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EC number: 947-115-0
CAS number: -
Under the conditions of a combined
Repeated Dose Toxicity Study with the Reproduction / Developmental
Toxicity Screening Test (OECD TG 422 ), the oral administration of
the test item via the drinking water to Wistar rats revealed adverse
findings at 284 mg/kg bw/d (whole product) regarding clinical signs,
body weight, food and water consumption. Thus, the no observed adverse
effect level (NOAEL) for general systemic toxicity was 245 mg/kg bw/d
(whole product) [BASF, 2019]. With regard to the content of
Disodium (sulphonatothio)acetate and sodium chloride (38% of whole
product), this corresonds to a NOAEL for general systemic toxicity of 93
Table 6: Mean test substance intake (mg/kg bw/d) of whole product
Disodium (sulphonatothio)acetate and sodium chloride (38% of whole
Test group 1
Test group 2
Test group 3
(study days 0-13)
Mean values of entire administration period
Disodium (sulphonatothio) acetate and sodium chloride (38% of whole product)
Test group (ppm)
Final body weight
≤ 0.05; **p ≤ 0.01
Vagina and Cervix
No. of animals
Oral repeated dose toxicity
The oral repeated dose toxicity of Reaction
mass of Disodium (sulphonatothio)acetate and sodium chloride was
investigated by means of a Combined Repeated Dose Toxicity Study with
the Reproduction/Developmental Toxicity Screening Test according to OECD
TG 422 and GLP.
Reaction mass of Disodium
(sulphonatothio)acetate and sodium chloride was given daily as a
solution to groups of 10 male and 10 female Wistar rats (F0 animals) via
the drinking water at concentrations of 0, 750, 2500 and 7500 ppm (whole
product consisting of 38% of Disodium (sulphonatothio)acetate and sodium
chloride as well as about 62% of water). Control animals were dosed
daily with the vehicle only (drinking water). Due to reduced food and
water consumption and reduced body weight/body weight change values in
animals of test group 3 (7500 ppm), the concentration for this test
group was reduced to 6000 ppm from study day 13 onwards (end of
The duration of treatment covered a 2-week
premating period and mating in both sexes (mating pairs were from the
same test group) as well as entire gestation and lactation period in
females up to the day of schedule sacrifice of the animals. Due to
naturally occurring increased water consumption of female animals during
lactation and, consequently, a much higher test-substance intake, the
concentrations for all test groups were reduced on purpose by 50% from
delivery until sacrifice.
Observations: The parents' and the pups'
state of health was checked each day, and parental animals were examined
for their mating and reproductive performances. F0 animals were mated
for a maximum of two weeks after the beginning of treatment to produce a
litter (F1 generation pups). As soon as sperm was detected in the
vaginal smear, mating was discontinued. F0 animals were examined for
their reproductive performance including determinations of the number of
implantations and the calculation of the postimplantation loss in all F0
females. A detailed clinical observation (DCO) was performed in all
animals before initial test substance administration and, as a rule,
thereafter at weekly intervals. Food consumption of the F0 parents was
determined regularly once weekly before and after the mating period, as
well as in dams during gestation days 0-7, 7-14 and 14-20 and lactation
days 1-4, 4-7, 7-10 and 10-13. In general, the body weights of F0
animals were determined once a week. However, during gestation and
lactation, F0 females were weighed on gestation days (GD) 0, 4, 7, 10,
14 and 20, and on postnatal days (PND) 0, 4, 7, 10 and 13. The pups were
sexed and examined for macroscopically evident changes on PND 0. They
were weighed on PNDs 1, 4, 7 and on PND 13 and their viability was
recorded. On day 1 after birth the anogenital distance (AGD) was
determined on all live male, female and uncertain pups. On PND 4, the
individual litters were standardized in such a way that, whenever
possible, each litter contains 4 male and 4 female pups (as a rule, the
first 4 surviving pups/sex in each litter were taken for further
rearing). On PND 13, all male F1 pups were examined for retention of
nipples/areolae. The number of nipples/areolae anlagen were counted. At
necropsy on PNDs 4 and 13, all pups were sacrificed with CO2 under
isoflurane anesthesia and examined macroscopically for external and
visceral findings. Blood samples were taken from all surplus pups per
litter at PND 4 as well as one male and one female pup per litter at PND
13 by decapitation under isoflurane anesthesia. Additionally, blood
samples from all dams at PND 14 and all males at termination were taken
by puncturing the retrobulbar venous plexus under isoflurane anesthesia.
Thyroid glands/parathyroid glands were fixed in neutral buffered 4%
formaldehyde solution and transferred to the Laboratory Pathology for
possible further processing. Towards the end of the administration
period, a functional observational battery was performed, and motor
activity was measured in 5 parental animals per sex and test group.
