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Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

A reproduction/developmental screening test on NX 8000J showed a number of highlighted differences between reproduction values for high dose animals against controls. No one clear reproductive event seems to have been affected to suggest the test material is a reproductive toxicant and therefore this screening study has not shown the test material to significantly affect reproductive and developmental behaviour.

Additional information

In accordance with column 2 of REACH Annex IX, the two-generation reproductive toxicity study does not need to be conducted on the basis of low toxicity seen in the 90 day repeat dose oral study, together with no toxicologically significant effects seen in the reproductive/developmental toxicity screening study. In addition, there will be no significant exposure to the substance during its life cycle.

Effects on developmental toxicity

Additional information

In accordance with column 2 of REACH Annex IX, the pre-natal developmental toxicity study does not need to be conducted on the basis of low toxicity seen in the 90 day repeat dose oral study, together with no toxicologically significant effects seen in the reproductive/developmental toxicity screening study. In addition, there will be no significant exposure to the substance during its life cycle.

Toxicity to reproduction: other studies

Additional information

In an Oral (dietary) reproduction/developmental toxicity screening test in the rat (OECD 421, 1995) Experimental Additive 20735-82was administered to three groups each of ten male and ten female Wistar Han:HsdRccHan:WIST strain rats in dietary admixture at dose levels of 20000, 5000 and 250 ppm (equivalent to a mean dosage of 1165, 296 and 14 mg/kg/day for males and 1533, 411 and 20 mg/kg/day for females). 

In summary there were a number of highlighted differences between reproduction values for high dose animals against controls. The background control data for this strain of animal has been provided in the endpoint study summary. It should be of note that the high dose level of 20000 ppm equated to a test material intake of above 1000 mg/kg particularly during lactation for females. The test material showed no significant evidence of toxicity to adult animals but the volume of chemical intake may well have impacted upon the nutritional intake from the diet consumed thereby providing less than optimal conditions for females during pregnancy and early lactation.

 

The administration of this test material at dose levels above 1000 mg/kg intake by dietary inclusion showed the material to be of low toxicity to the adult. Because test material intake increased significantly during pregnancy and lactation this may have contributed to the minor differences in reproduction parameters measured. The failure to mate or conceive was seen in isolated individuals. These events do occasionally occur as a spontaneous event and because it was seen in one individual for each of the categories it cannot be considered a convincing effect of treatment. Minor changes in corpora lutea counts, implantation numbers and post implantation loss values are not conclusive evidence of a specific reproductive effect when considered in isolation. Collectively, these findings together with the slight reduction in female offspring weight gain during the first four days of lactation may well reflect minor fluctuations in reproductive performance as a consequence of elevated body burden of test material above 1000 mg/kg day. No one clear reproductive event seems to have been affected to suggest the test material is a reproductive toxicant and therefore this screening study has not shown the test material to significantly affect reproductive and developmental behaviour.

Justification for classification or non-classification

A total of four dietary repeat dose studies have been performed on NX8000. The studies have been performed in both Sprague-Dawley and Wistar rats in 3 different facilities in the UK, Japan and China. Three of the studies were full studies performed according to, or were similar to, the relevant OECD test guideline. Three of the studies provided unequivocal conclusions that the test item was not toxic, either in terms of general toxicity or for reproductive and developmental toxicity, according to the limitations

of the protocol design. One of the studies was a screening study design (OECD 421), and in this study the results may be described as equivocal for reproductive toxicity but clearly non-toxic for general and developmental toxicity. The minor effects that were noted were not statistically significant and nor were they outside of the range for the relevant historical control data for the laboratory.

Please refer to the attached report "NX8000 Reproductive Toxicity - Brief Review of the Data and Expert Opinion".

Based on the available data from the screening study it is not considered justifiable to classify the substance for reproduction/developmental toxicity according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.