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: 417-790-1
CAS number: 78418-01-6
There is no reliable and relevant
information source in which the toxicokinetic properties (absorption,
distribution, metabolism, elimination) of MEXORYL SAB were investigated.
The expected toxicokinetic behaviour is derived from the physicochemical
properties and the results from the available toxicological data
following the guide given in the REACH guidance document R.7c:
MEXORYL SAB is a mono constituent
substance having a molecular weight of 264. It is a white powder with an
estimated water solubility of 30 mg/L. Volatility was determined to be
about 0.73 mmHg at 21°C (about 97 Pa) and has low lipophilic properties
(log Pow = 0.32). The surface tension is about 60-64 mN/m. Detailed
information can be found in section 4 of MEXORYL SAB IUCLID dossier.
In the oral acute toxicity study,
major signs of toxicity noted in all dose groups (2530, 3000, 3557 and
4217 mg/kg bw) were hunched posture, pilo-erection, lethargy, ptosis,
decreased or gasping respiration and red/brown staining around the snout
or mouth. Incidents of reduced bodyweight gain or bodyweight loss were
noted in all dose groups. Abnormalities noted at necropsy of animals
that died during the study were haemorrhagic or abnormally red lungs,
dark liver or patchy pallor of the liver, pale spleen, pale or dark
kidneys, haemorrhage or sloughing of the glandular gastric epithelium
and haemorrhage of the small and/or large intestines. The systemic toxic
effects observed (in particular lethargy, ptosis and loss of bodyweight)
show that MEXORYL SAB is absorbed by oral route at high doses.
In the dermal acute toxicity study, no
systemic effects were observed at 2000 mg/kg bw: no deaths, no clinical
signs and no abnormalities at necropsy. MEXORYL SAB has a low water
solubility (< 100 mg/L) therefore dermal uptake is considered to be low
or moderate. It is also a dry powder that would need to dissolve into
the surface moisture of the skin before uptake can begin. However,
MEXORYL SAB was found to be skin sensitizing therefore some uptake, even
limited, must have occurred. Thus, dermal absorption of MEXORYL SAB is
expected to be limited but not inexistent.
In a 4-week repeated dose toxicity
study, the dose level of the high dose group was dropped from 300 to 200
mg/kg bw/day on day 13 of the treatment period because of adverse
clinical signs (noisy and irregular/fast respiration), including death.
Bodyweight gain was reduced slightly (13-14 %) for males of the highest
dose group (associated with slight reduction in food consumption) and
for females given 100 mg/kg bw/day during the treatment period.
Macroscopic observations at necropsy revealed a dose-related increased
incidence of stomach abnormalities for animals given 100 and 300/200
mg/kg bw/day at the end of both the treatment and treatment-free period.
Microscopic pathology revealed hyperplasia of the non-glandular stomach
for animals given 300/200 mg/kg bw/day, accompanied by chronic
inflammation and ulceration. These effects seem related to irritant
local effects located in the stomach; systemic toxicity and maybe
absorption may be quite limited at this dose level. This hypothesis is
confirmed by the reproduction / developmental toxicity screening test:
no treatment-related effects were observed in rats exposed by oral
gavage up to the highest dose tested, i.e. 100 mg/kg bw/day.
Thus, indications of oral uptake of
MEXORYL SAB at high doses are given while dermal uptake would be more
limited even if skin irritation after repeated dose dermal exposure as
observed in the pre-developmental study, may enhance dermal absorption.
No study by
inhalation was performed. However, considering both the granulometry of
the powder and the physico-chemical properties of MEXORYL SAB, exposure
to MEXORYL SAB by inhalation is likely to occur. Indeed, exposure by
inhalation is possible based on a significant inhalable fraction of
MEXORYL SAB (from 13.23% to 26.7% particles < 100 µm) and a relative
high vapour pressure (97 Pa at 21°C) together with a melting point of
115°C. However, MEXORYL SAB could be
absorbed only at low rate based on both its low lipophilic properties
(log Pow = 0.32) and its relative low water solubility (29.7 mg/L).
Therefore the potential
bioavailability of MEXORYL SAB can be considered mainly by oral route.
The physico-chemical information (low
water solubility and low lipophilicity) indicates that distribution of
MEXORYL SAB could be quite limited, as it would not have particular
affinity for fatty tissues. This assumption is confirmed by the 4-week
repeated dose toxicity study where the toxic effects located in the
stomach may be more related to irritant local effects rather than
No data are available but, in in vitro
genotoxicity studies, differences in cytotoxicity were observed with and
without metabolic activation in Ames test and MEXORYL SAB was found
clastogenic in CHO cells only in presence of metabolic activation. This
indicates that MEXORYL SAB may be metabolised by hepatic microsomal
No data about the metabolism of
MEXORYL SAB are available. However, based on salicylic acid metabolism,
glucuronidation may be expected as a potential metabolic pathway for
As no toxic effects were observed in
kidneys in repeated toxicity studies, it is difficult to determine if
MEXORYL SAB is excreted in urine. However, based on the physico-chemical
information (low molecular weight, low water solubility), renal
excretion of MEXORYL SAB and/or its metabolites cannot be excluded.
Moreover, as MEXORYL SAB is considered to be potentially metabolized by
glucuronidation, it could be eliminated via bile excretion.
Based on the physico-chemical
information (log Pow = 0.32 and low water solubility), it is concluded
that the potential for bioaccumulation is low and it is not proposed for
classification as PBT substance.
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.
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