3-[4-[[5-(1,1-dimethylpropyl)-2-hydroxy-3-nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulphonamide, reaction products with aqueous organic chromium(III) complex sodium salt, then laked with acidified C10-14-tert-alkyl(linear and branched) amines

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

In a Reproductive/Developmental Screening Test the oral administration of the test item to Wistar rats resulted in the following Effect levels:
NOAEL for general systemic toxicity was 12000 ppm (812 mg/kg bw) for male and 3600 ppm (261 mg/kg bw) for female rats.
NOAEL for fertility and reproductive performance was 12000 ppm (812 mg/kg bw).

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

812 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The test item was tested for oral reproductive/developmental toxicity in a screening test with rats according to OECD guideline 421 (BASF 2016, 81R0371/13R081). The test substance was administered orally via diet to groups of 10 male and 10 female Wistar rats (F0 animals) at concentrations of 0 ppm, 1200 ppm, 3600 ppm and 12000 ppm. The overall average dose of the test item administered to the male and female Wistar rats during the entire study was approx. 85 mg/kg body weight/day (mg/kg bw/d) in the 1200 ppm group, approx. 261 mg/kg bw/d in the 3600 ppm group and approx. 812 mg/kg bw/d in the 12000 ppm group. The duration of treatment covered a 2-week premating and a mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation and 2 weeks thereafter in females. Analyses confirmed the overall accuracy of the prepared concentrations and the homogeneity of the test substance in the vehicle. The stability of these preparations was also demonstrated over a period of 7 days under refrigerated conditions.
Signs of general systemic toxicity were observed in female parental animals of the 12000 ppm test group taking reduced food consumption and impaired body weight development into account. Females showed decreased food consumption during premating days 0-7 and 0-13 (about 14% and 9% below control, respectively), during the entire gestation period (up to 15% below control) and during the entire lactation period (about 31% below control). Decreased body weights in the females on GD 20 (about 7% below control) and during the entire lactation period (up to 14% below control) was observed. Further, decreased body weight change in the females during PND 1-4 (about 67% below control) occurred. No signs of general systemic toxicity were observed in male parental animals at 12000 ppm as well as in male and female animals of the 1200 and 3600 ppm test groups. Fertility, reproductive performance and delivery were not impaired by test-substance up to a concentration of 12000 ppm, as was demonstrated by unchanged fertility, gestation and live birth indices of pups in all test groups. Regarding pathology, the terminal body weight of the parental females at 12000 ppm was significantly decreased (94%), which was regarded as treatment-related. All other findings occurred either individually or were biologically equally distributed about control and treatment groups. They were considered to be incidental and spontaneous in origin and without any relation to treatment.
Under the conditions of the present Reproduction/Developmental Toxicity Screening Test the oral administration of the test item to male and female Wistar rats resulted in signs of systemic toxicity at a concentration of 12000 ppm in female animals. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 12000 ppm for male and 3600 ppm in female Wistar rats. The no observed adverse effect level (NOAEL) for fertility and reproductive performance was 12000 ppm.

Effects on developmental toxicity

Description of key information

In a Reproductive/Developmental Screening Test the oral administration of the test item to Wistar rats resulted in the following Effect levels: NOAEL for general systemic toxicity was 12000 ppm (812 mg/kg bw) for male and 3600 ppm (261 mg/kg bw) for female rats. NOAEL for developmental toxicity was 3600 ppm (261 mg/kg bw).

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

261 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

The test item was tested for oral reproductive/developmental toxicity in a screening test with rats according to OECD guideline 421 (BASF 2016, 81R0371/13R081). The test substance was administered orally via diet to groups of 10 male and 10 female Wistar rats (F0 animals) at concentrations of 0 ppm, 1200 ppm, 3600 ppm and 12000 ppm. The overall average dose of the test item administered to the male and female Wistar rats during the entire study was approx. 85 mg/kg body weight/day (mg/kg bw/d) in the 1200 ppm group, approx. 261 mg/kg bw/d in the 3600 ppm group and approx. 812 mg/kg bw/d in the 12000 ppm group. The duration of treatment covered a 2-week premating and a mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation and 2 weeks thereafter in females. Analyses confirmed the overall accuracy of the prepared concentrations and the homogeneity of the test substance in the vehicle. The stability of these preparations was also demonstrated over a period of 7 days under refrigerated conditions.
Signs of general systemic toxicity were observed in female parental animals of the 12000 ppm test group taking reduced food consumption and impaired body weight development into account. Females showed decreased food consumption during premating days 0-7 and 0-13 (about 14% and 9% below control, respectively), during the entire gestation period (up to 15% below control) and during the entire lactation period (about 31% below control). Decreased body weights in the females on GD 20 (about 7% below control) and during the entire lactation period (up to 14% below control) was observed. Further, decreased body weight change in the females during PND 1-4 (about 67% below control) occurred. No signs of general systemic toxicity were observed in male parental animals at 12000 ppm as well as in male and female animals of the1200 and 3600 ppm test groups. Fertility, reproductive performance and delivery were not impaired by test-substance up to a concentration of 12000 ppm, as was demonstrated by unchanged fertility, gestation and live birth indices of pups in all test groups. The viability index as indicator for pup mortality in early lactation was also not significantly altered. Pup weights (average 24.6% below control) and weight gain (average 49% below control) were significantly lower in the high-dose group (12000 ppm). The bigger part of this developmental delay can certainly be attributed to the distinct maternal toxicity which was evident by reduced food consumption/body weight gain of the dams towards the end of gestation and during lactation. However, independently of the primary or secondary nature of the reduced pup weights the magnitude of the growth disturbance suggests that it is unlikely for the pups to make a short-term and full recovery. Thus this effect was considered to be treatment-related and adverse. Regarding pathology, the terminal body weight of the parental females at 12000 ppm was significantly decreased (94%), which was regarded as treatment-related. All findings occurred either individually or were biologically equally distributed about control and treatment groups. They were considered to be incidental and spontaneous in origin and without any relation to treatment.
Under the conditions of the present Reproduction/Developmental Toxicity Screening Test the oral administration of the test item to male and female Wistar rats resulted in signs of systemic toxicity at a concentration of 12000 ppm in female animals. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 12000 ppm for male and 3600 ppm in female Wistar rats. The no observed adverse effect level (NOAEL) for fertility and reproductive performance was 12000 ppm. The NOAEL for developmental toxicity was 3600 ppm, based on lower pup weights at 12000 ppm.