Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 204-464-7
CAS number: 121-32-4
Two studies have been selected as key study, a 90 day study and an OECD
In the 13-week study (Huntingdon et al. , 1992) performed on rats, the
NOAEL is 1000 mg/kg bw/day based on spleen weight which is higher than
control group (relative) related with histopathological changes. Based
on this pathability study, the NOAEL is 1000 mg/kg bw/day for effects on
In the OECD 421 study performed by gavage on 2017 (Charles River, 2017),
transient but adverse clinical signs were observed in male and female
rats at the dose level of 1000 mg/kg/day. A NOAEL of 500 mg/kg/day was
therefore identified for these effects.
In a subchronic
toxicity study (Hooks, 1992), ethylvanillin was administered to CD(SD)
BR rats (males and females, 20 per sex per dose), in diet at dose levels
of 0; 500; 1000; 2000 mg/kg/day for 13 weeks. Yellow discolouration of
some or all of the fur of rats treated with 500 mg/kg/day, 1000
mg/kg/day, or 2000 mg/kg/day, were not considered to be of toxicological
For males and females,
inferior bodyweight gain was recorded in the 2000 mg/kg/day group. For
males receiving 500 or 1000 mg/kg/day, the mean bodyweight gain was
inferior to that of controls during the first 4 weeks and the cumulative
mean food intake by all the male treated groups was stastistically lower
than that of controls. The food intake by females receiving 500 or 1000
mg/kg/day was considered to be similar to that of controls throughout
the study. The decrease of bodyweight gain is observed in the fourth
first weeks, related with a decrease in food consumption. This variation
is due to the unpathability of the substance, and was not considered to
related with toxicological property of the substance.
investigations showed slightly higher than control values for
glutamic-pyruvic transaminase, alkaline phosphatase, cholesterol and
total plasma protein at the high dosage level, only occasionally
involving the intermediate dosage level. These differences from control
may be related to treatment in view of the histopathological changes in
liver. The remaining differences from the control were considered
unlikely to be of toxicological importance.
observations done on the increase of liver weight (relative), it appears
to be not correlated with hepathological changes, because these effects
were observed in the control group too, that would be due to the strain
of rat used in this study. Therefore the increase of the liver weight is
not considered as adverse effect.
The NOAEL is 1000
mg/kg bw/day based on spleen weight which is higher than control group
(relative) related with histopathological changes.
Table: Summary of salient mean body weight changes of males (mean
values, in grams – percentage of difference with the control between
The test item, 3-ethoxy-4-hydroxybenzaldehyde (Ethylvanillin), was
administered by daily oral gavage to male and female Wistar Han rats at
dose levels of 250, 500 and 1000 mg/kg/day. A control group of 10
rats/sex was given the vehicle (Propylene glycol). Males were treated
for 31 days, i.e. 2 weeks prior to mating, during mating, and up to
termination. Females were treated during 2 weeks prior to mating, during
mating, during post-coitum, and up to the day before necropsy (i.e. on
day 13 of lactation for females delivered, on day 26 of gestation for
female with total litter resorption and on day 1 of lactation for
female with total litter death). The following observations and
examinations were performed: mortality / morbidity, clinical signs, body
weight, food consumption, estrous cycle determination, clinical
measurement of thyroid hormone T4, macroscopy at termination, organ
weights and histopathology on a selection of tissues.
All analyzed samples for formulations prepared at nominal concentrations
of 50, 100 and 200 mg/mL were in agreement with acceptance criteria and
no test item was present in the vehicle sample.
Furthermore, the test item prepared as a suspension in the vehicle was
homogenous. There was no test item-related mortality in any group.
Transient test item-related clinical signs in 5/10 females given 1000
mg/kg/day during the pre-mating period consisted of decreased activity
and/or abnormal breathing associated or not with partly closed eye(s),
piloerection, cold body and/or recumbency. A transient decreased
activity was observed also for 4/10 males at this dose level. The mean
body weight gain was lower than in controls in both males and females
during the pre-mating period in the 1000 mg/kg/day
group. Some females in all treated groups lost weight. The final mean
body weight of males and females in the high dose group was not,
however, overtly affected (-1 % for males on Day 29 and -5 % for females
on Day 15). There were no test item-related body weight changes
thereafter nor adverse changes in body weight gain at 250 and 500
mg/kg/day. Consistent with effects on body weight gains, there was a
slightly lower food consumption in the 1000 mg/kg/day female group than
in other groups.
In conclusion, 3-ethoxy-4-hydroxybenzaldehyde (Ethylvanillin) given by
oral gavage in male and female Wistar Han rats at dose levels of 250,
500 and 1000 mg/kg/day revealed transient parental toxicity (considered
as adverse) at 1000 mg/kg/day. Based on these results, a parental No
Observed Adverse Effect Level (NOAEL) of 500 mg/kg was derived.
studies were available by oral route (feed and gavage), but only 2 of
them were chosen as key study (Huntingdon, 1992 and Charles River,
2017). These 2 studies have the reliability 1 according to Klimish
a subchronic toxicity study (Huntingdon, 1992), Ethylvanillin was
administered to CD(SD) BR rats (males and females, 20 per sex per dose),
in diet at dose levels of 0 to 2000 mg/kg bw per day for 13 weeks.
The NOAEL is 1000 mg/kg bw/day based on spleen weight which is higher
than control group (relative) related with histopathological changes. In
a subacute toxicity study (Dose-range finding) (Huntingdon, 1992)
(selected as WOE), ethylvanillin was administered to CD(SD) rats (males
and females, 10 per sex per dose), in diet at dose levels of 0 to 2000
mg/kg bw/day for 2 weeks. The
NOAEL is 1000 mg/kg bw/day based on bodyweight gain.
OECD 421 study performed on rats in 2017 (Charles River, 2017) was also
selected as a key study. Such study is not really design to assess
repeated toxicity. However in this study transient but adverse clinical
signs were observed in male and female rats at the dose level of 1000
mg/kg/day. Therefore based on this study a NOAEL of 500 mg/kg/day was
identified in rats. Since this NOAEL is lower than the NOAEL identified
in the 90 day study, the OECD 421 study was retained, in a conservative
approach, for the derivation of the DNELs.
In the different studies available, ethylvanillin did not show
adverse systemic effects up to 500 mg/kg/day, and should not be
classified for repeated toxicity or STOT repeated exposure, according to
the CLP 1272/2008 criteria.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
På den här webbplatsen används kakor. Syftet är att optimera din upplevelse av den.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again