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EC number: 239-622-4
CAS number: 15571-58-1
The evaluation of the repeated dose toxicity was based on three studies:- Two subchronic oral toxicity tests (rat) with mixtures containing a high concentration of DOT(2 -EHMA) (70 and 97% purity)- no guideline studies;- One subchronic toxicity test (dog) with Dioctylin bis (IOMA) and dioctyltin bis (2-EHMA) which are isomers of the same compound and are structural analogues of each other. Based on the recently conducted developmental toxicity studies in two species it is considered that DOTI is likely to be more toxicoligically active and therefore use of data on this substance would be considered to be a worst case assessment of the registered substance.No data on dermal or inhalatory repeated dose toxicity are available.
A repeated dose oral toxicity study was
carried out with rats and a mixture of Dioctyltin bis(2-EHMA) [CAS No.
15571-58-1]:Octyltin tris(2-EHMA) [CAS No. 27107-89-7]: Trioctyltin
(2-EHMA) [CAS No. 61912-55-8] (97.0:0.3:2.17% mixture). The study
predates GLP, but is well documented and quality assurance is
comparable. No information on the homogeneity or stability of the test
substance in the diet was provided, due to which the study was
considered less reliable. The NOAEL was determined to be 10 ppm
(equivalent to 0.5 mg/kg bw/day) and the LOAEL was determined to be 25
ppm (equivalent to 1.3 mg/kg bw/day) based on reduced thymus weight.
evaluation of the repeated dose toxicity of the substance was based on
the findings of three studies, as follows.
key study (anonymous, 1970) repeated dose oral toxicity of a mixture of
Dioctyltin bis(2-EHMA) [CAS No. 15571-58-1]:Octyltin tris(2-EHMA) [CAS
No. 27107-89-7]: Trioctyltin (2-EHMA) [CAS No. 61912-55-8]
(97.0:0.3:2.17% mixture) was evaluated in rats dosed continuously via
the diet at concentrations of 10, 25, 50, 250, 100, 500 and 1000 ppm.
Fifteen rats per sex received each dose for a period of 90 days. Body
weights, food and water consumption were recorded and blood samples were
collected in weeks 6 and 12 for haematological and clinical chemistry
evaluation. At the end of the experimental period, animals were
sacrificed and subject to pathological and histopathological examination.
the conditions of the study the no-observable-adverse-effect-level
(NOAEL) was determined to be 10 ppm in the diet (equivalent to 0.5
mg/kg/bw/day) of rats exposed for 90 days, on the basis of reduced
thymus weight at 25 ppm.
supporting study (anonymous, 1974) repeated dose oral toxicity of
Dioctyltin bis(2-EHMA) [CAS No. 15571-58-1]:Octyltin tris(2-EHMA) [CAS
No. 27107-89-7] (70:30% mixture) was evaluated in rats dosed
continuously via the diet at concentrations of 25, 50 and 100 ppm.
Twenty rats per sex received each test diet for a period of 90 days.
Blood and urine samples for haematology and biochemistry were collected
during weeks 5, 9, and 13. Clinical symptoms of toxicity were recorded
daily, and body weights and food consumption were recorded weekly. An
ophthalmic examination was conducted pre-exposure and in rats from the
25 and 100 ppm dose groups, during weeks 5, 9, and
13.The following organs were weighed at necropsy: adrenals, kidneys, brain, liver, heart, gonads, and thymus.
The following organs and tissues were collected for histopathological examination: adrenals, brain, gonads, kidneys, lymph nodes, muscle,
pituitary, spleen, thymus, aorta, colon, gross lesions, liver, pancreas, prostate, uterus, spinal cord, thyroids, bone marrow,
eye, heart, lungs, mammary gland, sciatic nerve, small intestine, stomach, and urinary bladder.
deaths occurred and no clinical symptoms of toxicity were recorded. Body
weight gains, food consumption, clinical chemistry, and urine analysis
for treated rats were comparable to the control group. Ophthalmic
examination did not reveal any abnormalities in treated rats. There was
a significant dose-related reduction in absolute and relative thymus
gland weights in the 50 ppm (3.3 mg/kg) and 100 ppm (6.6 mg/kg) dose
The no effect level for
was determined to be 25 ppm (calculated as 1.25 mg/kg/day, based on a food factor of 0.05)
based on reduced absolute and relative thymus gland weights.
In the supporting study reported by Johnson
(1970) repeated dose toxicity the
structural analogue Di(n-octyl) tin S, S'-bis (isooctylmercaptoacetate),
was evaluated in dogs dosed continuously via the diet at concentrations
of 0, 20, 50, and 150 ppm. Three dogs per sex received each test diet
for a period of 14 weeks. The animals were observed for mortality, body
weight, general physical condition and weekly physical examinations,
blood pressure, electrocardiograms and eye examinations. Haematology and
clinical chemistry determinations were performed at weeks 0, 4, and 13.
The dogs were sacrificed after 14 weeks and subjected to gross
pathological and histopathological assessment.
animals survived the duration of the experiment and maintained good
physical condition throughout. There were no treatment related effects
on body weights, food consumption, urinalysis, haematology, clinical
chemistry and ophthalmic examinations were negative except for one
animal. No gross pathological or histopathological changes were noted.
under the conditions of the study the NOAEL was determined to be 150
ppm, the highest dose level tested.
from the study reported by Appel (2004) are included in the dataset
since the test material was previously regarded as being an adequate
substance for read-across to the registered substance since DOT(2-EHMA)
had previously been demonstrated to be readily hydrolysed to
Dichlorodioctyltilstanane (CAS no.3542-36-7) under physiological
conditions (see section 7.1.1). Thus DOTC(Dichlorodioctylstannane) was
considered to be an appropriate anchor compound and surrogate for the
mammalian toxicology endpoints of repeated dose, in vivo genetic
toxicity, reproduction and developmental effects, when it is dosed via
the oral route of administration.
read-across to the substance DOTC is no longer considered as wholly
appropriate based on the results of the recent Hydrolysis studies, as
reported by Naßhan H 2014 and Naßhan, H, 2015 (see section 7.1.1) which
indicate the substance DOTECl is the only metabolite of DOTE which is
formed in a simulated mammalian gastric environment; no
dioctyltindichloride was formed under the conditions of the study.
Findings from the study reported by Appel (2004) have therefore been
disregarded and are not included in the overall assessment of repeated
dose toxicity of the registered substance.
Based on the available data on the substance
it self ( pure and mixture) and on the gastric hydrolysis product (pure
DOTC 94%), DOT(2-EHMA) is classified as T: R48/25 according to
Directive 67/548/EEC and according to CLP : STOT RE category 1 for
specific target organ toxicity, specifically for effects on the thymus
Justification: A LOAEL is 0.7 mg/kg bw/d.
This value is smaller than 10, therefore a classification 'STOT RE 1' is
required according to the regulation EC no.1272/2008 (CLP).
This value is smaller than 5 mg/kg bw/d,
therefore according to the Directive 67/548/EEC, the substance is
classified "R48 /25" (with a LOAEL between 5 and 50 mg/kg bw/d
: R48 /22).
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.
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