Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: 
Key study -mixed ethylphenols. York, 2005. KL.1. LD50 980.62mg/kg; NOEL 175mg/kg;
Supporting study: mixed xylenols. York, 2005. KL.1 LD50 980.62mg/kg; NOEL 175mg/kg;
Supporting study: m-cresol. IBTL, 1969. KL.3. NOEL not identified. LOAEL 147mg/kg;
Supporting study: o-cresol. IBTL, 1969. KL.3. NOEL not identified. LD50 121mg/kg; LOAEL 68mg/kg;
Supporting study: p-cresol. IBTL, 1969. KL.3. NOEL not identified. LD50 207mg/kg; LOAEL 100mg/kg;
Acute inhalation toxicity:
No key or supporting studies identified;
Acute dermal toxicity:
No key or supporting studies identified;

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
discriminating dose
175 mg/kg bw

Additional information

Acute oral toxicity

The key study on ethyl phenols and the supporting study on xylenols both confirm the LD50 at 980.62 mg/kg and the NOEL at 175 mg/kg. These studies performed were available to review and the robustness of the NOEL confirmed.

 

For all three cresol isomers the data summaried was already provided and therefore reports were not available to enable complete evaluation and suitability for the LD50 / LOAEL values set. These studies are in excess of 40 years old and consequently not conducted to any guideline, with data absent. The LOAEL determined have been dictated by the dose levels set, with clinical signs of toxicity observed at the LOAEL similar to that observed at higher doses in both the guideline compliant studies on ethylphenols and xylenols. It is likely that the true NOEL for the cresols if conducted to modern day guideline compliant protocol would be similar to that observed for the xylenols and ethylphenols.

 

Furthermore, it is important to note that Cresols will only constitute <25% of xylenol / ethylphenol mixture and so would only affect NOAEL / NOEL of mixtures in which they were present if they were significantly more toxic than xylenol /ethylphenol isomers.

 

Acute dermal toxicity

The key study available on 3,5 xylenol confirms an LD50 value in excess of 2400 mg/kg for a study conducted nearly 30 years ago. This value is reinforced by similar LD50 vaules ranging from 2000 to 2325 mg/kg for the 2,4 and 2,6 isomers. Whilst the cresols data reports are in excess of 40 years old, the LD50 values reported for m and p cresol (2050 and 138 mg/kg, respectively) reinforce the data obtained for the xylenols. Based on structural similarities, one would assume that the ethyl phenols would give similar values. It should be noted that the LD50 value for o-cresol was 301 mg/kg. As o-cresol is only a very small component of the mixture (if present) is unlikely to affect the overall NOAEL.

 

Effects reported (with the exclusion of 3,5 xylenol where no clinical signs of toxicity or skin reactions were noted) clinical signs were attributed to local irritant effects. With transient signs of increased salivation and hypoactivity.

 

The available acute dermal toxicity data is limited, but consistently shows that local irritant effects are the endpoint of concern which persisted without resolution.

 

Currently under EU Directive 67/548 EEC both xylenols and cresols are classified as corrosive, with the R phrases of R24 'toxic in contact with skin and R34 'cause burns' applied. Therefore in accordance with REACH R7.A guidance no further testing is warranted. DNEL setting for the dermal route will be extrapolated form the oral route. The dermal studies reported are limited in respect of the data available; therefore route to route extrapolation has been undertaken from the oral data inorder to derive a acute dermal systemic DNEL.

 

Acute inhalation toxicity

No key or supporting studies were identified. What information is available reports LC50 values 0.29 mg/L through to 30 mg/m3 where no mortality was observed. The exposure duration is either 1 hour or unknown and therefore not compliant with the required 4hr exposure.

Justification for classification or non-classification