Registration Dossier

Administrative data

Description of key information

There are two 90 day studies available, for the read across substance registered under 2,2’-(C16-18 (even numbered, C18 unsaturated) alkyl imino) diethanol CAS No 1218787-32-6. While these studies are from 1965 and less detailed than current studies, they are considered to be Klimisch 2.  Due to problems with vomiting in the dog study the rat study provides the most reliable repeat dose NOAEL

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
35 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
There are two 90 day studies available, for the read across substance registered under 2,2’-(C16-18 (even numbered, C18 unsaturated) alkyl imino) diethanol CAS No 1218787-32-6. While these studies are from 1965 and less detailed than current studies, they are considered to be Klimisch 2. Due to problems with vomiting in the dog study the rat study provides the most reliable repeat dose NOAEL.

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

The 90 Day dog study, where the dogs were dosed by mixing a solution of the test substance in maize oil into the dry dog diet, suffered from serious problems with acceptance of the diet. This was due to corrosive/irritant nature of the test substance. The highest dose level of 120mg/kg/day vomited 2 to 3 hours after feeding and then began to refuse their food. Despite attempts to acclimatise them to the test substance this group had to be terminated after 5-6 weeks due to their poor condition, with 20% bodyweight loss. There was also sporadic vomiting and reluctance to eat all their food in the 40mg/kg/day group. This left the 13 mg/kg/day group as the NOAEL. In the 90 day rat study which some decrease in food consumption was evident at the higher dose levels the 500ppm in the diet level was a clear NOAEL. This was calculated to be ca. 35 mg/kg/day. Due to these problems with vomiting and reduced food consumption etc. in the dog study, the NOAEL from the rat study has been selected as being more reliable. This is supported by the findings of no clear systemic toxicity in either study, the effects seen in both studies be associated with local irritant effects in the gastrointestinal tract. The 35mg/kg/day NOAEL value will therefore be used for key value for the chemical safety report for read across to,2’-(C16-18 (evennumbered), alkyl imino) diethanol CAS No 1218787-30-4.

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

There are no repeat dose studies on,2’-(C16-18 (evennumbered), alkyl imino) diethanol CAS No 1218787-30-4.  But there are two 90 day oral toxicity studies for the read across substance Ethanol, 2,2’-iminobis-, N-tallow alkyl derives CAS No 61791-44-4 registered under 2,2’-(C16-18 (even numbered, C18 unsaturated) alkyl imino) diethanol CAS No 1218787-32-6.  There is a 90 day dietary study in rats and a 90 Day study in dogs where the test substance was added to the diet in a solution in maize oil.  The Dog study was dosed at 13, 40, 120 mg/kg/day with a maize oil vehicle control.  The rats were feed diets containing 170, 500, 1’500 and 4’500ppm of the tests substance.  Both studies provide NOAEL values.  These studies were carried out in 1965, but are sufficiently well documented including information on the test substance to be considered suitable for use for REACH. Due to issues with sporadic vomiting and anorexia in the dog study, the data from the rat study will be used as the 90 day NOAEL.

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

We have no repeat dose inhalation study for 2, 2’-(C16-18 (evennumbered), alkyl imino) diethanol CAS No 1218787-30-4, however it is a waxy solid with a low vapour pressure 0.73 mPa at 20ºC (1.2 mPa at 25ºC), significant exposure to vapours would not be expected at ambient temperatures so it is considered to not be scientifically valid to conduct a repeat dose inhalation study.  Also the irritant nature of the substance would also make this difficult to perform for animal welfare reasons.  The guidance for REACH allows the inhalation long term DNELS to be calculated for the oral repeat dose NOAEL.

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

We have no study for repeat dose local inhalation effects for 2, 2’-(C16-18 (evennumbered), alkyl imino) diethanol CAS No 1218787-30-4, however it is a waxy solid with a low vapour pressure 0.73 mPa at 20ºC (1.2 mPa at 25ºC), significant exposure to vapours would not be expected at ambient temperatures so it is considered to not be scientifically valid to conduct a repeat dose inhalation study.  Also the irritant nature of the substance would also make this difficult to perform for animal welfare reasons.  The low possibility of inhalation makes such a test scientifically unjustified.

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

Due the 2, 2’-(C16-18 (evennumbered), alkyl imino) diethanol being considered to be irritating to skin, it is not possible to conduct repeat dose dermal toxicity studies due to animal welfare considerations.  Also it is considered very unlikely that dermal absorption would exceed oral absorption, so it would be expected than the oral NOAEL would be lower than the from a dermal study.  Data from the repeat dose oral studies can be used in the setting of DNELs.

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

2, 2’-(C16-18 (evennumbered), alkyl imino) diethanol is classified as a skin irritant, risk management measures such as wearing appropriate gloves and protective clothing will prevent an significant dermal contact.  Local effects on the skin would be expected to be limited to local irritation, which would be dependent on the local concentration rather than the dose or duration of exposure.  This is a medium hazard and does not justify the requirement for an additional dermal animal study to establish a local NOAEL for dermal exposure.

Justification for classification or non-classification

The NOAEL in the 90 day dog study of 35mg/kg/day was for gavage dosing. Specific Traget Organ effects were only seen in the 15000ppm (ca.105mg/kg/day group) and higher groups. The EU CLP (GHS) criteria for classification for Specific Target Organ Toxicity (STOT) are based on data from a 90 day study, for Category 2 the range for such effects is 10-<100 mg/kg/day. As only limited signs of specific target organ toxicity in the gastrointestinal tract were see at higher than 100mg/kg bw/day and there is no evidence of specific target organ toxicity below the 100mg/kg bw/day threshold, therefore there is no requirement for a classification for STOT Category 2 under the EU CLP (GHS) criteria.