4-chloro-o-cresol

Endpoint summary

Description of key information

4-Chloro-o-cresol is classified as toxic by inhalation. 

Additional information

A number of reports on the toxicity of 4 -chloro-o-cresol were submitted for review by the Danish Authorities under the High Production Volume programme (HPV) and in all cases the Scantox studies are considered to be the most reliable after peer review. No new studies are available for inclusion, therefore the classification with respect to acute toxicity is based on previously reviewed studies.

In respect of acute oral toxicity, studies by Hazleton Laboratory (1977) and BASF (1978) were unavailable for review by the Danish EPA but the results were in accordance with the Scantox study, the robust summary of which is included in this document.

A study by Hattula et al. (1979) was not cited to be guideline and gave a LD50 of 1,190 mg/kg and as no other study corroborates this value the result was not included in the calculation of the overall LD₅₀. Studies by Schrotter (1971) and at Huntingdon (1977) were performed on mice. The Schrotter study contained very limited experimental detail and as a result could not be included. Range finding studies at Huntingdon, where mice died consistently at lower doses than in any other studies (i.e. <576mg/kg) indicated that the vehicle may play an important role in the absorption after oral administration and as with the Schrotter study was not included in the overall LD₅₀ calculations.

Table 1 shows a summary of all results cited in the Danish Review document for reference.

Table 1. Summary of Oral Toxicity Results

Species	Application	Dose, mg/kg	Effect	Literature
Rat	oral	3195	LD50	Scantox, 1982b
Rat	oral	2,700	LD50	BASF AG, 1978*
Rat	oral	2,650	LD50	Hazleton, 1977
Rat	oral	1,190	LD50	Hattula et al,1979
Mice	oral	1,330	LD50	Schrotter et al, 1977
Mice	oral	<576	LD50	Huntingdon, 1997

*Unpublished results cited in BUA report,1994

Considering the reliablity of the results tabulated above the  LD_{50 oral,rat} is concluded to be 2,650 -3,195 mg/kg based on studies by Scantox, Hazleton and BASF.

In respect of toxicity via the dermal route, one study in addition to the Scantox study, was cited in the Danish EPA risk assessment. A study performed by Hazleton Laboratories (1977) was unpublished and cited in the BUA report (1994). This study was pre-guideline and not available for review, hence was unable to be considered. The Scantox study was therefore the only reliable study available.

In respect of toxicity by inhalation, one study in addition to the Scantox study was cited in the Danish EPA risk assessment. The study performed by Hazleton Laboratorites (1977) cited in the BUA was pre-guideline and the study was not available for review, hence the guideline Scantox study was the only reliable study available.

In summary the Scantox reports (1982b, c and 1983a) are considered to be the most reliable. The additional studies cited are either poorly reported, unavailable or not to guidelines.

The overall conclusion for acute toxicity is:

LD50 oral,rat       = 2650- 3195 mg/kg / bw

LD50 inh,rat       = 0.9mg/L (as an alcohol aerosol) (900mg/m3)

LD50 dermal, rat = 2,240mg/kg/bw

Justification for classification or non-classification

Under the DSD regulations the LD50 inh, rat endpoint of 0.9mg/L falls within the range 0.25 - <= 1.0g/L, this results in a R23 classification. Under the GHS regulations the endpoint falls in the range >0.5 - <= 1.0 mg/L resulting in Acute Toxicity Category 3 classification.

Based on the observations seen in the inhalation study; specific target organ toxicity is also required under GHS regulations, STOT single exposure Category 3.

The toxicity end points for dermal and oral routes of exposure are above the 2000mg/kg/bw threshold for classification under both the GHS and DSD regulations; therefore no classification relating to oral or dermal toxicity is required.  As no new studies are available for inclusion, the classification is based on the existing peer reviewed document (European Risk Assessment for 4 -Chloro-o-cresol, Danish EPA, 2002).