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Description of key information

In a supporting 5 days repeated dose oral toxicity study in rats with the registered substance, slightly reduced relative weights of liver and kidney were observed.

A supporting 14-day dose-range-finding study (LPT, 2013a) was done with read-across substance Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-18(even numbered) and C18 unsaturated)alkyl)amino]ethyl]esters, disodium salts in rats. 5 Male and 5 female rats were treated once daily with100, 300 and 1000 mg active ingredient/kg bw/day by oral administration. None of the animals died prematurely. Salivation was noted for 2 of 5 male animals treated with 1000 mg/kg bw/day on 1 or 3 test days starting on test day 9 and increased faeces was noted for 3 of 5 male and 2 of 5 female high dosed animals on 5 or 8 test days starting on test day 5. The food consumption of the male and female animals treated with 1000 mg/kgbw/day was slightly increased by 9% for the males and by 10% for the females in test week 2. None of the male and female rats treated orally with 100, 300 or 1000 mg/kg bw/day revealed any test item-related changes in body weight, body weight gain as well as relative and absolute organ weights or at macroscopic inspection at necropsy. After consideration of these data, the NOAEL was 300 mg/kg bw/day and following dose levels were selected for the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test of the read-across test item: 0, 100, 300 and 1000 mg active ingredient/kg bw/day.

In a key combinedreproduction and/or development toxicity study according to OECD guideline 422 (LPT, 2013b) with read-across substance Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-18(even numbered) and C18 unsaturated)alkyl)amino]ethyl]esters, disodium salts was dosed orally by gavage to rats at dose levels of 100, 300 and 1000 mg active ingredient/kg bw/day..No signs of clinical toxicity were noted for the male and female rats of the low and intermediate dose groups (100 and 300 mg/kg bw/day). A slightly increased salivation was noted in one male rat, no further signs of clinical toxicity were noted for the male and female rats of the high dose group (1000 mg/kg bw/day). No test item related influence was noted for the male and female rats of all treatment groups (100, 300 and 1000 mg/kg bw/day) during the observational and functional (grip strength and spontaneous motility) neurological screenings. A slight reduction in body weight was noted for the male and female rats of the high dose group (1000 mg/kg bw/day). For the male rats the reduction in body weight was noted from test day 8 (4.4%) until test day 36 (5.5%) and for the female rats from gestation day 0 (7.6%) until lactation day 4 (9.5%). The body weight at autopsy was reduced accordingly.The laboratory examinations revealed an increased ALAT activity for the male and female rats of the high dose group (1000 mg/kg bw/day) and a decrease in the albumin concentration for the male rats of the high dose group.No test item-related changes were noted during the macroscopic inspection at autopsy with the exception of changes in the stomach from 2 male animals from the high dose group (1000 mg/kg bw/day). Microscopic examination revealed the occurrence of squamous cell hyperplasia in the non-glandular mucosa and acute inflammation of the forestomach from the male and female rats of the high dose group (1000 mg test item/kg bw/day). Further microscopic findings occurred in form of pulmonary congestion in the male rats from the high dose group. NOAEL (no-observed-adverse-effect level) for repeated dose toxicity: 300 mg/kg bw/day.

Finally a supporting repeated dose dermal toxicity study on rabbits with the registered substance dosed at 0.357 mL/kg, 0.714 mL/kg and 1.428 mL/kg wiht a product (50 % aqueous solution) for 20 applications showed a mild to moderate irritation but no edema. No dose related effects occurred on body weight gain andfood consumption. The urine and blood data showed no significant deviations from thenorms, respectively between the initial and final readings. Neither the macroscopical northe microscopical histopathological examination of the tissues of 1 animal each of the group with the lowest and highest dose level revealed any serious damage. The treated skin ofthe animal treated showed slighthyperkeratosis and slight chronical inflammation in the stratum papilare.

Inhalation toxicity was waived as the exposure to workers is unlikely due to low vapour pressure

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Reliable
System:
gastrointestinal tract
Organ:
liver

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available
System:
gastrointestinal tract
Organ:
liver

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a supporting 5 days repeated dose oral toxicity study (Evonik, 1961) five rats were dosed with 2000 mg/kg bw SBU-185 by oral gavage on five consecutive days and two days after

the last application sacrificed. No animal died. There were no effects on clinical signs and body weight. Slightly reduced relative weights of liver (- 8 %) and kidney (- 16 %) were observed. No macroscopic alterations of heart and kidney were observed. 2/5 animals showed slightly increased redness of stomach mucosa. However, compared to the controls this was marginal

and inconclusive. Livers of treated animals were more yellow-brownish than livers of control animals.

