Phenol, 2,4-dinitro-, sulfurized, leuco derivatives

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

In a repeated dose toxicity study with reproduction/developmental toxicity screening according to OECD guideline 422 and GLP Leuco Sulfur Black 1 was administered by gavage to groups of 10 rats per sex and dose at 0, 100, 300 and 1000 mg/kg bw/d. Male rats were treated for 29 days, female rats for 14 days prior to pairing, though the pairing and gestation periods until the F1 generation had reached day 4 post partum. The test item was administered in water as vehicle at a dose volume of 10 mL/kg bw/d. Control animals were doses with the vehicle alone.

Observation and examinations consisted of mortality, clinical signs, detailed clinical observations, food consumption, body weight, functional observation battery, clinical biochemistry, haematology, urinalysis, macroscopical examination at necropsy, organ weights and histopathological examination of organs. Reproductive parameters examined were examination of reproductive organs with special emphasis on the stages of spermatogenesis and histopathology of interstitial cell structure, mating performance and fertility, duration of gestation, implantation sites, pre- and post-implantation loss, corpora lutea count. Parameters relevant for developmental toxicity consisted of litter size, number of live and dead pups, sex ratio, pup weight at day 4 post partum, macroscopical examination of pups at termination.

The only effect seen was a dark discolouration of faeces in all high dose animals starting on day 3 of the study and lasting until termination. Based on this finding a NOAEL of 1000 mg/kg bw/d was derived for general toxicity as well as for reproductive and developmental toxicity.

 

The discolouration of faeces was the only effect observed in this study and also in the acute oral toxicity study. Organs or urine were not discoloured and signs of substance deposits were not found in histopathological analysis of the organs. This indicates that Leuco Sulfur Black 1 is directly excreted and that absorption in the gastrointestinal tract does not occur following oral administration.

 

The mean molecular weight and number-average molecular weight (Mn) of Leuco Sulfur Black 1 is > 8000 Da. It is very poorly or even not soluble in common polar and non-polar solvents such as water (solubility of 62.4 mg/L), DMSO, methanol, DMF, THF, chloroform and not soluble in acid likes sulfuric acid and trifluoroacetic acid. The vapour pressure of the pure substance, calculated from the boiling point of > 400 °C, is 1.8 x 10E-5 hPa at 25 °C. These substance properties supported by the results of oral toxicity studies demonstrate that the absorption of Leuco Sulfur Black 1 via the oral, dermal or inhalation route and, consequently, systemic bioavailability is negligible.

 

Based on the substance properties and the fact that no toxicity was seen in any of the tests it is concluded that exposure to Leuco Sulfur Black 1 does not raise any health concern. In line with Regulation (EC) No 1907/2006 Annex XI and taking into account the REACH paradigm that new tests on vertebrates shall only be conducted or proposed as a last resort when all other data sources have been exhausted, further animals studies to examine the reproductive and developmental toxicity of Leuco Sulfur Black 1 are not necessary and should not be performed.

Short description of key information:
Leuco Sulfur Black 1 did not cause any toxic effects in the repeated dose toxicity study with reproduction/developmental toxicity screening in rats (OECD 422). The limit dose of 1000 mg/kg bw/d was derived as NOAEL for general parental toxicity and reproductive/developmental toxicity.

Effects on developmental toxicity

Description of key information

Leuco Sulfur Black 1 did not cause any toxic effects in the repeated dose toxicity study with reproduction/developmental toxicity screening in rats (OECD 422). The limit dose of 1000 mg/kg bw/d was derived as NOAEL for general parental toxicity and reproductive/developmental toxicity.

Additional information

see "effects on fertility"

Justification for classification or non-classification

Based on the available data Leuco Sulfur Black 1 is not subject to classification and labelling according to Directive 67/548/EECand Regulation 1272/2008/EC.