Reaction mass of 2-methoxy-2-methylbutane and 4-methoxypent-2-ene

Endpoint summary

Description of key information

One available oral study with rats resulted in a combined LD50 value 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

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 152 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

5 400 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

One acute toxicity (GLP-compliant, near-guideline) study 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 undiluted substance at 2000, 2500 and 3000 mg/kg bw. 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). A single group of 5 male and 5 female Sprague-Dawley rats was exposed to TAME vapour at 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. The test site was covered with an occlusive dressing. 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, given the occluded conditions used in this test, 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. Feelings 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 with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the substance has to be classified for Acute toxicity, Cat. 4 - H302 (Harmful if swallowed). No classification for acute inhalation and dermal toxicity is warranted.