenceopen allclose all
Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: no guideline study; 1 hr exposure time; non-GLP
Qualifier:
no guideline followed
Principles of method if other than guideline:
Exposure to the substance for 1 hr, room temperature, total air flow: 10.0 lpm (no further information), up to 14 d post exposure observation, gross necropsy
GLP compliance:
no
Test type:
traditional method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
no further data
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
no further data
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
ca. 1 h
Concentrations:
0.71 mg/L
No. of animals per sex per dose:
6 male rats
Control animals:
no
Details on study design:
no further data
Statistics:
no data
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 0.71 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Mortality:
no
Clinical signs:
no
Body weight:
initial mean body weight: 218 g, terminal mean body weight: 270 g
Gross pathology:
no findings
Other findings:
no further data
Interpretation of results:
study cannot be used for classification
Conclusions:
LC50 > 0.71 mg/L for 1 h
Executive summary:

Following exposure of rats against 0.71 mg/L p-cresol for 1 hour, no rat died and no clinical findings were reported.

Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: no information about strain used, exposure time: 1 hr, only one concentration
Qualifier:
no guideline followed
Principles of method if other than guideline:
6 rats exposed to 0.71 mg/L for 1 hr, room temperature, up to 14 d post exposure observation, gross necropsy
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 212 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
CONDITIONS:
Room temperature
Total air flow: 10.0 lpm
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
ca. 1 h
Concentrations:
0.71 mg/L
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations daily
- weighing: at the end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology
Statistics:
no data
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 0.71 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Mortality:
0/6
Clinical signs:
none mentioned
Body weight:
mean weight: initial: 212 g; at termination of the study: 256 g
Gross pathology:
no significant findings
Other findings:
none
Interpretation of results:
study cannot be used for classification
Conclusions:
LC50 > 0.71 mg/L for 1h
Executive summary:

No mortality occurred following the exposure of 6 rats to 0.71 mg/L for 1 hr and within the 14 day observation period. Clinical signs or findings following sacrifice were not reported.

Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary citation from peer-reviewed data source. No detail of exposure duration.
Principles of method if other than guideline:
aerosol-exposure; no further data
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no further data
Type of inhalation exposure:
not specified
Vehicle:
not specified
Details on inhalation exposure:
no further data
Concentrations:
no data
Key result
Sex:
not specified
Dose descriptor:
LC50
Effect level:
58 mg/m³ air
Based on:
test mat.
Mortality:
50% of the rats in test
Clinical signs:
irritation of the mucous membranes, neuromuscular excitation, and convulsions
at very high doses (not further specified): haematuria
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
study cannot be used for classification
Conclusions:
LC50 value = 58 mg/m³
Executive summary:

In rats, the LC50 value of 58 mg/m³ resulted from exposure against m-cresol aerosols (exposure time not mentioned). Clinical signs reported included irritation of the mucous membranes, neuromuscular excitation and convulsions.

Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study based on accepted scientific principles, of limited use for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Inhalation hazard test: Exposure to an atmosphere enriched with the test substance at ambient temperature
GLP compliance:
no
Test type:
other: inhalation risk test
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. A. Ivanovas, Kisslegg/Allgäu/Germany
- Age at study initiation: no data
- Weight at study initiation: 115 - 140 g (male, female)
- Fasting period before study: 16
- Housing: 5 per cage
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Air-conditioned room
- Temperature (°C): 22 +- 1 °C
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass tube
- Exposure chamber: 150 mm (diameter) x 1000 mm (length)
- Method of holding animals in test chamber: in a segment of the inhalation tube
- Source and rate of air: micro-filtered pressure air
- Method of conditioning air: passed through a layer of 5 cm finely granulated test substance
- air rate: 480 L/h (L/min)
- Treatment of exhaust air: exhaust hood
- Temperature, humidity, pressure in air chamber: 24 °C
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 h
Concentrations:
no data, test-substance enriched air (24 °C): < saturation concentration (Cs)
Cs = ~ 0.13 mg/L (based on a vapour pressure of 0.027 hPa at 25 °C and the molecular mass of 122 g/mol)
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: 1x/day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.07 mg/L air
Based on:
test mat.
Exp. duration:
7 h
Remarks on result:
other: estimated air concentration (as gas) based on saturation (~ 1.3 mg/L), assuming 50 % air saturation under test conditions.
Mortality:
none
Clinical signs:
no particular observations
Body weight:
normal
Gross pathology:
no particular findings
Interpretation of results:
study cannot be used for classification
Conclusions:
LC 50 > 0.07 mg/L following 7 h exposure
Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: only one dose, individual animal data not shown, exposure period: 1 hour
Qualifier:
no guideline followed
Principles of method if other than guideline:
room temperature, total air flow: 10.0 lpm (no further information) observation for clinical signs and mortality, gross autopsy
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
no further data
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
other: air
Details on inhalation exposure:
no further data
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
1 h
Concentrations:
1.22 mg/L
No. of animals per sex per dose:
6 male rats
Control animals:
not specified
Details on study design:
no further data
Statistics:
no data
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1.22 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Mortality:
no
Clinical signs:
generalized inactivity, lacrimation; onset: 15 - 30 minutes; recovery at treatment day
Body weight:
initial mean body weight: 197 g; terminal mean body weight: 250 g
Gross pathology:
no significant findings
Other findings:
no further details

no further details

Interpretation of results:
study cannot be used for classification
Conclusions:
LC50 > 122 mg/L/1h air
Executive summary:

Exposure of male rats to the test substance for 1 hour and postexposure observation for clinical signs and mortality resulted in no mortality, but generalized inactivity: LC50 > 1.22 mg/L/1h air.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
LC50
Remarks:
rat
Effect level:
> 1.22 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Remarks on result:
other: Source, CAS 95-48-7, o-cresol, IBTL, 1969

Any other information on results incl. tables

In the result table above the most critical value of the weight of evidence approach is given. In the following, the results are shown for the other source substances of this weight of evidence approach:

Source CAS 106 -44 -5: p-cresol: LC50 (male, rat) > 0.71 mg/L air (1 h exposure duration); IBTL, 1969

Source CAS 108 -39 -4: m-cresol: LC50 (male, rat) > 0.71 mg/L air (1 h exposure duration); IBTL, 1969

Source CAS 108 -39 -4: m-cresol: LC50 (sex not specified, rat) 58.0 mg/m³ air (exposure duration not specified); Pereima, 1975

Source CAS 108 -68 -9: 3,5 -xylenols: LC50 (male/female, rat) > 0.07 mg/L air; (7 h exposure duration), estimated air concentration (as gas) base on saturation (~ 1.3 mg/L), assuming 50% air saturation under test conditions; (Rütgers, 1981)

Applicant's summary and conclusion

Interpretation of results:
other: overall data base is not sufficient for a final conclusion
Conclusions:
Based on all available information (weight-of-evidence) and following an analogue read-across approach the data does not allow a final conclusion on acute inhalation toxicity. Further testing is, however, not required, because Tar acids, Xylenol fraction (CAS 84989-06-0) is evaluated as corrosive in a worst-case approach and classified / labelled accordingly. This is in accordance with the specific rules (Column 2) of Annex VIII No. 8.5 of Regulation (EC) No. 1907/2006 (REACH): acute toxicity studies do not generally need to be conducted if the substance is classified as corrosive to the skin.
Executive summary:

Studies on cresol isomers and 3,5-xylenol are available, but the quality of the data does not allow a final conclusion on acute inhalation toxicity. Further testing is, however, not required, because Tar acids, Xylenol fraction (CAS 84989-06-0) is evaluated as corrosive in a worst-case approach and classified / labelled accordingly. This is in accordance with the specific rules (Column 2) of Annex VIII No. 8.5 of Regulation (EC) No. 1907/2006 (REACH): acute toxicity studies do not generally need to be conducted if the substance is classified as corrosive to the skin.