Propanol, iminobis-, N-(C16-18 and C18-unsatd. alkyl) derivs.

Endpoint summary

Description of key information

No acute oral toxicity studies are available for the substance but for the read across source substance there is an acute oral toxicity study, of which is validity 1, with addtional supportive data.  In the study considered most relevant to the classification of this substnace the LD50 values (plus 95% confidence limits) were LD50 of 1260 (1053 - 1508) mg/kg body weight. Based on a mean vlaue 1260mg/kg will be used for classification etc.

LD50 = 1260 mg/kg bw.

The only study available is an oral LD50 study on 2,2'-(Octadec-9-enylimino)bisethanol  CAS No 25307-17-9, the study is reliability 1 GLP compliant to OECD Guideline 401.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

November-December 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Complete report according to guidelines/standards.

Justification for type of information:

See section 13.2 for the read-across justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Sprague-Dawley CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna (UK) Ltd., Wyton, UK
- Age at study initiation: 5-8 weeks
- Weight at study initiation: 123-152 g (males), 120-146 g (females)
- Fasting period before study: overnight prior to dosing until ca. 2 hours after dosing
- Housing: 5/sex in solid floor polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 45-65
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 7 November To: 10 December 1986

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: neat test compound was used

MAXIMUM DOSE VOLUME APPLIED: 2.20 ml/kg bw

Doses:

1000, 1260, 1587, 2000 mg/kg bw

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: observations were made 1 and 4 h after dosing and once daily thereafter. BW were
measured weekly and at death
- Necropsy of survivors performed: yes

Statistics:

Method of Weil CS, Biometrics (1952), 8, 249

Preliminary study:

A preliminary study was carried out using 2 groups of one male and one female each. Dose levels were 500 and 2000 mg/kg bw.
At 500 mg/kg the 2 animals survived, whereas both animals died at 2000 mg/kg bw.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 260 mg/kg bw

95% CL:

1 053 - 1 508

Sex:

male

Dose descriptor:

LD50

Effect level:

1 309 mg/kg bw

95% CL:

1 024 - 1 674

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 1 587 mg/kg bw

Mortality:

All deaths occurred 2-3 days after treatment.

Clinical signs:

other: Major signs of toxicity noted in all dose groups during the day of dosing were hunched posture, pilo-erection, decreased respiratoryrate, increased salivation and ptosis. Surviving animals treated with 1000 mg/kg continued to show signs of toxicity on day

Gross pathology:

Common abnormalities noted at necropsy of decedents were congested or abnormally red lungs, dark livers, haemorrhage of the
gastric mucosa and congestion of the small intestines. Necropsy of animals killed at the end of the study revealed scattered
white thickened or raised areas on the non-glandular region of the stomach. The liver of two animals treated with 2000 mg/kg was adhering to the stomach. One decedent treated with 1000 mg/kg and two animals treated with 1587 mg/kg were cannabalised. No
necropsy was performed.

Other findings:

No data

Mortality data

Dose level (mg/kg bw)	Deaths
	Male	Female	Total	%
1000	0/5	1/5	1/10	10
1260	3/5	3/5	6/10	60
1587	4/5	4/5	8/10	80
2000	3/5	4/5	7/10	70

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The LD50 value was calculated to be 1260 mg/kg bw with 95% confidence limits of 1053 and 1508 mg/kg bw. The test compound was classied in Category IV according to OECD-GHS.

Executive summary:

A study was performed to determine the acute oral toxicity of the test material in the Sprague-Dawley CFY strain rat. The study was designed to comply with the recommendations of the OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity". Following a range-finding study, four groups, each of ten fasted animals (five males and five females) were given a single oral dose of undiluted test material, at dose levels of 1000 to 2000 mg/kg bodyweight. Deaths were noted two to three days after treatment. Major signs of toxicity noted during the day of dosing were hunched posture, pilo-erection, lethargy , decreased respiratory rate, increased salivation and ptosis. Less frequent signs of ataxia, pallor of the extremities, diarrhoea, diuresis, chromodacryorrhoea, tiptoe gait, emaciation, red/brown staining around the snout/eyes were also noted. Signs of reaction continued to be noted up to three to fourteen days after treatment. Surviving animals treated with 1000 mg/kg showed expected body weight gains over the study period. Effects on body weight were noted in other dose groups during the first week but all animals recovered to show expected body weight gains over the second week. Necropsy of decedents revealed congested or abnormally red lungs, dark livers , haemorrhage of the gastric mucosa with congestion of the small intestines. Necropsy of animals killed at the end of the study revealed thickened or raised white areas on the non-glandular region of the stomach. The acute oral median lethal dose (LDS0) and 95% confidence limits were found to be:

