Registration Dossier

Administrative data

Description of key information

Following single oral doses to rats the LD50 was determined 207 mg/kg bw. The LD50(dermal, rabbit) was calculated to be 301 mg/kg bw. 
The data base on acute inhaltion toxicity of p-cresol is very limited and does not allow final conclusion.

:

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No information about strain used, GLP
Principles of method if other than guideline:
5 rats/dose group, observed for symptoms for up to 14 d, afterwards 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:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
no flurther data
Doses:
100, 147, 215, 316 mg/kg bw
No. of animals per sex per dose:
5 male rat/dose
Control animals:
no
Details on study design:
no further details
Statistics:
yes, but method not mentioned
Sex:
male
Dose descriptor:
LD50
Effect level:
207 mg/kg bw
95% CL:
>= 172 - <= 250
Remarks on result:
other: hypoactivity, tremor, lacrimation, dyspnea, hemorrhagic rhinitis, conculsion, prostration
Mortality:
mortality occurred within 4 hours post dosing
100 mg/kg bw: 0/5; 147 mg/kg bw: 0/5; 215 mg/kg bw: 3/5; 316 mg/kg bw: 5/5
Clinical signs:
onset in all animals within the first 4 hours post dosing: hypoactivity, tremors, lacrimation, dyspnea, hemorrhagic rhinitis, convulsions, prostration, recovery occurred in all survivors
Body weight:
initial mean body weight ranged between 187-220 g terminal mean body of the survivor-groups: 227-229 g (no further data)
Gross pathology:
Necropsy of the rats that died revealed gastrointestinal inflammation and haemorrhage and hyperaemia of the lungs, liver and kidney.  
Survivors showed only gastrointestinal tract inflammation.
Other findings:
no further data
Doses and mortality:
100 mg/kg bw: 0/5; 147 mg/kg bw: 0/5; 215 mg/kg bw: 3/5; 316 mg/kg bw: 5/5
Signs of intoxication: hypoactivity, tremors, lacrimation, dyspnea, hemorrhagic rhinitis, convulsions, prostration, death
Necropsy of the rats that died revealed gastrointestinal inflammation and haemorrhage and hyperaemia of the lungs, liver and kidney.  
Survivors showed only gastrointestinal tract inflammation.
Executive summary:

Following single oral doses to rats the LD50 was determined 207 mg/kg bw. The observed signs of intoxication included hypoactivity, tremors, lacrimation, dyspnea, hemorrhagic rhinitis, convulsions and prostration.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
207 mg/kg bw
Quality of whole database:
The materials/methods and results are described sufficient for evaluation.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no information about strain used and no information on GLP
Principles of method if other than guideline:
5 rabbits/dose, 4 doses, exposure time not mentioned, up to 14 d observation time, gross autopsy
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no further data
Vehicle:
other: none
Details on dermal exposure:
no further data
Duration of exposure:
no data
Doses:
215, 316, 464, 681 mg/kg bw
No. of animals per sex per dose:
5 rabbits per dose
Control animals:
no
Details on study design:
no further data
Statistics:
yes, but method not mentioned
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 301 mg/kg bw
95% CL:
>= 213 - <= 426
Remarks on result:
other: tremor, salivation, sedation , severe subdermal hemorrhaging, severe erythema
Mortality:
: 215 mg/kg bw: 1/5; 316 mg/kg bw: 3/5; 464 mg/Kg bw: 4/5; 681 mg/kg bw: 5/5
Clinical signs:
signs of intoxication from 4-12 hrs post appl.: tremor, salivation sedation , recovery occurred within 3 days post application
Body weight:
initial mean body weight ranged from2.5-2.7 kg; mean terminal body weight of rabbists dosed with 215 mg/kg : 2.3 kg (no further data given)
Gross pathology:
gross autopsy: survivors: no significant findings; decedents: inflammation of kidneys
Other findings:
dermal irritation: severe subdermal hemorrhaging, severe erythema
doses and mortality:
215mg/kg bw: 1/5; 316 mg/kg bw: 3/5; 464 mg/Kg bw: 4/5; 681 mg/kg bw: 5/5
signs of intoxication from 4-12 hrs post appl.: tremor, salivation sedation, death
dermal irritation: severe subdermal hemorrhaging, severe erythema
gross autopsy: survivors: no significant findings; decedents: inflammation of kidneys
Executive summary:

To determine LD-50 value, rabbits received dermal application of 215 -681 mg/kg bw undiluted p-cresol and were observed for clinical signs of toxicity and mortality for up to 14 days: LD50 was determined 301 mg/kg bw. As signs of intoxication tremor, salivation, sedation was noted ; the treated skin showed severe erythema and severe subdermal hemorrhaging.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
301 mg/kg bw
Quality of whole database:
The materials/methods and results are described sufficient for evaluation.

Additional information

ORAL TOXICITY

There is no acute study according to the current OECD test guidelines, but the given information is sufficient to evaluate this endpoint

Following single oral doses to rats the LD50 was determined 207 mg/kg bw. The observed signs of intoxication included  hypoactivity, tremors, lacrimation, dyspnea, hemorrhagic rhinitis, convulsions and prostration (Ind Bio-test Lab Inc 1969).

INHALATION TOXICITY

Following exposure of rats against 710 mg/m³ p-cresol for 1 hour, no rat died and no clinical findings were reported (Ind Bio-test Lab Inc 1969). In Pereima 1975 (cited in WHO1995) the LC50 in rats is reported to be 29 mg/m³ for p-cresol, but exposure time and other relevant data were not available. Clinical signs of toxicity included irritation of mucous membranes, neuromuscular excitation and convulsions; hematuria is reported at very high concentrations.

Overall, the data base on acute inhalation toxicity of p-cresol is very limited and does not allow final conclusion. Nevertheless further testing is not required because p-cresol is evaluated as corrosive and is 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.

DERMAL TOXICITY

There is no acute study according to the current OECD test guidelines, but the given information is sufficient to evaluate this endpoint

To determine LD50 (dermal) value, rabbits received dermal application of 215 -681 mg/kg bw undiluted p-cresol and were observed for clinical signs of toxicity and mortality for up to 14 days: LD50 was calculated to be 301 mg/kg bw. As signs of intoxication tremor, salivation, sedation was noted ; the treated skin showed severe erythema and severe subdermal hemorrhaging (Ind. Bio-test Lab Inc 1969).

Justification for selection of acute toxicity – oral endpoint
The most reliable study was used as key study and for classification.

Justification for selection of acute toxicity – dermal endpoint
The most reliable study was used as key study and for classification.

Justification for classification or non-classification

Under R67/548/EEC(29. ATP) m- and p-cresol as well as o-cresol are classified as toxic in contact with skin and if swallowed: R24/25.

Based on the cited acute data with oral exposure a change in classification and labelling could be considered, but the data base is limited. Therefore the present classification is accepted.

Referring to acute inhalation exposure, the given information is insufficient to evaluate the need for classification because important experimental details are not given. Therefore a classification is not required.

According to Regulation (EC) No. 1272/2008 the substance is allocated to Category 3 for acute toxitity by oral and dermal route; Hazard Communication H301 and H311