Reaction mass of 1,2-Benzenedicarboxylic acid, 4-sulfo-, trisodium salt, 1,2-Benzenedicarboxylic acid, 3-sulfo-, sodium salt (1:3), Sodium sulphate

Endpoint summary

Description of key information

OECD 422 (Harlan, 2013): NOAEL = 1000 mg/kg (systemic and local)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Produkt SPS was administered to male rats for 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum in a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test. The study was conducted according to OECD 422 guideline and GLP (Harlan, 2013).

The following dose levels were applied:

Group 1: 0 mg/kg body weight/day (control group)

Group 2: 100 mg/kg body weight/day

Group 3: 300 mg/kg body weight/day

Group 4: 1000 mg/kg body weight/day

A standard dose volume of 10 mL/kg body weight with a daily adjustment to the actual body weight was used. Control animals were dosed with the vehicle alone (Milli-Q-Water).

The following results were obtained:

Parent Animals:

General Tolerability

All animals survived until scheduled necropsy. No clinical signs were noted in males and females at any dose level.

Food Consumption and Body Weights

No adverse effects on mean food consumption and mean body weights of males and females were observed at any dose level.

Clinical Laboratory Investigations

No test item-related findings were noted during the clinical laboratory investigations.

Reproduction and Breeding Data

Mean precoital time, fertility index and conception rate were not affected by the treatment with the test item. No effects on implantation loss or postnatal loss were observed.

Organ Weights

No effects on organ weights were noted in any group.

Macroscopical Findings and Histopathological Examinations

There were no test item-related macroscopical or microscopical findings in any group.

Litter Data - F1 Pups

Findings at First Litter Check and during Lactation

The mean number of pups at first litter check was not affected by the treatment with the test item. The sex ratio was also not affected. No abnormal pup was noted at any dose level.

Pup Weights to Day 4 Post Partum

No effects on pup weight and pup weight gain were observed.

Macroscopical Findings

At necropsy of pups, there were no abnormal findings.

Conclusion

Based on these results the NOAEL (No Observed Adverse Effect Level) for general and reproductive toxicity was considered to be 1000 mg/kg body weight/day.

Range-Finder:

A non-GLP non-guideline 14-day oral gavage study was performed (Harlan, 2012) to select suitable dosages of Produkt SPS to be used in the subsequent combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in the rat. Two groups of 4 male and 4 female Han Wistar rats were treated by gavage with Produkt SPS once daily over a period of 14 days at dose levels of 300 and 1000 mg/kg body weight/day. A standard dose volume of 10 mL/kg body weight was used. Control animals (0 mg/kg bw/day) were dosed with the vehicle alone (Milli-Q-Water). No deaths occurred during the study. No clinical signs were observed during the study at any dose level. No effects on mean food consumption and mean body weight were noted. The assessment of hematology and clinical biochemistry data did not reveal any test item-related effects in males and females. No effects on organ weights were noted. No macroscopical findings were noted at any dose level. Based on these observations, dose levels of 100, 300 and 1000 mg/kg bw/day were considered appropriate for the subsequent Reproduction/Developmental Toxicity Screening Test in the Han Wistar Rat.

Justification for classification or non-classification

Based on the available data, the test substance is not classified with regard to repeated dose toxicity according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP), respectively.