Sodium O,O-di-sec-butyl dithiophosphate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

OECD 422: NOAEL (no-observed-adverse-effect level): 600 mg test item/kg b.w./day, p.o.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to Read Across Statement attached in Section 13

Reason / purpose for cross-reference:

read-across source

Species:

rat

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

No test item-related premature death was noted

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

A slight reduction in body weight was noted until the end of the study on test day 38 for the male rats of the high dose group (600 mg IBP1-Na/kg b.w./day). Body weight at autopsy was reduced accordingly

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

A slight reduction in body weight was noted until the end of the study on test day 38 for the male rats of the high dose group (600 mg IBP1-Na/kg b.w./day). Body weight at autopsy was reduced accordingly

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

The histopathological examination revealed test item related changes in the forestomach from male and female rats of the intermediate and the high dose group (200 and 600 mg IBP1-Na/kg b.w./day) in form of hyperplasia and hyperkeratosis of the squamous cell epithelium, infiltration with neutrophilic granulocytes, granulation tissue and ulcerations.
Additionally, test item-related changes were noted in the liver in the form of a centrilobullar hepatocellular hypertrophy at 600 mg/kg bw/day.

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

200 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: General health parameters

Key result

Dose descriptor:

NOAEL

Effect level:

600 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Reproductive parameters

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

In the high dose group the mean litter weight of the male and female pups was decreased by 5.6% on lactation day 1 and by 9.6% on lactation day 4 (without statistical significance). No noticeable differences were noted for the total litter weight

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

600 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: systemic effect

Reproductive effects observed:

not specified

 

The aim of the experiment was to obtain information on possible effects of the source substance, IBP1-Na on reproduction and/or development according to OECD guideline 422. Thesource substance was administered orally to rats at dose levels of 60, 200 or 600 mg IBP1-Na/kg b.w./day.

The application started two weeks before mating on test day one and ended on the day or one day before sacrifice. Day of sacrifice was on test day 38 for the male rats and between lactation day 4 and 5 for the female rats.

 

Effects on the parental generation

No test item-related premature death was noted.

At the intermediate and the high dose level (200 and 600 mg IBP1-Na/kg b.w./day) a slight to extreme salivation was noted in nearly all animals, with a higher incidence at the high dose level. Piloerection and an increased water consumption were noted for a few animals of the intermediate and the high dose group.

The neurological screening revealed a reduction for the hindlimb grip strength of the male and female animals of the high dose group (600 mg IBP1-Na/kg b.w./day).

A slight reduction in body weight was noted until the end of the study on test day 38 for the male rats of the high dose group (600 mg IBP1-Na/kg b.w./day). Body weight at autopsy was reduced accordingly.

Examination of the haematological and biochemical parameters revealed statistically significant changes in the male and female animals of the high dose group (600 mg IBP1-Na/kg b.w./day), which were considered as to be test item-related.

Macroscopic inspection at autopsy revealed test item related changes in the cardiac part of the stomach from 3 male animals of the intermediate dose group (200 mg IBP1-Na/kg b.w./day) and in the cardiac part of the stomach from 1 female animal of the high dose group (600 mg IBP1-Na/kg b.w./day).

Examination of the organ weights revealed a slightly statistically significant increase in the relative liver weight of the male rats of the high dose group (600 mg IBP1-Na/kg b.w./day).

The histopathological examination revealed test item related changes in the forestomach from male and female rats of the intermediate and the high dose group (200 and 600 mg IBP1-Na/kg b.w./day) in form of hyperplasia and hyperkeratosis of the squamous cell epithelium, infiltration with neutrophilic granulocytes, granulation tissue and ulcerations.

 

Additionally, a test item-related centrilobullar hepatocellular hypertrophy was noted In the liver from male and female animals of the high dose group (600 mg IBP1-Na/kg b.w./day).

 

Effects on reproduction parameters and organs

No test item-related influence was noted on the reproduction parameters and organs in any treatment group.

The qualitative sperm staging revealed no test item-related spermatogenic changes.

