Octasodium 2-(8-(4-chloro-6-(3-((4-chloro-6-(3,6-disulfonato-2-(1,5-disulfonatonaphthalen-2-ylazo)-1-hydroxynaphthalen-8-ylamino)-1,3,5-triazin-2-yl)aminomethyl)phenylamino)-1,3,5-triazin-2-ylamino)-3,6-disulfonato-1-hydroxynaphthalen-2-ylazo)naphthalene-1,5-disulfonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

None

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

The substance is not considered to pose a hazard to reproduction based on the findings of read across to the 1 -generation study on an analoguous material. The study results on the analogue indicate that the main treatment related finding was colouration of the rats by the test substance. Blue colouration was evident on the coat and skin and in the oral cavity of rats of all treatment groups. There was no evidence of an effect of H112323 on the bodyweight of rats at dose levels up to and including the highest dose level, nor was there evidence of an adverse effect of H112323 on bodyweight during gestation or lactation.

 

On reproductive performance, the pre-coital interval was 1-4 days in the majority of pairings and there was no evidence of an effect of administration of H112323. The length of gestation was not affected by administration of H112323. The number of animals successfully mating was satisfactory in males and females in all groups and there was no evidence of an effect of H1123233.

 

The number of whole litter losses was 6, 2, 3 and 4 in the control, 1000, 5000 and 20000ppm dose groups respectively The percentage of pups live born was 97% or greater in all groups and was unaffected by administration of H112323.

 

Kidney weights were increased in both sexes receiving 20000 and 5000ppm. However the difference from control was only statistically significant in females at the 5000 ppm dose level Testes weights were slightly increased in males receiving 20000ppm, There was no evidence of an effect on epididymis weight in any dose group.

 

A number of rats died or were killed intercurrently. The findings were varied and apart from test substance colouration were not clearly treatment related.

 

At termination there was a treatment related increase in the severity of tubular basophilia in the kidneys, Slight or moderate lesions were present in males at 20000 and females at 20000 and 5000ppm. Although minimal degrees of this change were not present in the designated control rats at termination an incidence of one rat from the infertile group was observed in males. The single incidence of minimal tubular basophilia observed in a female at 1000ppm is therefore considered not to be treatment related. There were no other treatment related findings and no findings which correlated with the macroscopically observed blue discolouration or dark appearance of internal organs.

 

Of the rats considered to be infertile or suspected infertile, a number of findings were present to explain the infertility in some rats including dystocia, endometritis, vaginitis, or imperforate vagina. However in the majority of rats no pathological change was observed to explain the reproductive failure. There were no treatment related findings observed in these rats with the possible exception of two female rats dosed at 20000ppm with slight tubular basophilia.

 

Offspring

 

The only treatment related clinical observations were attributable to colouration or staining of the test substance. This was evident in the nostrils and on the skin or coat of the majority of offspring. Male and female pup bodyweights were similar in control and treated groups. Apart from colouration by the test substance there was no evidence of treatment related findings in those pups which were found dead or killed for humane reasons and were examined macroscopically.

 

The following information is taken into account for any hazard / risk assessment:

Oral, inhalation and dermal acute toxicity are all considered.

Value used for CSA:

NOEL: 1000 mg/kg bw (as 20000 ppm in feed)

Short description of key information:
A discussion of reproductive effects is provided.

Effects on developmental toxicity

Description of key information

Not conducted.

Additional information

No assessment of developmental hazard has been undertaken at this tonnage threshold. This is due to the following considerations:

 

1) The substance was not found to be harmful to reproductive processes in the 1-generation reproduction study discussed above. No abnormalities of offspring was also noted in this study.

 

2)The substance was negative in three separate in vitro mutagenicity assays, and did not have any effects at the highest dose thresholds noted.

3) Repeat-dose studies with oral treatment in rats did not reveal any tumorigenic properties which could be related to the administration of the test substance. No treatment related effects were noted in the sperm parameters investigated in the 90 -day study. Consequently, the substance is considered not to have the potential to cause teratogenic effects.

As such, on animal welfare grounds it is not considered appropriate to conduct a further developmental screening test at this level of registration, as the evidence indicates that there is no associated potential teratogenic effect associated with the substance. 

Justification for classification or non-classification

The above study has been ranked reliability 1 according to the Klimish et al system. This ranking was deemed appropriate because the study was conducted to GLP and in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.