p-cresol

Endpoint summary

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 a 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 or test system 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:

other: Onset in all animals within the first 4 hours post dosing: hypoactivity, tremors, lacrimation, dyspnea, hemorrhagic rhinitis, convulsions, prostration, recovery occurred in all survivors.

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 or test system 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:

other: signs of intoxication from 4-12 hrs post appl.: tremor, salivation sedation , recovery occurred within 3 days post application

Gross pathology:

gross autopsy: survivors: no significant findings; decedents: inflammation of kidneys

Other findings:

dermal irritation: severe subdermal hemorrhaging, severe erythema

Doses and 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 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

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