3,3,5-trimethylcyclohexan-1-one

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

Additional information - workers

The lead registration dossier is for a substance manufactured at > 100 t/a for non-intermediate uses. However, the endpoints 7.5 and 7.8 can be waived as the conditions of Annex XI.3.2 will be fulfilled by either:

a) 3,3,5-trimethylcyclohexan-1-one (TMCone) is manufactured and used under strictly controlled conditions (SCC) according to Article 18.4 (Annex XI.3.2.); or

b) in exceptional cases where strictly controlled conditions deviate from the current ECHA definition it will be shown that “no significant exposure occurs in all scenarios of the manufacture and all identified uses as referred to in Annex VI section 3.5”. The lack of significant exposure is verified by workplace measurements. Due to the fact that no long-term toxicity data are available a reliable DNEL as indicated in Annex XI.3.2.(a)(ii) cannot be derived. Therefore, the absence of a significant exposure is initially based on the concept of the Threshold of Toxicological Concern (TCC). Based on its structure 3,3,5-trimethylcyclohexan-1-one is assigned Cramer Class II. The TTC value for Cramer Class II substances is 540 µg/person/day derived by Munro et al (1996). EFSAs Scientific Committee noted 2012 that the TTC value for Cramer Class II substances derived by Munro et al. in 1996 was based on toxicological data on very few substances. Databases compiled subsequently have similarly found few chemicals classifiable as Cramer Class II, apart from flavoring substances. Thus, the Scientific Committee considers that the TTC value of 540 µg/person/d for Cramer Class II is not well supported by the presently available databases and therefore concludes that consideration should be given to treating substances that would be classified in Cramer Class II under the Cramer decision tree as if they were Cramer Class III substances. Accordingly a TTC of 90 µg/person/d (1.5 µg/kg bw/day) would be assigned as safe dose for a Cramer class II substance. However, classifying TMCone as Cramer Class III substance is considered over-conservative.

In general, 3,3,5-trimethylcyclohexan-1-one is manufactured and used under strictly controlled conditions in accordance with REACH regulation Article 18(4). At present, the filling of containers does not fully meet the requirement of a rigorous containment. However, the vapor pressure of TMCone is 60 Pa at 20°C thus it is expected to evaporate to some extent. The use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur.

To confirm this, workplace measurements have been performed in June 2012. The filling procedure of a standard container was monitored. The measuring instrument was positioned at the workers breathing zone during all steps of the procedure. A concurrent positive control was done by measuring the TMCone concentration at the headspace of a full container. A full work cycle was 5 to 6 minutes. At all time points the TMCone concentration was below the limit of detection of 1.42 ppm.

Even though TMCone has not been detected in ambient air it was technically not feasible to exclude an exposure below 1.42 ppm (limit of detection). However, a potential exposure can be assessed based on the exposure scenario developed in Chapter 9 (9.2.2.3).

Assuming an exposure period of 6 min (= 0,125 m3) and a maximum concentration of 0.204 mg/m3 (Table 54) the inhaled dose would not exceed 0.026 mg/person/container. As not more than one container is discharged per day, the exposure does not exceed 0.026 mg/person/day. This exposure occurs about 10 times per year, thus it is not considered to be chronic.

An exposure of 0.026 mg/person/d is well below the TTC of 540 µg/person/d for a Cramer Class II substance and even below the TTC of 90 µg/person/d for a Cramer Class III substance. Thus, a potential lifelong daily exposure at this concentration would be considered negligible.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Additional information - General Population

industrial use only