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Administrative data

Description of key information

Most critical values of cresols:
oral: LD50 rat 121mg/kg bw (o-cresol)
dermal: LD50 rat 301mg/kg bw (p-cresol)
inhalation: LC50 rat >710mg/m³ (m-cresol and p-cresol)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
121 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
710 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
301 mg/kg bw

Additional information

Acute oral toxicity:

The most critical value for cresols was reported in the study performed witho-cresol where the oral LD50of undiluted o-cresol in rats was determined to be 121 mg/kg bw. Oral gavage studies withm-cresol andp-cresolconducted in rats returned LD50values of 242 and 207 mg/kg bw, respectively. In all 3 studies mortalities occurred in all except the low dose groups. The observed signs of intoxication for all cresols included hypoactivity, tremors, lacrimation, dyspnoea, hemorrhagic rhinitis, convulsions and prostration observed within 4 hours post dosing. (Ind. Bio-test Lab Inc 1969).

In a fixed dose acute oral toxicity gavage study conducted with am+p-cresol mix, the acute oral LD50was estimated to be in the range of 300 – 2000 mg/kg bw (Bradshaw, 2015).

Acute inhalation toxicity:

An acute inhalation study was performed similar to OECD 403 withp-cresol (Ind Bio-test Lab Inc 1969). Six rats were exposed to 0.71 mg/L for 1 hr at room temperature and observed for clinical signs or mortality up to 14 days post exposure. Gross necropsy was performed at the end of the observation period. The same study was performed withm-cresol where additional information about the airflow of 10.0 L/minute was reported. The exposure of male rats for 1 hour to 0.71 mg/L m-cresol orp-cresol led to no mortalities or any clinical signs. These studies where chosen for the most critical LC50of the cresols because of their higher reliability in comparison to the other performed study witho-cresol. Six male rats were exposed to 1.22 mgo-cresol/L and observations for clinical signs, mortality and gross autopsy were reported. Generalized inactivity and lacrimation were observed at the first 15-30 minutes of treatment with recovery at treatment day.

In an acute toxic class inhalation study with a m+p-cresol mix, the acute inhalation LC50was estimated to be 1.18 mg/L (Griffiths, 2015).

Acute dermal toxicity:

The LD50ofp-cresol for acute dermal exposure was the most critical of cresols with 301 mg/kg bw. The other cresols revealed LD50of 1380 mg/kg bw (o-cresol) and 2050 mg/kg bw (m-cresol). All studies were performed by Bio-test Lab Inc (1969) on 5 rabbits that received 4 doses of the cresols respectively. The animals were observed for 14 days post exposure and mortality and clinical signs were reported. Mortalities occurred in all dose groups between 215 mg/kg bw (1 out of 5) and 3160 mg/kg bw (5/5). Clinical signs included hypoactivity, tremor, convulsion, salivation, dyspnoea, prostration and additionally the treated skin showed severe erythema and burns in the high dose groups.

In a standard acute class acute dermal atoxicity study conducted with with a mixedm+p-cresol blend, 1 male and 1 female rat had undiluted test aricle applied at 2000 mg/kg bw to the dorsal surface under a semi-occlusive dressing. The intention was that the test article would be applied for 24 hours, however due to the sevierity of clinical signs of toxicity animals were killedin extremis(Bradshaw, 2015).

Justification for classification or non-classification

Cresols have to be classified according to:

CLP: oral category 3, H301: Toxic if swallowed; dermal category 3, H311: Toxic in contact with skin; inhalation category 4, H322: Harmful if inhaled