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Description of key information

A LD50 of 5075 mg/kg bw (95% CI = 4160-6190) was obtained in the acute oral toxicity study with rats. A LC50 value of 30450 mg/m3 was calculated for acute inhalation toxicity being above the saturated vapour pressure of 281 mg/m3.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Publication published in a peer reviewed journal with limitations in design and/or reporting but otherwise adequate for assessment.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Fasting period before study: approximately 18
- Housing: Cages
- Diet: ad libitum
- Water: ad libitum



Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All doses were given by intubation.
Doses:
Not reported
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
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. The usual observation period was 2 weeks; in a few cases, where no acute toxic signs were seen, the animals were observed for only one week.
Statistics:
LD50's were computed by the method of Litchfield & Wilcoxon (1949).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 075 mg/kg bw
Based on:
test mat.
95% CL:
4 160 - 6 190
Mortality:
Death Time: 4 hr - 5 days
Clinical signs:
Depression, scrawny appearance, porphyrin-like deposits around eyes and nose
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A LD50 of 5075 mg/kg bw was obtained in the acute oral toxicity study with rats.
Executive summary:

In an acute oral toxicity study, performed similar to OECD Guideline 401, groups of 10 Osborn-Mendal rats were exposed through oral intubation to the test substance. 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 terpinyl acetate alpha 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.

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
Quality of whole database:
The route to route extrapolation from the acute oral toxicity is sufficiently adequate to cover this endpoint.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The route to route extrapolation from the acute oral toxicity is sufficiently adequate to cover this endpoint.

Additional information

Acute toxicity oral:

In an acute oral toxicity study, performed similar to OECD Guideline 401, groups of 10 Osborn-Mendal rats were exposed through oral intubation to the test substance. 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 50% absorption via both routes. 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 alpha-Terpinyl Acetate 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:

No data on acute inhalation toxicity of alpha-Terpinyl Acetate 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 alpha-Terpinyl Acetate has a low vapour pressure. Furthermore, as acute toxicity information on both the oral and the dermal route of exposure is available, testing for acute inhalation toxicity is not necessary. In addition, the acute inhalation toxicity for alpha-Terpinyl Acetate can be derived using data on the acute oral toxicity using the following methodology. The oral LD50 of alpha-Terpinyl Acetate is 5075 mg/kg bw. The 5075 mg/kg bw can be converted to 304500 mg/per person. An inhalation volume of one person during 4 h (standard exposure time in OECD TG for acute inhalation toxicity) is 5m3 (assuming 10m3/8h for workers). This means that the LC50 concentration in 1m3 and 4 hours exposure is 60900 mg/m3.Taking into account that the absorption during inhalation route can be twice as high as during oral absorption the LC50 for inhalation would become 30450 mg/m3. The maximum saturated vapour pressure (SVP) for this substance in mg/m3 is (3.515 Pa x 196 MW (mg/Mol)) /(8.3 (R, gas constant) x 296°K) = 281 mg/m3.The LC50 value of 30450 mg/m3 cannot be reached because of the SVP of alpha-Terpinyl Acetate of 281 mg/m3. Though no correction has been done for rat versus human inhalation, the calculation clearly shows that there is no acute inhalation toxicity because the calculated LC50 = 30450 mg/m3, while the SVP is 281 mg/m3.


Justification for selection of acute toxicity – oral endpoint
One acute oral toxicity study is available performed with alpha-Terpinyl Acetate, which is sufficiently reliable.

Justification for selection of acute toxicity – inhalation endpoint
The information is derived from the acute oral toxicity results using route to route extrapolation and is sufficiently reliable.

Justification for selection of acute toxicity – dermal endpoint
The information is derived from the acute oral toxicity results using route to route extrapolation and is sufficiently reliable.

Justification for classification or non-classification

Alpha-Terpinyl Acetate does not need to be classified and labelled in accordance with EU Directive 67/548 and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 for acute oral, dermal, and inhalation toxicity based on the oral LD50 > 5000 mg/kg bw in rats, a predicted dermal LD50 of > 5000 mg/kg bw and the calculated inhalation LC50 of 30450 mg/m3 being far above its saturated vapour pressure.