Registration Dossier

Administrative data

Description of key information

There is 28 Day oral dosing study available for 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9, dose level where 250mg/kg/day reduced to 150mg/kg/day , 100mg/kd/day and 30 mg/kg/day.  The no-observed-adverse-effect-level (NOAEL), is regarded as 30 mg/kg/day.  This study has now been followed by an OECD408 90 day oral (gavage) dosing study in rats.  This study which used dose levels of 5, 30 and 150 mg/kg bodyweight, confirmed a 30mg/kg NOAEL despite the longer duration of dosing.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
30 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
This is high quality 90 day study in rats fully compliant with the OECD Guideline 408 and with GLP.

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

Additional information

There is a 90 day oral (gavage) dosing study available for 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9. The dose levelsof 5, 30 and 150 mg/kg bodyweight were selected based on the effects seen in the 28 day study, which were mainly local irritant effects in the stomach, small intestines and foamy macrophages in the mesenteric lymph nodes.

 

The main treatment related effects where limited to the 150mg/kg bodyweight top dose group.

 

There were no macroscopic findings observed at necropsy examination that were considered to be associated with treatment.

 

In addition to some haematological, clinical chemistry and organ weight differences the only histopathological findings were limited to irritant/.corrosive effects in the stomach and small intestines.

 

At 150 mg/kg bw/day histopathological examination showed minimal or mild diffuse epithelial hyperplasia and hyperkeratosis of the forestomach were observed in most animals with minimal or mild focal erosion of the forestomach, minimal or mild submucosal inflammatory cell infiltration, submucosal oedema and minimal focal dyskeratosis being present in the forestomach for a few animals. In addition, minimal to marked foamy macrophages were present in the lamina propria of the small intestine (principally the jejunum but also in the duodenum and ileum) and also in the sinuses of the mesenteric lymph node for both sexes. 

 

At 30 mg/kg bw/day treatment-related changes were restricted to incidences of minimal focal epithelial hyperplasia, minimal focal erosion, submucosal oedema and minimal or mild submucosal inflammatory cell infiltration of the forestomach. No treatment-related changes were observed in the small intestine or mesenteric lymph node.

 

Conclusion.

 

At 150 mg/kg bw/day, the extent of microscopic changes to the fore stomach and gastro-intestinal tract apparent for both sexes was considered to exclude this dosage from being a No Observed Adverse Effect Level (NOAEL). At 30 mg/kg bw/day, microscopic changes were restricted to the fore stomach and were considered to represent a local irritancy effect of the test item rather than systemic toxicity.

 

As such, a dosage of 30 mg/kg bw/day may be considered the NOAEL for systemic toxicity. A dosage of 5mg/kg bw/day was considered to represent the No Observed Effect Level (NOEL).

 

This study was to the current OECD 408 and EU method B26 protocols, with full GLP compliance and with a well-defined test substance so the NOAEL of 30mg/kg/day is a good basis for the calculation of DNEL values for use in Exposure assessments and the chemical safety report

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

This is a full GLP Klimisch 1 study carried out with the substance to be registered to the current OECD408 90 day study in rats guideline and EU B.26.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

The low vapour pressure of the substance means inhalation is not considered to be relevant route of

exposure so no testing is required.  An Inhalation DNEL can be calculated based on the oral NOAEL following REACH guidelines.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:

The low vapour pressure of the substance means inhalation is not considered to be relevant route of exposure so no testing is required.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

The corrosive properties of this substance mean the repeated dose dermal studies are not scientifically justified due to concerns for animal welfare.  A dermal systemic DNEL, based on the oral NOAEL can be calculated following the REACH guidelines.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:

Local effects would be expected to be irritation/corrosion which are local concentration rather than dose dependent. Specific testing is not scientifically justified due to concerns for animal welfare. The classification as corrosive will ensure dermal exposure is well controlled.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: duodenum; digestive: ileum; digestive: jejunum; digestive: stomach

Justification for classification or non-classification

The toxic effects seen can be attributed to oral dosing with a corrosive/irritant test substance which caused effects due to the direct contact with the forestomach and to a much lesser extent the gastrointestinal tract (small intestines). The effects were seen at dose levels in the range of 30 -150mg/kg/day and therefore potentially classifiable as Category 2 (10 -100mg/kg) for specific target organ toxicity after repeated exposure, when based on a 90 day study. However there were no indications of any specific systemic toxic effects such as serious organ damage even at 150mg/kg.  Therefore as the only effects seen at 150mg/kg of 2, 2’-(Octadec-9-enylimino) bisethanol CAS No 25307-17-9 were direct irritant effects, with limited local effects only in the forestomach at 30mg/kg, it does not meet the CLP(GHS) criteria for classification for specific target organ toxicity.