Sodium 3-(2H-benzotriazol-2-yl)-5-sec-butyl-4-hydroxybenzenesulfonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

A reproduction/developmental toxicity screening test of Tinogard HS was conducted in rats by oral gavage. The study was based on the following guidelines: 1) OECD 421, Reproduction/Developmental Toxicity Screening Test, July 1995. 2) OPPTS 870.3550, Reproduction/Developmental Toxicity Screening Test, July 2000. The doses of 0, 50, 200 and 800 mg/kg body weight/day (bw/d) as dose levels where chosen based on an available 28 -day study. Rats of the control group received the vehicle, 1% Aqueous carboxymethyl cellulose, alone. After acclimatization, four groups of ten male and ten female Wistar Han rats were exposed by oral gavage to the test substance at 0, 50, 200 and 800 mg/kg body weight/day. Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 43-55 days, i.e. during 2 weeks prior to mating, during mating, during postcoitum, and during at least 4 days of lactation. The following parameters were evaluated: mortality / viability, clinical signs, body weights, food consumption, reproduction/developmental parameters, pup observations, macroscopy, organ weights, and histopathology. Chemical analyses of formulations were conducted once during the study to assess accuracy, homogeneity and stability.

Accuracy, homogeneity and stability of formulations were demonstrated by analyses. Parental results: Salivation was noted for all animals at 800 mg/kg bw/d and higher water consumption was also noted for both sexes. These findings may be related to each other, and increased water consumption may have been a secondary response to the salivation. In the absence of any other toxicologically relevant findings, the salivation and higher water consumption were considered treatment-related but not toxicologically significant. No parental toxicity was observed up to the highest dose level tested (800 mg/kg bw/d) for any of the remaining parental parameters investigated in this study (i.e. body weight, food consumption, clinical laboratory investigations, macroscopic examination, organ weights, and microscopic examination).

Reproductive results: No reproduction toxicity was observed up to the highest dose level tested (800 mg/kg bw/d) for any of the reproductive parameters investigated in this study (i.e. mating, fertility and conception indices, precoital time, and numbers of corpora lutea and implantation sites).

Developmental results: No developmental toxicity was observed up to the highest dose level tested (800 mg/kg bw/d) for any of the developmental parameters investigated in this study (i.e. gestation index and duration, parturition, maternal care and early postnatal pup development consisting of mortality, clinical signs, body weight and macroscopy).

Based on these results, a parental, reproduction and developmental No Observed Adverse Effect Level (NOAEL) of 800 mg/kg bw/day was determined. A parental No Observed Effect Level (NOEL) of 200 mg/kg bw/day was determined based on salivation and increased water consumption noted for animals at 800 mg/kg.

Short description of key information:
NOAEL (fertility) > 800 mg/kg bw/day (NOTOX, 2011)

Effects on developmental toxicity

Description of key information

NOAEL (developmental toxicity) > 800 mg/kg bw/day (NOTOX, 2011)

Additional information

No signs of developmental toxicity or teratogenicity were observed in a screening study according to OECD 421 guideline up to the highest dose tested (800 mg/kg bw/day).

Justification for classification or non-classification

Based on a screening stuy according to OECD 421 guideline, the test item was not classified and labelled according to Directive 67/548/EEC (DSD) and to Regulation /EC) No 1272/2008 (CLP).