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EC number: 447-920-2
CAS number: 897393-42-9
Repeated dose toxicity - oral: van Otterdijk (2003) performed a subacute
28 -day oral toxicity test with the substance by daily gavage in the rat
(50, 150 and 1000 mg/kg bw/d dose levels) according to OECD Guideline
407 and EU Method B.7. On the basis of the very slight and/or transient
body weight effects at 150 mg/kg/day, and the sporadic appearance of
clinical signs throughout the study that were in the absence of any
histopathological findings, the NOAEL is considered to be 150 mg/kg/day
(instead of 50 mg/kg bw/d as concluded in the study report).
In addition, Chase (2011) performed a subchronic 90 -day oral toxicity
test with the test substance by daily gavage in Crj:CD(SD) rats
according to OECD Guideline 408. The substance was administered for 90
consecutive days at dose levels of 15, 50 and 150 mg/kg/day. The NOAEL
was considered to be 150 mg/kg/day.
Repeated dose toxicity - inhalation: Neither the properties of the
substance nor exposure considerations trigger the need for a repeated
dose toxicity study via inhalation or the dermal route.
Repeated dose toxicity - dermal: Neither the properties of the substance
nor exposure considerations trigger the need for a repeated dose
toxicity study via inhalation or the dermal route.
Analysis of dose preparations:
Analysis of the accuracy of dose preparations revealed values within the
range of 68 -105% of nominal. This variation was considered to be
related to the analytical method/test substance properties, and was
smaller than the variation seen with the procedural recoveries. Also
taking into account the high water solubility of the test substance,
formulations in water (Milli-U) were considered to be stable for at
least 4 hours and to be prepared homogeneously and accurately at the
Repeated dose toxicity: oral
van Otterdijk (2003) performed a subacute 28 -day oral toxicity study
with the substance by daily gavage in the rat. Based on the results of a
5-day range finding study, the dose levels for the 28 -day toxicity
study were selected to be 0, 50, 150 and 1000 mg/kg/day.
The study was based on the following guidelines:
- EC Directive 96/54/EEC, B.7 Repeated Dose (28 days) Toxicity (oral),
- OECD 407, Repeated dose 28 -day Oral Toxicity Study in Rodents, 1995
- OPPTS 870.3050, Repeated dose 28 -day oral toxicity study in rodents
The test substance was administered daily for 28 days by oral gavage to
SPF-bred Wistar rats. One control group and three treated groups were
tested, each consisting of 5 males and 5 females. The following
parameters were evaluated: clinical signs daily; functional observation
tests; body weight and food consumption weekly; clinical pathology and
macroscopy at termination; organ weights and histopathology on a
selection of tissues.
Treatment of Wistar rats with the substance for 28 consecutive days by
oral gavage at dose levels up to 1000 mg/kg/day resulted in the
premature sacrifice or death of all high dose animals. Stomach effects
(forestomach hyperplasia and ulceration) were considered to be
contributory to death or the retarded health condition of these animals,
and point to corrosive/irritating properties of the test substance.
Corroborative signs of ill-health were noted during treatment together
with reduced food intake and food conversion efficiency, and a marked
reduction of weight gain.
Transient lower body weight gain was also obtained for animals dosed at
150 mg/kg/day, but without supportive changes in food intake. In this
dose group, piloerection was noted among all females with hunched
posture, leanness and general swelling of the skin observed less
frequently. However, no stomach abnormalities were noted at 150
mg/kd/day. Decreased epididymis weights in high dose males was
considered to have occurred secondary to the markedly reduced body
weight gain and the overall condition of these animals. There were no
changes in performance of neurological functional observations that were
considered to be an effect of treatment. At 150 mg/kg/day, clinical
signs (in the absence of histopathological changes), the LOAEL is
considered to be 150 mg/kg/day and the NOAEL to be 50 mg/kg/day.
However, on the basis of the very slight and/or transient body weight
effects at 150 mg/kg/day, and the sporadic appearance of clinical signs
throughout the study that were in the absence of any histopathological
findings, it is considered that 150 mg/kg/day is the NOAEL for this
Chase (2011) performed a subchronic 90-day oral toxicity study with the
substance by daily gavage in the rat. The rats were administered for 90
consecutive days by oral gavage at dose levels of 15, 50 and 150
mg/kg/day. This study also included enhanced sperm mobility and
histopathology evaluations to clarify the results of the sperm
evaluations from the two-generation reproductive toxicity study. There
were no deaths to the study animals during the study. The appearance and
behaviour of the animals were unaffected by treatment. Bodyweight gain,
food consumption and organ weights were unaffected by treatment. There
were no macroscopic or microscopic findings that were associated with
treatment. Sensory reactivity, grip strength and motor activity were
unaffected by treatment. There were no changes in the performance of
neurological functional observations that were considered to be an
effect of treatment. There were no effects of treatment on sperm number
or morphology. The NOAEL was considered to be 150 mg/kg/day. This study
supports the results of the 28 day repeated dose test with a NOAEL of
The results of this study indicate that there are no effects on sperm
number, motility or morphology at 150 mg/kg/day and support the
conclusion that the substance is not a reproductive toxicant.
Repeated dose toxicity: inhalation and dermal
Neither the properties of the substance nor exposure considerations
trigger the need for a repeated dose toxicity study via inhalation or
the dermal route.
The NOAEL for systemic toxicity was 150 mg/kg in the 90-day oral
toxicity study. Because the Guidance Value Range to assist in potential
STOT RE classification (specific target organ toxicity repeated
exposure) is 10 - 100 mg/kg/day for the oral route of exposure, no
classification is justified for the substance according to the CLP
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