Isostearic acid, esters with methyl α-D-glucoside

Endpoint summary

Description of key information

Oral
Subacute repeat dose study acc. to OECD TG 422
NOAEL, male/female: >= 1000 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

Oral

In a Repeated Dose Toxicity Study according to OECD Test Guidline 422 test substance Isostearic acid, esters with methyl α-D-glucoside in 1 % aqueous carboxymethyl cellulose was administered to 10 male and 10 female Wistar Han rats/dose group by daily oral gavage at dose levels of 0, 50, 150, and 1000 mg/kg bw/day. The males were exposed for 2 weeks prior to mating, during mating, and up to termination (for 30 days). The females were exposed for 2 weeks prior to mating, during mating, post-coitum, and at least 4 days of lactation (for 42 to 44 days).

At 1000 mg/kg bw/day statistically significantly reduced haemoglobin, cholesterol and total protein levels (males), and elevated white blood cell counts (determined for only two females) plus alkaline phosphatase levels (males) were found. Increased liver weights (absolute and relative) were noted for high dose males and females.

No treatment-related changes were noted in any of the remaining parameters investigated in this study (i.e. mortality, clinical appearance, functional observations, body weight, food consumption, macroscopic and microscopic examination).

 

The NOEL is 150 mg/kg bw/day, based on the findings noted at 1000 mg/kg bw/day.

The NOAEL is >= 1000 mg/kg bw/day, based on the findings noted at 1000 mg/kg bw/day which were not considered adverse and were without any corroborative findings like histopathological changes.

 

Dermal

Due to the very low solubility of Isostearic acid, esters with methyl α-D-glucoside in aqueous media dermal uptake and systemic availability was considered to be negligible and therefore an assessment of systemic toxicity via this exposure pathway would not be appropriate. Therefore exposure by oral gavage was considered to be the most appropriate route of exposure for this endpoint.

 

Inhalation

Due to the very low vapour pressure of Isostearic acid, esters with methyl α-D-glucoside inhalation was not considered a relevant route of exposure for this substance. Furthermore, inhalative exposure to aerosols, particles or droplets of an inhalable size at the working place can be excluded. Therefore inhalative exposure was not considered appropriate for a repeat dose study.

Justification for classification or non-classification

The effects observed in this oral repeat dose study according to OECD TG 422 are toxicologically not significant or have not shown treatment-related toxicity.

The effects observed in relation to changes observed for haematological, plasma protein, alkaline phosphatase and cholesterol levels are assessed as adaptive responses as are the changes in liver weights in the absence of overt organ effects.

Therefore no classification according to Directive 67/548/EEC criteria is warranted.

With regard to GHS Regulation EC No 1272/2008 classification requirements for STOT repeat dose, the effects in this oral subacute dose study according to OECD TG 422 are considered NOT to support classification [GHS § 3.9.2.8] due to the absence of significant toxicological effects.