[No public or meaningful name is available]

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral, other

Remarks:

effects observed in a two generation reproduction toxicity study (sub-chronic exposure)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The two substances ADK STAB NA-11 (CAS no. 85209-91-2, EC no. 286-344-4) and ADK STAB NA-70 (CAS no. 85209-93-4, EC no. 458-880-0) have the same molecular structure, i.e. 2,4,8,10-tetra-tert-butyl-6-hydroxy-12H-dibenzo[d,g][1.3.2]-dioxaphosphocin-6-oxide. The substances only differ in the counter ion of the cyclic diarylphosphoric acid ester, i.e. sodium and lithium, respectively. Water solubility of NA-11 amounts to 1850 mg/l, that of NA-70 to 390 mg/l. Both substances dissociate at low concentration in aqueous environments.
With both substances, many toxicity studies were performed to determine their hazard potential. In short-term studies for determination of the hazard potential after single or short-term exposure, i.e. skin and eye irritation, skin sensitisation and systemic toxicity after single oral or dermal application, the two substances did not exhibit adverse effects. The LD50 after single oral or dermal exposure was > 2000 mg/kg body weight. In a study for acute inhalation toxicity performed with NA-70 (in powder form), at high concentrations acute toxicity was observed leading to classification for acute toxicity category 4.
In genetic toxicity tests, the two substances exhibited high cytotoxicity in mammalian cell cultures. Based on the results of in vitro and vivo tests, a genotoxic potential can be excluded. The results from these short-term tests confirm the expectation that the two different salts of the cyclic diarylphosphoric acid ester exhibit well comparable toxic properties.
In oral toxicity studies with repeated dosing, at high doses some toxic effects were observed with both substances. A detailed assessment of all toxicological data available on NA-11 and NA-70 and two other substances with the same chemical structure was performed. It was concluded that read-across from data obtained in studies performed with any of the substances is appropriate including the studies for reproduction and developmental toxicity performed with NA-11. See attached review.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See attached review

3. ANALOGUE APPROACH JUSTIFICATION
See attached review

4. DATA MATRIX
See attached review

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Effect level:

>= 3 000 - < 10 000 mg/kg diet

Based on:

test mat.

Remarks:

When corrected for mean substance intake, the NOAEL of 3000 ppm corresponds to 184-261 mg and 230-286 mg test substance per kg body weight per day for males and females, respectively. From these ranges the NOAEL is set at 200 mg/kg body weight/day.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical biochemistry

clinical signs

food consumption and compound intake

food efficiency

other: food efficiency was strongly depressed in high dose animals; disruption of the gut microbiome by the antimicrobial activity of the test substance is very likely and could have caused the observed (secondary) effects.

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

10 000 mg/kg diet

System:

other: food efficiency was strongly depressed in high dose animals; disruption of the gut microbiome by the antimicrobial activity of the test substance is very likely and could have caused the observed (secondary) effects.

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

no

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subchronic

Species:

rat

System:

other: food efficiency was strongly depressed in high dose animals; disruption of the gut microbiome by the antimicrobial activity of the test substance is very likely and could have caused the observed (secondary) effects.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the NOAEL of 200 mg/kg bw/day derived from the two generation reproduction toxicity study for sub-chronic oral exposure, NA-70 does not need to be classified regarding repeated dose toxicity according to REGULATION (EC) 1272/2008.