1,5,10-trimethylcyclododeca-1,5,9-triene, epoxidised

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with 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 will be lower than dermal exposure because the registered substance has a very low vapour pressure (0.161 Pa at 20°C) and a low freezing point (< -20°C), so the potential to generate vapor is low. Nonetheless, considering the use of the substance, exposure to mist can occur. However, based on the absence of acute toxicity by oral route, no mortality is anticipated during the exposure to mist. Hence, dermal exposure is the more likely route of exposure during the manufacture and the use of the substance leading to the low penetration of the substance based on its partition coefficient (Log Kow = 5.05 at 30°C).

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Acute toxicity: oral: LD50 > 5000 mg/kg bw (OECD 423 in rats, GLP, rel.1, K)

Acute toxicity: dermal: LD50 expected to be > 5000 mg/kg bw (non-OECD, non-GLP, rel.4, S)

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The key study was a GLP study conducted in compliance with OECD Guideline No. 423 without any deviation. This study was considered sufficiently robust to cover this endpoint. The other study performed on the registered substance in rats was non-GLP and was of poor quality (Klimish score = 4) but supports the results of the key study.

Endpoint conclusion:

no study available

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available study was not conducted according to accepted test guideline and it is of poor quality (Klimisch score = 4). It is not considered sufficient in its own for acute dermal toxicity endpoint but was used together with the acute oral toxicity study (Klimisch score = 1) to conclude on the dermal hazard potential.

Acute toxicity: oral

A key study was identified (Safepharm, 2006, rel.1). In this limit acute oral toxicity study, which was performed according to OECD Guideline No. 423 and in compliance with GLP, female Sprague Dawley CD rats was treated with the test material at a dose level of 2000 mg/kg bw.The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations. No mortality was observed. Signs of systemic toxicity noted during the study were hunched posture, lethargy, ataxia, increased salivation, decreased respiratory rate and noisy respiration. Animals appeared normal two, three or four days after dosing. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

This study gave an estimated oral LD50 (rats) > 5000 mg/kg bw.

In an other acute oral toxicity study (Industrial Bio-Test Laboratories, 1973, rel.4), groups of Charles River strain (COBS) rats (2/sex/dose) were administered a single oral dose of test material at 50% in corn oil at doses of 6834, 10250, 15380 and 23070 mg/kg bw by gavage. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

One female died at 15380 mg/kg bw of test item 50%. One male and two females died at 23070 mg/kg bw of test item 50%. Hypoactivity, ruffed fur and labored breathing were observed in all treated groups. Muscular weakness was observed at 10250 mg/kg bw, 15380 mg/kg bw and 23070 mg/kg bw of test item 50%. Salivation was observed at 15380 mg/kg bw and at 23070 mg/kg bw of test item 50%. Convulsions were observed at 23070 mg/kg bw of test item 50%. All animals showed expected bodyweight gains over the 14 day study period. Necropsy examinations of the animals that died revealed gastroenteritis. No gross pathologic alterations were noted among the animals sacrificed at 14 days.

This study gave a combined oral LD50 (rats) > 9415 mg/kg bw.

Acute toxicity: dermal

In an acute dermal toxicity study (Industrial Bio-Test Laboratories, 1973, rem.4), a group of rabbits (2/sex) were given a single dermal application of test substance at 50% at the dose of 2000 mg/kg bw under occlusive dressing for 24 hours. Animals were observed for toxicity, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.No mortality or clinical signs were observed. Skin reactions observed at 24 h were pale red to red, well-defined erythema and barely perceptible edema. Severe desquamation was observed at 7and 14 days. No other gross pathologic alterations were observed.

This study gave a dermal median LD50 rabbit (50%) > 2000 mg/kg bw, thus dermal median LD50 rabbit (100%) > 1000 mg/kg bw. This study cannot be used alone for classification since the substance was tested diluted and not up to the limit dose relevant for classification.

However, according to ECHA R7a guidance (2016), further study need not to be conducted because the substance does not meet the criteria for classification for acute toxicity or STOT-SE by the oral route and no systemic toxicity was observed in the existing acute dermal toxicity study up to 1000 mg/kg bw, nor in the in the GPMT study. Thus, the dermal LD50 is expected to be higher than 5000 mg/kg bw.

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Under the test conditions, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the estimated oral LD50 is higher than 5000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available data, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the oral LD50 is expected to be greater than 5000 mg/kg bw.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study. The effects observed in the acute oral toxicity studies are considered to be linked to the stress produced by gavage administration at high doses.

Specific target organ toxicity: single exposure (Dermal):

Based on available data via both the oral and dermal route, the classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single dermal exposure Category 1 or 2 are not considered to be met. No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute dermal toxicity study, nor in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.