Registration Dossier

Administrative data

Description of key information

A waiver under REACH Annex XI 1.5 is being claimed based upon a “similarity” of “(1) a common functional group” as stated in the Legislation. 
It is intended that read across from vinyl neononanoate will be used to fill the 90-day repeat dose end point after the test plan for vinyl neononanoate has been approved and the testing completed. Supporting data from an 28-day oral OECD 422 and a 90-day inhalation OECD 413 on vinyl neodecanoate will be used as weight of evidence. A virtually identical 14-day study in vinyl neononanoate will be also be used to validate read across. The results of this testing will be evaluated in conjunction with existing data for this substance, and read-across will be applied to vinyl 2-ethyl hexanoic acid if the 90 day study data is not inconsistent with existing results for a 14 day repeated dose study on this Registered substance
In a GLP rat 14-day range finder oral gavage study the dose levels were 0, 50, 200, 1000, and 2000 mg/kg/day. Due to mortality at the high dose and pathological and hematological findings at the 1000 mg/kg/day dose the NOAEL was determined to be 200 mg/kg/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
200 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
500 mg/m³

Additional information

Hereafter is a summary of all repeat dose toxicity studies related to vinyl 2 -ethylhexanoate including read across from vinyl neodecanoate and vinyl neononanoate.

 

Read across from vinyl neononanoate will be used to fill the 90-day repeat dose end point when the test plan for vinyl neononanoate has been approved and completed. Read across will be further evaluated when the study is complete.

 

In a GLP rat 14-day range finder oral gavage study the dose levels were 0, 50, 200, 1000, and 2000 mg/kg/day. Due to mortality at the high dose and pathological and hematological findings at the 1000 mg/kg/day dose the NOAEL was determined to be 200 mg/kg/day. Data from this study, among others, was used to support the use of read across from vinyl neononanoate to vinyl 2-ethylhexanoate. The NOAEL in this study was 200 mg/kg/day while a NOAEL from the 14-day for vinyl neononanoate was 200 mg/kg/day. This was supporting evidence that the data from vinyl neodecanoate can be read across to vinyl 2-ethylhexanoate.

 

In a rat O.E.C.D. 422 28-day oral gavage study on vinyl neodecanoate the dose levels were: 0, 100, 250 and 1000 mg/kg/day. No adverse findings were made for female rats at any dose level. Male rats had significantly elevated liver weights relative to the control at 250 and 1000 mg/kg. However, this finding is considered to be due to an adaptive metabolic response to test substance. No abnormal histopathological findings were made male rat liver sections. Male rat blood urea nitrogen (BUN) was significantly increased at 1000 mg/kg. Histopathological examination found male rat kidney nephropathy and accumulation of alpha-2-u-microglobin only at the high dose. These findings are indicative of male rat specific nephropathy that is not relevant to human health.

 

Rats were exposed to nominal concentrations of Vinyl Neodecanoate of: 0. 0.25, 0.50 and 1.0 gm/m3 for 6 hr/day for 90 days by vapor inhalation. Significant adverse findings were: reduced male body weight gain at 1.0 gm/m3; elevated female liver weight at 0.50 and 1.0 gm/m3; elevated male rat liver and kidney weights at 1.0 gm/m3 and elevated male serum alkaline phosphatase at 1.0 gm/m3. No adverse histopathological findings were made.

 

The 90-day rat inhalation study is the most appropriate study for estimating a systemic effect long-term Worker and General Population DNEL for Vinyl Neodecanoate. The NOAEC for this study based on male rat weight decrement, increased liver and kidney weights and alkaline phosphatase levels at the high dose is 500 mg/m3 or approximately 62 ppm.

 


Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; neurologic: central nervous system; urogenital: kidneys

Repeated dose toxicity: inhalation - systemic effects (target organ) digestive: liver; urogenital: kidneys

Justification for classification or non-classification

Criteria of EU Directive 67/548/EEC and the CLP (Directive 1272/2008) for systemic target organ Classification and Labeling were not met by Vinyl 2 -ethylhexanoate.