In a key combined reproduction and/or development toxicity study according to OECD guideline 422 (LPT, 2013), read-across substance Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-18(even numbered) and C18 unsaturated)alkyl)amino]ethyl]esters, disodium salts was dosed orally by gavage to rats at dose levels of 100, 300 and 1000 mg active ingredient/kg bw/day. The study was preceded by a 14 -day dose range finding study; No test item-related premature death was noted in any treatment group (100, 300 and 1000 mg/kg bw/day). No signs of clinical toxicity were noted for the male and female rats of the low and intermediate dose groups (100 and 300 mg/kg bw/day). A slightly increased salivation was noted in one male rat, no further signs of clinical toxicity were noted for the male and female rats of the high dose group (1000 mg/kg bw/day). No test item related influence was noted for the male and female rats of all treatment groups (100, 300 and 1000 mg/kg bw/day) during the observational and functional (grip strength and spontaneous motility) neurological screenings. A slight reduction in body weight was noted for the male and female rats of the high dose group (1000 mg/kg bw/day). For the male rats the reduction in body weight was noted from test day 8 (4.4%) until test day 36 (5.5%) and for the female rats from gestation day 0 (7.6%) until lactation day 4 (9.5%). The body weight at autopsy was reduced accordingly. The laboratory examinations revealed an increased ALAT activity for the male and female rats of the high dose group (1000 mg/kg bw/day) and a decrease in the albumin concentration for the male rats of the high dose group. No test item-related changes were noted during the macroscopic inspection at autopsy with the exception of changes in the stomach from 2 male animals from the high dose group (1000 mg/kg bw/day). Microscopic examination revealed the occurrence of squamous cell hyperplasia in the non-glandular mucosa and acute inflammation of the forestomach from the male and female rats of the high dose group (1000 mg test item/kg bw/day). Further microscopic findings occurred in form of pulmonary congestion in the male rats from the high dose group. NOAEL (no-observed-adverse-effect level) for repeated dose toxicity: 300 mg/kg bw/day.

 

In a supporting repeated dose dermal toxicity study on rabbits (Evonik, 1965) dose levels of 0.357 mL/kg, 0.714 mL/kg and 1.428 mL/kg SBU 185 (50 % aqueous solution) were used. Only two animals per dose group were treated. An area of approximately 10% of the total body surface of the animals back was clipped free of hair. One animal's skin remained intact, the other animal's skin was abraded. The controls were prepared and treated in the same way, but no SBU 185 was used. Readings of the skin reactions were done daily during the period of the 20 applications. The skin reactions were evaluated comparable to Draize. Furthermore, the animals were observed for a two-week period, following final exposures. During the test and the observation period body weights, food consumption, and behavior were checked daily. Urine was checked at the beginning and at the end of the total test for the presence of protein, reducing substances, blood pigments or any abnormality in gross appearance. Also observations for changes in blood morphology were made. Microscopic examinations were made of the tissues of 1 animal each of the group with the lowest and highest dose level. The skin reactions observed show that SBU 185 (50 % aqueous solution) causes in all dose levels after 20 applications a mild to moderate irritation with erythema scores 0.1 to 3 but no edema. No dose related effects occurred on body weight gain and food consumption. The urine and blood data showed no significant deviations from the norms, respectively between the initial and final readings. Neither the macroscopical nor the microscopical histopathological examination of the tissues of 1 animal each of the group with the lowest and highest dose level revealed any serious damage. The treated skin of the animal treated with 1.428 mL SBU 185 (50 % aqueous solution)/kg bw showed slight hyperkeratosis and slight chronical inflammation in the stratum papilare.

Inhalation toxicity was waived as the exposure to workers is unlikely due to low vapour pressure.

Justification for classification or non-classification

Based on these results of registered and read-across substances, no classification and labelling is needed for repeated dose orall toxicity according to theCLP regulation (No. 1272/2008 of 16 December 2008).

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