Propyloxirane

Endpoint summary

Description of key information

LD50 oral = 1460 mg/kg bw (BASF AG, 1982, OECD401)
LC50 inhalation >10.6 and < 21.3 mg/l (BASF AG, 1990, OECD403)
LD50 dermal >1500 and < 2950 mg/kg bw (Smyth et al, 1962)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 460 mg/kg bw

Additional information

Acute oral toxicity:

The acute oral toxicity of n-pentenoxide-1,2 was assessed according to OECD 401 and GLP. 5 male and female Wistar rats were dosed with 1000, 1470, 2150, 3160 mg/kg bw and by oral gavage and observed for 14 days for mortality, clinical signs and body weight changes. One male rat died at 1000 mg/kg, 1 male and 4 females at 1470 mg/kg, 4 males and 5 females at 2150 mg/kg and all animals died at 3160 mg/kg; animals died within 1 day after application. Clinical signs included dyspnoe, apathy, abnormal position, staggering, atonia, loss of pain reflex, loss of cornea reflex, narcotic condition, scrubby fur, diarrhoea, cyanosis, exsiccosis, bad general condition (15 min-3 days after application). Body weights were as follow: 1000 mg/kg: -mean(males): 225 g (3 days), 241 g (7 days), 279 g (13 days); mean(females): 220 g (3 days), 228 g (7 days), 247 g (13 days); - 1470 mg/kg: - mean(males): 205 g (3 days), 224 g (7 days), 261 g (13 days); mean(females): 211 g (3 days), 231 g (7 days), 244 g (13 days); - 2150 mg/kg: - mean(males): 207 g (3 days), 230 g (7 days), 274 g (13 days).

The statistical evaluation resulted in an LD50 value for Wistar rats (male/female) of 1460 mg/kg bw.

Acute Inhalation toxicity:

The acute inhalation toxicity of n-pentenoxide-1,2 was assessed according to OECD 403 and GLP. 5 male and female Wistar rats were dosed with vapors of 5.3, 10.6, 21.3 mg/L (nominal: 5.6, 11.4, 23.1 mg/L) for 4 h in a whole-body inhalation chamber and observed for 14 days for mortality, clinical signs and body weight changes. None of the animals died at 5.3 mg/L or 10.6 mg/L, but 8 animals (4 male and 4 females) died at 21.3 mg/L either on the day of exposure or one day after exposure. Clinical signs during exposure in all test groups included accelerated respiration, eyelid closure, ruffled fur, wiping of snouts and restlessness. Additionally, abdominal position and staggering gait were observed in high-dosed rats during the exposure. In the low and mid-test groups accelerated respiration and ruffled fur were monitored on the test day; however, animals were free of clinical signs from day 1-day 14. In the high-dosed group, lethality, accelerated respiration, respiratory sounds, reddish nasal discharge (blood test positive), eye discharge, abdominal position, ruffled fur, high-stepping gait, staggering unsteady gait, deteriorated general state and salivation were observed on the day of application; animals having survived the treatment were free of clinical signs from day 1 onwards. The body weight gain of male and female rats in the test groups 1 and 2 and female rats in the test group 3, compared with a historical control collective, was not affected by the substance over the total observation period. The body weight gain of male rats in the high dose test group, compared with a historical control collective, was retarded in the first week of the observation period and adjusted to normal in the second week of the observation period. Gross pathology of the dead animals from the high does group included general congestion as well as focal hyperemia with edema and areas with emphysema in the lung, observation of slight hydrothorax. No pathological findings were noted in all animals having survived the treatment.

The statistical evaluation resulted in an LC50 for Wistar rats (male/female) between 10.6 and 21.3 mg/L.

Acute dermal Toxicity:

Justification for read-across to 1,2 -Butenoxide:

For the determination of the acute dermal toxicity of n-Pentenoxide-1,2, a read-across was performed to 1,2-Butenoxide, another member of the epoxide family. The only structural difference between n-Pentenoxid-1,2 and 1,2-Butenoxide is the presence of an additional CH2 -group in n-Pentenoxide-1,2. The chemical characteristics between these two substances are quite similar, with 1,2 -Butenoxide being more soluble in water (86.6 g/L vs 23 g/L water solubility) and less lipophilic (log Pow=0.68 vs 1.29) and exhibiting a higher vapor pressure (227 hPa vs 70 hPa) as compared with n-Pentenoxide-1,2. It has been shown that the toxicities of epoxides decrease from ethylenoxide to propylenoxide to 1,2-Butenoxide, suggesting that the toxicity of this reactive group of epoxide chemicals decreases with increasing length of the carbon backbone (Fox et al, 1983; NTP report No 267, 1985). In line with this assumption, the oral LD50 of 1,2-Butenoxide is smaller (900 mg/kg) as compared with n-Pentenoxide-1,2, further supporting the validity of a read-across from n-Pentenoxide-1,2 to 1,2-Butenoxide, taking into account that this will represent a worst case scenario.

Smyth et al (1962) showed that the LD50 for dermal acute toxicity of 1,2 -Butenoxid is between 1500 and 2950 mg/kg bw. Penetration of rabbit skin is estimated by a technique closely akin to the one-day cuff method of Draize and associates, using groups of four male albino New Zealand rabbits weighing 2.5 to 3.5 kg. The fur is removed from the entire trunk by clipping, and the dose is retained beneath an impervious plastic film (occlusive dressing). Dosages greater than 20 ml/kg cannot be retained in contact with the skin. The animals were immobilized during the 24-hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14-day observation period. The study does neither state any precise numbers of animals that died nor mentiones the doses tested, but only states that the LD50 is between 1500 and 2950 mg/kg bw. Even though the toxicity of epoxydes was reported to decrease with increasing carbon backbone length, this LD50 will also be applied fpr the risk assessment of n-Pentenoxide-1,2, which hence decribes a worst case scenario.

Justification for classification or non-classification

According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) the test substance should be labeled with Xn; R20/21/22.

According to Regulation (EC) No 1272/2008 (CLP), the test item is classified as acute oral, dermal and inhalation (vapor) category 4 and labelled with "Warning" and H302/312/332.