 

Effects on the development of the F1 offspring (pups)

A non-statistically significant reduction in mean litter weight of approximately 6% to 9% was noted on lactation day 1 and 4 for the male and female pups of the high dose group (600 mg IBP1-Na/kg b.w./day), which is regarded to be test item-related.

No test item related influence was noted on the survival rate of the pups.

 

The following no-observed-effect levels were established for systemic effects:

Effects on the F0-generation

NOAEL (no-observed-adverse-effect level):              200 mg IBP1-Na/kg b.w./day, p.o.

 

Effects on reproduction

NOAEL (no-observed-adverse-effect level):              600 mg IBP1-Na/kg b.w./day, p.o.

 

Remark: The test solution contains NaOH due to the production method.

 

Due to the similarity of the target substance, SBP1-Na, and the source substance, IBP1-Na, the result of this study is assessed to be adequate in order to fulfil the requirements of REACH. The read-across approach is further described in the document “Justification of read across from CAS No 53378-51-1, IBP1-Na (source) to CAS No 33619-92-0, SBP1-Na (target)” attached in “Point 13 Assessment reports”.

Conclusions:

NOAEL (no-observed-adverse-effect level): 200 mg test item/kg b.w./day, p.o. based on systemic effects and 600 mg/kg b.w./d based on reproductive effects.

Executive summary:

The test was performed according to OECD guideline 422 under GLP compliance. The test substance was administered orally to rats at dose levels of 60, 200 or 600 mg test item/kg b.w./day.

The following no-observed-effect levels were established for systemic effects: NOAEL (no-observed-adverse-effect level): 200 mg IBP1-Na/kg b.w./day, p.o.

The following no-observed-effect levels were established for reproductive effects: NOAEL (no-observed-adverse-effect level): 600 mg IBP1-Na/kg b.w./day, p.o.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

600 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

high quality

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

OECD 414: There were no treatment-related adverse effects on embryo-fetal development. Thus, the NOAEL for the maternal toxicity and embryo-fetal developmental toxicity is 800 mg/ kg body weight/ day.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

2016

Justification for type of information:

Please refer to Read Across Statement attached in Section 13

Reason / purpose for cross-reference:

read-across: supporting information

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

In the HD group animals there were signs of moving the bedding (8/8 females), slight salivation (2/8 females), moderate salivation (2/8 females), weight loss (5/8 females), abnormal breathing (3/8 females), slight piloerection (1/8 females), moderate piloerection (2/8 females), ataxia (1/8 females) and reduced spontaneous activity (1/8 females). None of these observations were considered as adverse effects of treatment with the test item.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

There was slightly lower mean body weight in HD group females (reduced by 3% to 6%) from GD 8 when compared to control values. The body weight gain was also lower between GD 5-8, 8-11, 14-17 and 17-20. The overall weight gain during the entire gestation period was 12% lower in HD group as compared to control. Considering the slight effect on body weight (<10%), the changes in body weight gain was considered to be of little toxicological relevance.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

There was a reduction in food consumption in HD group during the treatment period (lowered by 6% to 23% as compared to concurrent control values). These changes were not consistent and during the period of late gestation i.e from GD 17 onwards the food intake in HD group was lowered by only 5% as compared to control. The slight reduction in food intake was considered to be of little toxicological relevance.

Conclusions:

There were no overt signs of maternal toxicity and no signs of treatment-related embryo developmental toxicity under the conditions of the study.

Executive summary:

The test was performed according to OECD guideline 414. On the basis of this prenatal developmental toxicity study in Wistar pregnant female rats with test item at a dose level of 800 mg/kg body weight/ day administered on gestation days 5 to 19. There were no overt signs of maternal toxicity and no signs of treatment-related embryo developmental toxicity under the conditions of the study. Based on the data generated from this study and referring to an earlier OECD 422 study performed with the same test item at the doses of 60, 200 and 600 mg/kg body weight/day, the doses of 60, 300 and 800 mg/kg body weight/ day could be considered for the subsequent definitive OECD 414 study with test item.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

800 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

high quality

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the OECD Guideline studies with the test item no classification for developmental toxicity or toxicity to reproduction according to Regulation (EC) No 1272/2008 is warranted for the test item.