Clinico-chemical and hematological examinations were performed in 5
parental animals per sex and group towards the end of the administration
period. All F0 parental animals were sacrificed by decapitation under
isoflurane anesthesia and were assessed by gross pathology. Weights of
selected organs were recorded, and a histopathological examination was
The various analyses confirmed:
• the stability of the test-substance
preparations for a period of 7 days at room temperature,
• the homogeneous distribution of the test
substance in the vehicle,
• the correctness of the prepared
concentrations in most preparations.
The following test substance-related,
relevant findings were noted:
Test group 3: 7500 ppm (between study
days 0 to 13)
F0 PARENTAL ANIMALS
Clinical Examination, Reproductive
Performance, Clinical Pathology and Pathology
• Piloerection was observed in a single male
animal between study days 9 to 12.
• Decreased water consumption in male and
female animals showing a maximum deviation of -45% on study day 7 in
males and -48% on study day 3 in females.
• Decreased food consumption in male and
female animals showing a maximum deviation of -22% in males and -21% in
females on study day 7.
• Impaired body weight development in male
and female animals including body weight loss between study days 0-7 in
male animals and between 0-3 in female animals.
Test group 3: 6000 ppm (from study day
• No treatment-related, adverse effects were
Clinical Examinations/ Gross Findings
Test group 2: 2500 ppm
Test group 1: 750 ppm
Conclusion: Under the conditions of
this Combined Repeated Dose Toxicity Study with the
Reproduction/Developmental Toxicity Screening Test, the oral
administration via drinking water of Reaction mass of Disodium
(sulphonatothio)acetate and sodium chloride to Wistar rats revealed
signs of toxicity in male and female animals at a concentration of 7500
ppm (whole product). No adverse signs of toxicity were observed at a
concentration of 6000 ppm (whole product). Thus, the no observed adverse
effect level (NOAEL) for general systemic toxicity was 6000 ppm for male
(245 mg/kg bw/d) and female Wistar rats (453 mg/kg bw/d).
With regard to the content of Disodium
(sulphonatothio)acetate and sodium chloride (38% of whole product), this
corresonds to a NOAEL for general systemic toxicity of 93 mg/kg bw/d and
172 mg/kg bw/d for males and females, respectively.
The NOAEL for reproductive performance and
fertility was set to 7500/6000 ppm for male and female Wistar rats. The
NOAEL for developmental toxicity was 7500/6000 ppm.
This study was chosen as key study, since
compared to the supporting study, higher dosages were tested at which no
adverse effects were observed. Moreover this GLP-conform study was
conducted according to the newest guideline version.
The test substance (ca. 39.5 % test
substance preparation) was administered to male and female Wistar rats
for 4 weeks in drinking water at nominal concentrations of 0; 300; 2000
and 12000 ppm (0, 11, 62, 287 mg/kg). Based upon analytically found
concentrations and recorded water consumption and body weights, these
concentrations corresponded to a test substance intake (active
ingredient) of 0; 11, 62, and 287 mg/kg body weight/day, respectively.
Five animals per sex of all groups were
treated for 4 weeks and sacrificed thereafter; the remaining 5 animals
per sex of control and high dose group were maintained for another 2
weeks without administration of the test substance (recovery period).
At the high concentration, water consumption
was impaired in both sexes during the administration period. Also food
consumption, body weights and food efficiency (day 7 only) were
statistically significantly lower than controls, most probably as a
consequence of the impaired water consumption. For all parameters, a
recovery could be observed, although recovery from the impairment of
body weight in high dose males was not complete until the end of two
2-week treatment free period.
The slight increase in serum alanine
aminotransferase activities seen in the high dose males is indicative of
mild hepatocellular damage at dose levels of 287 mg/kg bw/day.
The increases in urea concentrations in the
sera of the high dose males and females are possibly due to mild
impairment of kidney function. Dysfunction of the kidneys coupled with
increased renal loss of magnesium may be the cause of slight
hypomagnesemia seen in the high dose females. On the other hand, the
excretion of decreased amounts of concentrated urine demonstrates the
ability of the kidneys to concentrate the urine. High urinary specific
gravity indicate adequate renal function to maintain normal homeostasis.
Since there is no evidence of a nephrotoxic effect, the mechanism of the
aforementioned changes in serum and urine parameters are due to reduced
water consumption rather than damage to or functional impairment of the
kidneys. Moreover, the decreases in serum creatinine and albumin
concentrations seen in the high dose females are probably associated
with the reduced food consumption and body weight of the animals given
287 mg/kg bw/day of the test compound.
Histopathology revealed no findings which
could be attributed to the test substance administration.
Thus the NOAEL in this study was at ca. 62
and Packaging Regulation (EC) No. 1272/2008
The available experimental
test data are reliable and suitable for classification purposes under
Regulation 1272/2008. As a result, the substance is not considered to be
classified for repeated dose toxicity under Regulation (EC) No.
1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.
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