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Administrative data

Description of key information

A GLP- and recognized test guideline-compliant study for the acute inhalation toxicity potential of 2-methylpropane-2-thiol is available. For the oral and dermal routes, only preguideline studies are available. Summary results of the key studies are as follows:
Oral LD50 (rat): 4729 mg/kg (Fairchild and Stokinger, 1958)
Dermal LD50 (rat): > 2000 mg/kg (Latven, 1976)
Inhalation LC50 (rat, 4h, whole body): 94.622 mg/L (26643 ppm) (Daly, 1986)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
4 729 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
94 622 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
2 000 mg/kg bw

Additional information

Oral toxicity


Male rats (5/dose; Wistar) were dosed with 2 -methylpropane-2-thiol (pre-guideline study) at doses of 1672, 3344, 6688, and 13,375 mg/kg bw and followed for 14 days. Mortality was 0, 0, 5, and 5 of the 5 animals per group, respectively. No other data (e.g. signs of toxicity) were reported. The LD50 was 4729 mg/kg bw (Fairchild and Stokinger, 1958).


Inhalation toxicity


In an OECD 403 study (Daly, 1986), groups of ten rats (five male and five female) were exposed for four hours to various concentrations of 2 -methylpropane-2 -thiol. The animals were observed immediately prior to exposure, at approximately 15 minute intervals during the first hour of exposure, every half hour during 1 and 2 hours and hourly until the completion of the exposure period. All survivors were observed upon removal from the chamber and hourly for four hours post-exposure. The animals were observed twice daily for mortality and detailed observations were recorded daily through the remainder of the 14 day post-exposure period. Body weights were recorded on Day 1 (prior to exposure), and on Days 2, 3, 5, 8, 11 and 15 (just prior to sacrifice). A gross necropsy was conducted on all animals dying spontaneously during the course of the study and on all animals that survived to study termination. All animals that died did so either during exposure or prior to removal from the chamber (30 minutes after cessation of compound delivery). Lacrimation, labored breathing, reduced activity and prostration were commonly noted during exposure and up to four hours post-exposure. Several instances of ataxia and tremors were also observed. During the recovery period, secretory and respiratory responses were noted initially but signs decreased in incidence and severity as the recovery period progressed. Body weights were significantly decreased in survivors on the day following exposure but, again, there was general recovery by Day 8 post-exposure. A number of animals, which died spontaneously, had red lungs. This is not considered to be unusual in animals which were not exsanguinated prior to postmortem examination. The toxicological significance of this finding, if any, remains undetermined on the basis of gross examination only. Other postmortem findings, observed grossly, occurred sporadically and were not considered to be related to the test article. The LC50s were determined to be 26,643 ppm (94622 mg/m3) for combined sexes, 26,799 ppm for males and 25,643 ppm for females


Male Wistar rats (6/group) and male Swiss mice (10/group) were exposed for four hours to 2 -methylpropane-2-thiol at analytical concentrations of 11520, 15465 and 24495 ppm (Fairchild and Stokinger, 1958). Mortality occurred as follows: 0/6; 0/6 and 4/6 in rats and 0/10, 4/10 and 10/10 in mice, respectively. Maximal sublethal and lethal concentrations induced characteristic symptoms of toxicity, i.e., increased respiration and restlessness, uncoordinated movement and staggering gait, muscular weakness, partial skeletal muscle paralysis beginning in hind limbs, light to severe cyanosis, tolerance of prone position, and mild to heavy sedation. Fatal responses usually followed one of two patterns: (1) animals exposed to maximal lethal concentrations died from respiratory arrest while in or shortly after removal from the chamber, and (2) those animals exposed to minimal lethal concentrations died while in a semiconscious condition of long duration. Animals very often remained in a semi-conscious condition of sedation and lethargy 4 to 6 hours post-exposure before showing signs of recovery. Occasionally a period of deep lethargy of 18 to 28 hours intervened before visible signs of recovery occurred. Irritation to the mucous membranes within approximately 15 minutes after exposure of animals to high concentrations was evidenced by their rubbing of the eyes and nose, eye closure, occasional sneezing, watering of the eyes, and retracting of the head. The 4-hour LC50s were reported to be 4020 ppm in rats and ca. 18500 ppm in mice.


Dermal toxicity


Each of six rabbits (sex/strain not specified) was treated dermally with a single dose of 2000 mg/kg bw of 2 -methylpropane-2 -thiol (pre-guideline study) (Latven, 1976b). Doses were applied to the hair-clipped skin of the trunk under an occluding prefitted sleeve. The sleeves were removed 24 hours later and the animals were then observed for seven days. There were no effects of treatment observed and the LD50 was > 2000 mg/kg bw.

Justification for classification or non-classification

According to REGULATION (EC) No 1272-2008 and the available acute toxicity data:

Acute oral toxicity:

Not classified: rat/LD50 = 4729 mg/kg

Acute inhalation toxicity:

Not classified: rat/4h/LC50 = 94.622 mg/L

Acute dermal toxicity:

Not classified: rabbit/LD50 > 2000 mg/kg