Reaction mass of 1-methyl-4-(1-methylethylidene)cyclohexyl acetate and p-menth-1-en-8-yl acetate

Endpoint summary

Description of key information

Acute oral toxicity: LD50 is 5075 mg/kg bw (95% CI = 4160-6190) based on read across from alpha-Terpinyl Acetate (being the main constituent of Terpinyl Acetate multi) which was tested in an OECD TG 401.

Acute dermal toxicity: expected to be >=5075 mg/kg bw, based on the information from the acute oral study.

Acute inhalation toxicity: 26390 based on route to route extrapolation from the oral route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Publication published in a peer reviewed journal with some limitations in design and/or reporting but sufficiently adequate to cover this endpoint.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

First the executive summary of the source is presented and thereafter the read across justification.

Acute toxicity oral of alpha-Terpinyl Acetate:

In an acute oral toxicity study groups of 10 Osborn-Mendal rats were exposed through oral intubation to alpha-Terpinyl Acetate. All animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal and showed weight gain. Animals exposed to alpha-Terpinyl Acetate showed depression, scrawny appearance, and porphyrin-like deposits around eyes and nose. A LD50 of 5075 mg/kg bw (95% CI = 4160-6190) was determined.

Acute toxicity dermal:

The study is scientifically unjustified because the acute dermal toxicity can be derived from the acute oral toxicity using route to route extrapolation. Based on the toxico-kinetic information (see IUCLID section 7.1) the dermal availability is not expected to exceed the oral availability. Therefore the LD50 via the dermal route can be estimated to be similar to the oral LD50, because we assume 100% absorption via both routes. This results in an LD50 of 5075 mg/kg bw for the dermal route. Based on this information it can be concluded that the performance of an acute dermal toxicity study will not add useful information on the hazard, the classification and labelling and the risk characterisation of Terpinyl Acetate multi for workers and consumers. The information is thought to be sufficient to show that testing on vertebrate animals for acute dermal toxicity can be omitted, in accordance with Annex XI (1.2).

Acute toxicity inhalation of alpha-Terpinyl Acetate:

No data on acute inhalation toxicity of Terpinyl Acetate multi are available. According to Column 2 of REACH Annex VIII, “in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure.” In the present case, inhalation exposure is not likely because Terpinyl Acetate multi has a low vapour pressure. Furthermore, as acute toxicity information of both the oral and the dermal route of exposure is available, testing for acute inhalation toxicity is not necessary. However, the acute inhalation toxicity for Terpinyl Acetate multi can be derived using data on the acute oral toxicity using the following methodology presented in ECHAs guidance on CLP: 1 mg/kg bw is 0.0052 mg/l. The LC50 is 5075 mg/kg bw and therefore the LC50 would result in 26390 mg/m3, using 100% absorption for both routes. The saturated vapour pressure is 282 mg/m3 and therefore the LC50 for vapour exposure cannot be reached and therefore there is no acute inhalation toxicity.

Read across justification for Terpinyl Acetate multi from Terpinyl acetate alpha for acute oral toxicity:

For assessing the acute oral toxicity of Terpinyl Acetate multi the information from alpha-Terpinyl Acetate will be used for read across. In the toxico-kinetic section the constituents of Terpinyl Acetate multi and of alpha-Terpinyl Acetate are presented. This shows that alpha-Terpinyl Acetate is the main constituent of Terpinyl Acetate multi. The acute oral toxicity for Terpinyl Acetate multi is covered for > 80% % when using the data of alpha-Terpinyl Acetate, because this alpha component also contains the other constituents of the multi but in slightly lower percentages. It can also be seen that all constituents of Terpinyl Acetate multi have a similar backbone, which is the cyclohexyl ring. The attached methyl groups are in all cases para-positioned. There are two functional groups. The first one is the tertiary alcohol, which is not reactive because no additional reactive groups are adjacent to this alcohol. The second functional group is the double bond at the para–position but can be inside or outside the cyclohexyl ring, depending on the constituent. These differences are thought to be of minor importance for the acute oral toxicity and therefore the LD50 value of alpha-Terpinyl Acetate can be used for read across to Terpinyl Acetate multi, resulting in an LD50 > 5000 mg/kg bw.

Justification for classification or non-classification

The substance does not need to be classified and labelled in accordance with EU CLP (EC 1272/2008 and its amendments based on oral LD50 > 5000 mg/kg bw in rats, a predicted dermal LD50 > 5000 mg/kg bw and the calculated inhalation LC50 of 26390 mg/m3 being far above its saturated vapour pressure.