Allyl 2,3-epoxypropyl ether

Endpoint summary

Description of key information

Allyl Glycidyl Ether (AGE) is harmful if swallowed and toxic if inhaled. AGE may be harmful in contact with skin according to GHS-UN (Cat 5) standards.
LD50 Oral (rat) = 830 mg/kg bw (male) and 1164 mg/kg bw (female)
LD50 Dermal = 2550 mg/kg bw (rat) 
LC50 Inhalation-vapor (rat- 4h) = 2.56mg/l (male)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

830 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

2 560 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 550 mg/kg bw

Additional information

Oral exposure route:

Two studies were considered as key. In one study (Hine et al. 1956), male rats (n = 6) were dosed at 1300, 1600, 1900 and 2300 mg/kg bw allyl glycidyl ether (AGE) by intragastric intubation once. Mortality was observed at 1600, 1900 and 2300 mg/kg bw: 3/6, 5/6 and 5/6, respectively, and LD50 was established to be 1600 mg/kg bw. Treated rats showed signs of distress such as slight lacrimation, mussed fur, restlessness, slight unsteadiness, slight to moderate depression and dyspnea. Most survivors recovered overnight. Lethargy or coma was observed prior to death. At necropsy, rats that died showed diffuse inflammation of the lungs, slight to moderate irritation of the gastroenteric tract with fluid distention and petechial haemorrhages in the stomach. Spleen and kidneys were pale and discolored. Rats at scheduled sacrifice showed hypotonicity of the enteric tract and extensive adhesions of the stomach wall to adjacent tissues. One animal showed focal areas of necrosis in the liver during macroscopically examination. In the other key study (DOW 1978) performed similar to OECD guideline 401, six groups of rats were dosed by gavage at dose levels of 500, 1000, 1120, 1260, 1580 and 2000 mg/kg bw. Mortality occurred at 1000 mg/kg bw onwards, and LD50 was considered to be 830 mg/kg bw (females) and 1164 mg/kg bw (males). Prior to death, both male and female rats were lethargic, had piloerection, and had diarrhea. Gross pathological examination of male and female rats of the 500 mg/kg bw dose group (the least amount dosed) at 14 days after dosing revealed irritation of the nonglandular portion of the stomach, including hyperkeratosis, erosion, and ulcerations.

These findings were supported by further acute oral studies in which LD50 values of ca. 1746 mg/kg bw in males and female rats (BASFAG XVIII 219, 1968), and 260-340 mg/kg bw in male mice (Hine et al. 1956) were reported.

Taking all the presented data into consideration, AGE is classified as R22 according to EU standards and in Cat 4 according to GHS and CLP standards.

 

Inhalation exposure route:

Two studies were considered as key. In one study (DOW 1978), male rats (n=6) per dose group were exposed to the nominal vapor concentrations of 0.47, 1.18, 1.42, 1.78, 2.37, 3.32, 5.57 and 12.31 mg/l for 7 h. Mortalities occurred at 1.42 mg/l onwards and the LC50 was established to be 1.46 mg/l (ca. 2.56 mg/l for 4 h exposure). During exposure to the top 3 exposed groups, the rats showed gasping and had exudates around the nose and mouth. Slight nasal irritation and slight gasping were observed in rats of the 0.47 mg/l group during exposure. These signs of toxicity occurred with increasing severity as the exposure level increased. In the other key study (Hine et al. 1956), groups of 6 male rats were exposed to the vapor generated from the test substance at the nominal concentrations of 1.4, 2.1, 3.12 and 4.66 mg/l for 8 hours.Mortality was observed at 1.4, 2.1, 3.12 and 4.66 mg/l and LC50 was established to be between 3.12 and 4.66 mg/l (6.24 - 9.32 mg/l for 4 h exposure). Considerable lacrimation, nasal and salivary discharge, dyspnea, gasping and corneal opacity were noted. Rats dying during the study showed moderate to severe diffuse inflammation and hemorrhage of the lungs, pleural effusion, emphysema, bronchophenumonia, severe gaseous distension of the G.I. tract, pale and mottled liver and kidneys, engorged and enlarged adrenals as well as hypertrophy of the spleen. Rats from scheduled sacrifice showed slight diffuse inflammation of the lungs, emphysema, bronchopneumonia and mottled discoloured kidneys. Microscopically, 2 rats showed pneumonia.

The above findings were supported by another study in male mice where LC50 was reported to be 1.26 mg/l (Hine et al. 1956).

Taking all the presented data into consideration (the lowest LD50 value), AGE should be classified as R20 according to EU standards and in Cat 3 according to GHS / CLP standards.

 

Dermal exposure route:

In the key study (Hine et al, 1956), three male rabbits were exposed to 730, 1450, 2900 and 5800 mg/kg bw AGE by skin application under occlusive conditions for 7 h. Mortality was observed at 2900 and 5800 mg/kg bw, 2/3 and 3/3, respectively, and LD50 was established to be 2550 mg/kg bw. Mortality occurred within 7 hours after prior observed increasing depression. At necropsy constricted kidneys and spleens were observed. Microscopically, no abnormalities were noted. In another study, 4 groups of 4 rabbits each were subjected to an acute percutaneous absorption test resulting in mortality of 0/4, 1/4, 3/4 and 4/4 in the 252, 500, 1000 and 2000 mg/kg bw dose groups, respectively. The volume of administration, type of coverage and duration of exposure were not mentioned. Topical responses observed when the cuffs were removed included an application site which was purple in color, had moderate to severe swelling, and was necrotic. Prior to death, rabbits were lethargic and had labored breathing. Surviving rabbits behaved in a normal fashion, but had hard, leathery patches over the entire application site. The mortalities and necrosis of the skin observed in rabbits might be due to very longer exposure period or type of coverage used or other reasons, which are not documented in the present study. Due to lack of documentation (reliability 4), the results can not be used for assessment.

Based on the results, AGE is classified in Cat 5 according to GHS (UN) standards. No classification is required according to EU standards.

Justification for classification or non-classification

EU classification according to Annex I of Directive 67/548/EEC: Xn, R20/22

CLP Regulation (EC No 1272/2008)

- Oral route: Acute Category 4

- Dermal route: Not classified

- Inhalation route (vapour): Acute Category 3