Registration Dossier

Administrative data

Description of key information

No acute toxicity data are available. Assessment was based on a read-across with primary alkylamines showing a low acute toxicity as follows :

- C16-18 -(even numbered) –alkylamines (common name N-hydrogenated tallow alkyl amine; new CAS 90640-32-7 ; former CAS 61788-45-2) : LD50 oral rat > 5000 mg/kg

- C12-18 coco alkylamine (new CAS 130169-56-1 ; former CAS 61788-46-3 ; other former CAS 68155-27-1) : LD50 dermal rat > 2000 mg/kg

No inhalative study is available but limited exposure is expected.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Pemberley Rabbits, Cottenham, Cambridgeshire
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: 2.0 to 2.2 kg
- Housing: individual housing in metal cages
- Diet (e.g. ad libitum): SDS Standard Rabbit Diet; ad libitum
- Water (e.g. ad libitum): tap water; ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 19
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 19
- Photoperiod (hrs dark / hrs light): 12/12 (19:00-7:00 / 7:00-19:00)
Route of administration:
oral: gavage
Vehicle:
other: methyl cellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 % (w/v) suspension in 1% methyl cellulose

MAXIMUM DOSE VOLUME APPLIED: 10 mL

Doses:
5000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations daily; weighing on day 1, 8 and 15
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities throughout study
Clinical signs:
Pilo-erection, hunched posture, diarrhoea
Body weight:
slightly reduced on day 8 but normal by day 15
Gross pathology:
no abnormal findings
Other findings:
no abnormal findings
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Based on the findings of this limit test, the acute median lethal dose (LD 50) of Lilamin AC-HBG/P after a single dose to rats was greater than 5000 mg/kg body weight
Executive summary:

In an GLP compliant OECD TG 401 study, the test material Lilamin AC-HBG-P (hydrogenated tallow alkyl amine), a white granular solid (purity 95%), was orally applied to Wistar rats at a dose of 5000 mg/kg bw. The substance was applied as a 50% suspension in 1% methylcellulose (limit-test). There were no deaths, hence, the LD50 exceeded 5000 mg/kg. Clinical signs were diarrhea, piloerection, hunched posture, abnormal gait and pallor of extremities. Complete recovery from these clinical signs was observed by day 5. Body weights were initially reduced but body weight gain was not different from controls by the end of the study (day 15). No treatment-related effects were observed at necropsy. Based on the findings of this study, the acute median lethal dose (LD 50)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study similar to Guideline but only 4 animals (2 males/2females) per dose group used
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
only 4 animals per dose group used
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: CFY
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Interfauna UK Limited, Huntingdon, Cambridgeshire, UK
- Age at study initiation: approx. 6 - 8 weeks
- Weight at study initiation: 200 - 245 g
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The compound was administered either unchanged at a volume of 0.63 mL/kg (= 500 mg/kg) or in water at a volume of 5 mL/kg (=2000 mg/kg).
Since the compound is described as corrosive and dermal irritative reactions were noted in the 500 mg/kg group (undiluted test material), dilution
for testing of the acute dermal toxicity at 2000 mg/kg bw is justifiable.

TEST SITE
- Area of exposure: 10% of total body surface
- % coverage: 100
- Type of wrap if used: occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.63 ml/kg (undiluted, 500 mg/kg group); 5 ml/kg (40% solution, 2000 mg/kg group)
- Concentration (if solution): 40% in water (only for 2000 mg/kg dose group)

VEHICLE
- water (only for 2000 mg/kg dose group)
Duration of exposure:
24h
Doses:
500 mg/kg bw (undiluted)
2000 mg/kg bw (diluted to 40% w/v in water)
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occured during the study.
Clinical signs:
500 mg/kg/bw: no clinical signs throughout observation period
2000 mg/kg/bw: hunched posture, abnormal gait (waddling), lethargy, and decreased respiratory rate (shortly after treatment, free of symptoms
thereafter)
Body weight:
Bodyweight losses were recorded on day 4 for one male and two females dosed at 500 mg/kg bw and two females dosed at 2000 mg/kg bw. Body weight gains were recorded for all other rats on day 4 and for all rats on days 8 and 15.
Gross pathology:
Terminal autopsy revealed slight bruising in the subcutaneous tissue of one male and one female rat dosed at 500 mg/kg bw and scab formation with or without ulceration was seen in all rats dosed at 2000 mg/kg bw.
An area of minimal congestion of the stomach (mucosal aspect) was seen in one female rat dosed at 2000 mg/kg bw.
Other findings:
Dermal reactions:
necrosis in all rats dosed at 500 mg/kg bw, persisting until day 12
well defined to moderate oedema in rats dosed at both levels
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute lethal dermal dose (LD 50) of Amine KK to rats was greater than 2000 mg/kg body weight
Executive summary:

In a GLP-compliant study similar to OECD TG 402, the test compound Amine KK (cocoalkylamine), a yellow liquid (purity 100%), was dermally applied under occlusion to Sprague-Dawley rats. At a dose level of 500 mg/kg body weight, the test material was applied undiluted (application volume 0.63 ml/kg bw), at a dose level of 2000 mg/kg bw the substance was diluted to a 40% solution (w/v) in distilled water (application volume 5 ml/kg). Compared to a regular OECD TG 402 study a reduced number of animals was used (4 instead of 5 animals/dose). There were no mortalities, hence, the LD50 is > 2000 mg/kg bw. No clinical signs were observed at 500 mg/kg bw. At 2000 mg/kg, hunched posture, abnormal gait, lethargy and decreased respiratory rate were noted. Signs of dermal reactions at the application site of both treatments were well defined to moderate oedema until days 4-5. Hard scabs, persisting to the end of the observation period, frequently prevented the assessment of oedema

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Read across with a GLP study.

Additional information

There are no human data on acute toxicity for hydrogenated tallow alkylamines nor for any of the other primary alkylamines considered a chemical category with respect to chemical safety assessment. In animals, data for all relevant exposure routes are available.

Oral:

Studies for the oral route are available for hydrogenated tallow alkylamines as well as for all other category members of primary alkylamines. For hydrogenated tallow alkylamines a LD50 of greater 5000 mg/kg body weight was established. Comparable LD50 values indicating moderate acute oral toxicity were revealed also for tallow alkylamines and octodecenylamines. This view of only moderate toxicity was also taken in the existing EU risk assessment of primary alkylamines.

Inhalation:

There is no study on inhalation toxicity available for the registered substance.

REACH stipulates that testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. REACH guidance R.7.a, chapter. 7.4 Acute toxicity, indicates that in principle no inhalation studies are needed when vp < 0.1 Pa at 20°C or particle size > 100 µm. The registered substance is a solid (scales) with no expected inhalable particles and a vapour pressure less than 10-6 Pa at 20°C. Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur, and no acute inhalation test was performed. In addition, considering the apparently low systemic toxicity of the primary alkylamines, no need for further inhalative testing was seen.

 

There is no risk for aspiration, the registered substance is a solid upon ingestion.

 

Dermal:

There is no dermal LD 50 value for acute skin toxicity of the registered substance. Acute toxicity by oral route resulted to a LD50 cut-off value of 2500 mg/kgbw indicating relative low acute systemic toxicity for which no classification is required. Considering the apparently low systemic toxicity of the primary alkylamines, no need for further dermal testing was seen. In addition, a read-across can be made with C12 -18 -(even numbered)-alkylamines for which a dermal acute toxicity study performed in rat is available and demonstrated also a low acute toxicity (LD50 > 2000 mg/kg body weight).

 


Justification for classification or non-classification