(E)-3-formylbut-2-enyl acetate

Endpoint summary

Description of key information

SKIN IRRITATION
corrosive, Cat 1 (R 34).
EYE IRRITATION
Corrosive Cat. 1; Irreversible effects to the eyes ( R 41).

Additional information

SKIN IRRITATION

In a primary dermal irritation study (BASF, 1982), young adult Vienna White rabbits) (1 male, 2 females) were dermally exposed to 0.5 ml of unchanged C5 acetate (purity not given) for 4 hours to a skin site sized 2.5 cm x 2.5 cm. Animals then were observed for 8 days. For further investigation, another 3 young adult Vienna White rabbits) (2 males, 1 female) were dermally exposed to 0.5 ml of unchanged C5 acetate (purity not given) for both 1 hour and 3 minutes to a skin site sized 2.5 cm x 2.5 cm. Irritation was scored by the method of Draize. The study was carried out in accordance with OECD TG 404.

Application for 4 hours produced strong erythema (mean score: 3.33) and edema (mean score: 1.67) as well as well-defined necrosis and skin bleeding. Erythema and edema were not fully reversible during the 8-day observation period. Necrosis was confirmed by pathological examination.

Application for 1 hour was irritating to the skin and produced well-defined erythema (mean score: 1.56) and edema (mean score: 0.33). Erythema persisted at the end of the observation period, while edema was fully reversible. Desquamation was noted for 1/3 animals.

Application for 3 minutes was not irritating to the skin; and produced only very slight erythema (mean score: 0.2) which was fully reversible.

In this study, C5 acetate is severely irritating to the skin based on the formation of necrosis after 4 -hour exposure.

 

The findings of this key study are confirmed by the results of two further, more ancient skin irritation studies.

 

In a primary dermal irritation study (BASF, 1969a); two rabbits were dermally exposed to 1 ml of unchanged C5 acetate (purity 94%) for 1, 5, and 15 minutes (short-term exposure, application to the back). Additionally, two further two rabbits were exposed to unchanged C5 acetate for 20 h (long-term exposure; application to the back and ear). Animals then were observed for 8 days. Irritation was scored by an internal BASF method; the scores of which are convertible to the Draize system.

No irritation was noted after application for 1 and 5 minutes. Erythema of grade 1 was reported after application for 15 minutes for 2/2 animals. The findings were reversible within 8 days.

Following 20-hour application to the back, edema of grade 4, superficial/soft anemic necrosis and skin bleeding were observed in 2/2 animals. After 8 days, well-defined, full-thickness necrosis with slight erythema at the margins and fissuring desquamation persisted in both animals.

Application to the ear produced well-defined erythema, very strong edema necrosis and skin bleeding; the necrosis was not reversible.

In this study, C5 acetate is severely irritating to the skin based on persisting necrosis observed after prolonged exposure. (Note: the exposure time of 20 hours exceeds the requirements of OECD TG 404.)

 

In another primary dermal irritation study (BASF, 1969b), two rabbits were dermally exposed to 1 ml of unchanged C5 acetate (purity >98%) for 1, 5, and 15 minutes (short-term exposure, application to the back). Additionally, two further two rabbits were exposed to unchanged C5 acetate for 20 h (long-term exposure; application to the back); these two animals and two further rabbits (i.e. totally 4) were also applied the unchanged test substance to the ear for 20 h. Animals then were observed for 8 days. Irritation was scored by an internal BASF method; the scores of which are convertible to the Draize system.

Only slight irritation was noted after application for 1, 5 and 15 minutes. Erythema of grade 1 was reported. The findings were reversible within 8 days.

Following 20-hour application to the back, erythema of grade 2, edema of grade 3 or 4 and skin bleeding was observed in 2/2 animals. After 8 days, well-defined, full-thickness necrosis persisted in both animals. Application to the ear produced necrosis and very strong edema in 4/4 animals; the findings were not reversible.

In this study, C5 acetate is severely irritating to the skin based on persisting necrosis observed after prolonged exposure at the back. (Note: the exposure time of 20 hours exceeds the requirements of OECD TG 404.)

 

EYE IRRITATION

In a primary eye irritation study (BASF, 1979), 0.1 ml of unchanged C5 acetate (purity not given) was instilled into the conjunctival sac of one eye of each of 6 albino rabbits (males and females; no data on sex ratio) for 4 hours. Treated eyes were washed after 4 h with water. Animals then were observed for 7 days. Irritation was scored by the method of Draize. The study was carried out in accordance with Federal Register Regulations.

C5 acetate produced mild to moderate corneal opacity in 6/6 rabbits, iritis in 1/6 rabbits, moderate conjunctivae redness, and marked chemosis. Iritis was completely reversible; corneal opacity, conjunctivae redness and chemosis persisted at the end of the 7-day observation. Mean irritation scores (24 – 72 h) were 1.78 (cornea), 0.56 (iris), 1.72 (conjunctivae redness) and 3.33 (chemosis). Mean total irritation score was 49 (range: 30 – 76; possible maximum: 110). Cornea findings did not show any trend to decrease in severity during the entire 8 -day observation period,

In this study, C5 acetate is moderately irritating to the eye based on the total irritation scores. Based on the persisting effects on the cornea, C5 acetate causes irreversible effects to the eye (R 41).

 

The findings of this key study are confirmed by the results of two further, more ancient eye irritation studies.

 

In a primary eye irritation study (BASF 1969a); 0.05 ml of unchanged C5 acetate (purity 94%) was instilled into the conjunctival sac of the right eye of 2 young adult Vienna White rabbits without rinsing. Animals then were observed for 8 days. Irritation was scored by an internal method, the scores of which are convertible to Draize scores.

Marked signs of irritation (corneal opacity, iritis, conjunctivae redness, chemosis and mucosal bleeding were observed). Mean scores (24-72h) were 2.5 (cornea), 1.5 (iris), 1.5 (conjunctivae redness) and 0.75 (chemosis). With exception of corneal opacity, findings were reversible within 8 days.

In this study, C5 acetate causes irreversible effects to the eye (R 41) based on persisting corneal opacity.

 

In another primary eye irritation study (BASF 1969b), 0.05 ml of unchanged C5 acetate (purity >98%) was instilled into the conjunctival sac of the right eye of 2 young adult Vienna White rabbits without rinsing. Animals then were observed for 8 days. Irritation was scored by an internal method, the scores of which are convertible to Draize scores.

Marked signs of irritation (corneal opacity, iritis, conjunctivae redness, chemosis and mucosal bleeding were observed). Mean scores (24-72h) were 1.5 (cornea), 2.0 (iris), 2.0 (conjunctivae redness) and 2.9 (chemosis). All findings were reversible within 8 days.

In this study, C5 acetate is moderately irritating to the eye (R 36) based on the degree/severity of iris effects and chemosis.

Justification for classification or non-classification

C5-acetate has to be classified as corrosive to the skin (R 34) according to the Directive 67/548/EC. According to GHS criteria, C5-acetate has to be classified as follows: corrosive Cat. 1C. Both classifications are based on the finding of well-defined necrosis observed after 4-hour exposure.

 

C5 acetate has to be classified as Irreversible effects to the eye (R41) according to the Directive 67/548/EC. According to GHS criteria, C5 acetate has to be classified as follows: corrosive, Cat. 1. Both classifications are based on the corneal opacity persisting at the end of the observation period without any indication of reversibility.