All animals: 1260 (1053 - 1508) mg/kg body weight

Males only: 1309 (1024 - 1674) mg/kg body weight

Females only: between 1000 and 1587 mg/kg body weight (best estimate).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 260 mg/kg bw

Quality of whole database:

Sufficient.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is no acute oral toxicity data for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs. also known as di-(2-hydroxypropyl) C16-C18 (evennumbered), C18 unsaturated-alkyl amine CAS No 1309955 -79 -0. There is a study available that have derived oral LD50 values for the read across source substance 2,2'-(Octadec-9-enylimino)bisethanol, CAS No. 25307-17-9.

 

The only study available is an oral LD50 study (According to OECD 401 and GLP compliant) on 2,2'-(Octadec-9-enylimino)bisethanol, CAS No. 25307-17-9, resulting to LD50 of 1260 (1053 - 1508) mg/kg body weight. Necropsy of the decedents showed haemorrhage of the gastric mucosa with congestion of the small intestines, and necropsy of animals killed at the end of the study revealed thickened or raised white areas on the non-glandular region of the stomach. This is indicative that the acute toxicity is mainly caused via local, corrosive, effects on the Gastro-intestinal system.

 

di-(2-hydroxypropyl) C16-C18 (evennumbered), C18 unsaturated-alkyl amine is considered corrosive to the skin. Testing for acute dermal toxicity is therefore not justified. Toxicity following dermal exposure is characterised by local tissue damage, rather than the result of percutaneously absorbed material. For corrosive substances, the use of protective gloves and other equipment, such as face shields, aprons and good work practices are mandatory. Consequently, the occurrence of substantial dermal exposure of amounts comparable to the levels for acute oral toxicity is unlikely.

 

di-(2-hydroxypropyl) C16-C18 (evennumbered), C18 unsaturated-alkyl amine is a liquid with a low vapour pressure, and exposure to vapours would be negligible at ambient temperatures. Possible inhalation would have to involve aerosol (of large) droplets that will deposit mainly on upper airways. Due to the corrosive properties of the substance, local respiratory irritation can be expected to represent the first, and most prominent, effects following inhalation of aerosols.

 

Justification for selection of acute toxicity – oral endpoint

Most relevant read across study.

Justification for classification or non-classification

There is no acute oral toxicty data for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs but there is data for the read across substance, 2,2'-(Octadec-9-enylimino)bisethanol, CAS No. 25307-17-9. There was clear lethality in a validity 1 study this will be used as the basis for the classification etc. The 2,2'-(Octadec-9-enylimino)bisethanol was therefore classified in Category IV according to OECD-GHS. Based on this read across Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs will be classified as Category IV according to OECD-GHS.

 

There is no dermal LD 50 value for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs. also there is no data for the read across substnace 2,2'-(Octadec-9-enylimino)bisethanol, CAS No. 25307-17-9 but due to the corrosive nature of the substance it is not ethical to carry out this animal study. The corrosive classification of the Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs. Based on 2,2'-(Octadec-9-enylimino)bisethanol, CAS No. 25307-17-9 and the required risk management methods with minimise the potential for skin contact, so the lack of a dermal LD50 will not affect the safe handling of the substance.

 

We also have no inhalation LC50 data for Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs. or for the read across source substance 2,2'-(Octadec-9-enylimino)bisethanol, CAS No. 25307-17-9. However the target substance is a liquid with a low vapour pressure, significant exposure to vapours would not be expected at ambient temperatures so the lack of an inhalation LD50 is not considered significant as inhalation is not an expected route of exposure.

 

Due to the physical form of the Propanol, iminobis-, N-C16-C18 (evennumbered), C18 unsatd. alkyl) derivs. being a solid/paste at ambient temperature, the is no aspiration hazard for this substance.