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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Data are available for the read-across substance TAME. One available oral study with rats resulted in a combined LD50 values of 2152 mg/kg. Females appeared to be more sensitive as the LD50 was 1602 mg/kg for females. For males the LD50 was 2417 mg/kg.
The LC50 value via inhalation is over 5400 mg/m3 in rats.
The LD50 value after dermal exposure was higher than 2000 mg/kg bw in rabbits.
In humans, TAME caused slight acute toxic effects at concentrations of 15 (64 mg/m3) and 50 ppm (212 mg/m3).

Key value for chemical safety assessment

Additional information

Based on the considerations described in the document "Read-across substantiation C5-6 branched alkylmethyl-ethers” (incl. the supporting references Tuppurainen et al., 2007 and Niska et al., 2008), it can be concluded that the available information of TAME can be used to predict the acute toxicity of the substance ‘C5-6 branched alkylmethyl-ethers’ with sufficient certainty.

One acute toxicity (GLP-compliant, near-guideline) study regarding TAME with rats (Exxon Biomedical Sciences Inc., 1989) was available for assessment. The groups of 5 male and 5 female Sprague-Dawley rats were exposed by gavage to 2000, 2500 and 3000 mg/kg bw doses of undiluted substance. The combined LD50 value for male and female rats was determined to be 2152 mg/kg bw. Females appeared to be more sensitive than males, as the LD50 for females was 1602 mg/kg bw, compared to the LD50 of 2417 mg/kg bw for males. Clinical observations showed typical signs of sedation and included, for example, ataxia, emaciation, prostration, hypothermia, hypoactivity, dyspnoea, hypopnea, wet and dry rales, clear and red nasal and oral discharge, staining of the fur and piloerection. These observations were most prevalent during day 0 and day 1 in all groups. The animals that died showed abnormalities of the gastro-intestinal tract and the urinary bladder, discoloration of the thymus, lungs and liver and staining of the fur.

One acute inhalation toxicity (GLP-compliant, near-guideline) study with rats exposed to TAME was available for assessment (IIT Research Institute, 1991a). The group of 5 male and 5 female Sprague-Dawley rats was exposed to a TAME vapour concentration of 5400 mg/m3 for 4 hours. None of the animals died. The LC50 value was determined to be > 5400 mg/m3. Regarding clinical observations, rales were seen in all rats immediately following the exposure. The rales were present in 7/10 animals about 2 hours after the exposure, but 3 ¼ hours later all rats appeared normal. Redness around the nose was noticed in 7/10 rats during the study. Necropsy revealed external haemorrhagic lung foci in the lungs in seven rats. However, mostly these foci were comparable in size and number to control rat foci, with the exception of one female rat that had numerous foci and one male that had a diffuse red area on its lungs. Six rats had enlarged mandibular lymph nodes.


One acute dermal toxicity study with rabbits, performed under GLP and according to a procedure comparable with OECD Guideline 402, was available for assessment (IIT Research Institute, 1991b). TAME was applied undiluted at a dose of 2000 mg/kg bw to the shaved backs of five male and five female New Zealand White rabbits. No deaths occurred during the study. The LD50 for TAME was estimated to be greater than 2000 mg/kg bw.

Dermal irritation (i.e. edema and erythema) was observed within the application site of all rabbits after the removal of the wrappings, and eschar formation developed in all rabbits 2 to 7 days later. The scab formation in 3 rabbits sloughed off prematurely probably as a result of grooming, and raw skin was exposed beneath. New and/or repaired skin was observed in six rabbits, while seven rabbits displayed superficial flaking at the application site. None of the rabbits completely recovered from all signs of dermal irritation before the end of the 14-day observation period.

Regarding the observed dermal irritation, the skin irritation study with TAME (see section on skin irritation) is considered more relevant for drawing a conclusion on skin irritation.

In a volunteer study with six humans (men) per group (Pekari et al, 1997b), TAME caused only minor acute effects (exposure concentrations: 15 ppm (60 mg/m3) and 50 ppm (212 mg/m3)). The reporting on the effects is somewhat inconsistent and not very firm conclusions can be drawn from the study. Feeling characterised as heaviness of the head seemed to correlate inversely with increasing TAME concentration. Concentrations up to 50 ppm did not have an effect on reaction time, balance or mood during/after 4-hour exposure. In conclusion, 50 ppm (212 mg/m3)) is considered the NOAEC in this study.

Justification for classification or non-classification

Based on the oral LD50 value for female rats, TAME has to be classified according to Directive 67/48/EEC as Xn – R22 (Harmful if swallowed). In accordance to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, TAME has to be classified for Acute toxicity, Cat. 4 - H302 (Harmful if swallowed). No classification for acute inhalation and dermal toxicity is warranted.

Based on the proposed read-across approach, this classification does also apply for C5-6 branched alkylmethyl-ethers.