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Description of key information

LD50 oral (rat): 3978 mg/kg bw. Vanilline is not harmful by ingestion.
LD50 dermal (rat): > 2000 mg/kg bw (no mortality observed at this dose). Vanilline is not harmful by dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
3 978 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50

Additional information

Acute oral toxicity

Seven studies were available which 3 of them were of validity 2.

All data gave LD50 results above 2000 mg/kg, except results in Jenner (1964) publication (1580 mg/kg in rat and 1400 mg/kg in guinea pig) which was not taken into consideration, because it was validity 3 according to Klimish scale.

The three studies with validity 2 (Hazleton 1992, Monsanto 1955 and 1976,) were selected as key studies. The results were similar, the study ofHazleton(1992), was the most detailed.

In this study groups of fasted, 5-7 weeks old Sprague-Dawley rats (5/sex) were given a single oral dose of crystallised Vanilline (purity unknown) in CMC at doses of 0, 2000, 2510, 3160 and 3980 mg/kg bw and observed for 15 days. Lethargy, prostration or subdued behaviour were observed in all groups, and sialorrhea was observed in some animals. Death occurred in animals tested of main experiment: for limit test 2/10 at 2000 mg/kg bw for principal study: 0/10 at 0 mg/kg bw 1/10 at 2000 mg/kg bw 2/10 at 2510 mg/kg bw 3/10 at 3160 mg/kg bw 5/10 at 3980 mg/kg bw. In the preliminary study, 3 groups of 2 males and 2 females per group were treated under the same conditions as those employed in the main study, at the dose levels of 500, 1000 and 2000 mg/kg. Animals were observed for 15 days. Neither clinical signs nor death were seen at all dose level tested.

Oral LD50 Combined Males/Females = 3978 mg/kg bw (95% C.I. 2484 - 6368 mg/kg bw) according to Bliss' method

The key studies provided a LD50 range from 3300 to 3978 mg/kg.

According to classification criteria of EC regulation 1272/2008 Vanillin should not be classified for acute oral toxicity.

Inhalation route:

Only one study on rat (Makaruk, 1980) was available. In this study, only one dose was tested which is the saturated vapour concentration. It gave a result of LC50 above 41.7 mg/m3after 4 hours exposure for rats and 2 hours for mouse with no other details. It was in validity 3 according to Klimish scale, and no purpose flag was selected.

Dermal route:

In an acute dermal toxicity study (Hazleton, 1991) of validity 2, groups of 5 -7 weeks old Sprague-Dawley rats (male / female) were dermaly exposed to Vanillin for 24 hours to approximately 10% area of the body at doses of 2000  mg/kg bw.  Animals then were observed for 14 days.

 In the preliminary study, 2 males and 2 females per group were treated under the same conditions as those employed in the main study, at the dose levels of 1000 and 2000 mg/kg. No deaths were seen at all dose level tested of 2000 mg/kg.

 

Dermal LD50 Combined>2000mg/kg bw. No clinical sign, except yellowish coloration of the skin and no mortality occurred at this dose.

 

According to classification criteria of EC regulation 1272/2008 Vanillin should not be classified for acute dermal toxicity based on the LD50 in male and female rats.

Justification for classification or non-classification

Regarding data available, vanilline was not classified for acute toxicity by oral and dermal routes.