3-cyclohexylaminopropylamine

Endpoint summary

Description of key information

The test substance is harmful if swallowed with an oral LD50 (rat) between 200 - 237 mg/kg bw/d (Abbott Labs, 1963).

After single inhalation whole body exposure of young CD rats to the test compound for 60 minutes, no toxicological effects could be seen during the 14 days observation period after the exposure.

Further, the compound is considered to be a severe skin irritant and possesses the ability to penetrate the skin and produce systemic toxicity and even death in the rabbit. For acute dermal toxicity the LD50 was determined to be between 632 and 2000 mg/kg bw/d.

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

Study period:

March 1963

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no statistics provided

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

weight range of rats was 170 to 260 grams

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Rats were fasted overnight, then given single oral dose of compound by stomach tube. The compound was given undiluted or as a 1:10 dilution in water.
After dosing, each rat was returned to its cage and provided with water and food.

Doses:

100, 215, 464, 1000, 2150 mg/kg

No. of animals per sex per dose:

5 per sex and dose

Control animals:

no

Details on study design:

After dosing, each rat was returned to its cage and provided with water and food. Close observations for signs of toxicity was maintained on each animal the next one or two hours, and at intervals the rest of the working day. Daily checks were made thereafter for seven days at which the general condition of the rats was evaluated and any deaths recorded.
Survivors at seven days were sacrifieced and gross autopsies performed on representatives remaining from the higher doses. Some animals dying during the first day were also autopsied.

Statistics:

not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 200 - <= 237 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 142 - <= 395 mg/kg bw

Based on:

test mat.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

>= 137 - <= 291 mg/kg bw

Based on:

test mat.

Mortality:

Mortality increased in lower dose groups from day 2 to 7 and in higher dose groups (from 464 mg/kg) from 1h to 2 days (see table)

Clinical signs:

other: Excessive salivation, depression, tremors, lacrimation, labored breathing, bloody urine, convulsions

Gross pathology:

At lethal doses extensive gastrointestinal hemorrhaging, urinary bladder hemorrhage.
At non lethal doses: Irritation to gastrointestinal tract, enlarged spleen, discolored kidneys and liver

		Mortality by days
Dose in mg/kg	sex	1 hour	1 day	2 days	3 days	4 days	5 days	6 days	7 days
2150	m	5/5
	f	5/5
1000	m	5/5
	f	5/5
464	m	4/5	4/5	5/5
	f	5/5
215	m						1/5		1/5
	f			2/5					2/5
100	m			1/5					1/5
	f								0/5

Conclusions:

Based on the test results of the acute oral toxicity study in rats, the LD50 is estimated to be between 200 - 237 mg/kg.

Executive summary:

The acute oral toxicity of the test compound was determined in groups of albino rats consisting of five males and five females. The test material was administrated by gavage once and the animals were observed for seven days. The tested dose concentrations were 100, 215, 464, 100 and 2150 mg/kg. Based on the test results of the acute oral toxicity study in rats, the LD50 is estimated to be between 200 - 237 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Quality of whole database:

Klimisch 2

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978-09-13 to 1978-09-27

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Exposure duration 60 minutes, higher limit dose

GLP compliance:

no

Test type:

traditional method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CD rats derived by Charles River

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals purchased from Charles River Breeding Laboratories. Rats were individually housed in metal hanging cages of appropriate size prior to exposure and in plastic crispers with Sanicel bedding during the observation period. All animals were maintained in isolated temperature and humidity controlled animal rooms with filtered air supply and cycled lighting (12 hours of light daily). Purina Laboratory Chow and tested tap water were available ad libitum, except during the exposure time. Rats were acclimated for at least one week prior to initiation of the study.
Rats were selected from stock animals on the basis of body weight and general good health and allocated 5 males and 5 females per dose group. Body weight of young adult rats was between 194 - 238 g.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

>= 0.5 - <= 3 µm

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

The test material was metered from a 3 L reservoir into the continous feed nebulizer chamber of a Devilbiss Ultrasonic Nebulizer (Model 6582)capable of delivering liquid particles in a size range of 0.5 to 3.0 microns. A steam of filtered air wa passed through the nebulizer to produce concentrated aerosol which was introduced into the chamber at the top. The average nominal exposure concentration was calculated by dividing the total weight loss of the test material by the total volume of air used for aerosolination and dilution over the period of operation. The test atmosphere was exhausted at the bottom through an activated charcoal filter to archieved dynamic flow through the chamber.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

ca. 60 min

Remarks on duration:

After single exposure for 60 minutes the rats were observed for the following 14 days

Concentrations:

7.5 mg/L

No. of animals per sex per dose:

5 groups of 5 males and 5 females (50 animals)

Control animals:

yes

Remarks:

exposed to air only

Details on study design:

Each dose group was placed in a 400 L stainles steal and glass inhalation chamber and caged individually in stainless steal wire mesh cages ( 5 x 5 x 18 cm).

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 7.5 mg/L air

Exp. duration:

60 min

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

no effects during the 14 day observation period

Clinical signs:

other: no signs of toxicity observed

Body weight:

no differences between control and dosed groups and no differences between males and females

Gross pathology:

Gross necropsy of all rats after 14 days and examination of the major organs did not reveal any remarkable changes that were attributed to treatment.

Conclusions:

Under the conditions of this test, the LC50 could not be determined for the test compound. Based on the results, the LC50 would be greater than 7.5 mg/L.

Executive summary:

After single whole body exposure of young CD rats to the test compound for 60 minutes, no toxicological effects could be seen during the 14 days observation period after the exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Quality of whole database:

Klimisch 2

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:

March 1963

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

study review

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

sex not specified, test substance not removed after 24 h, no statistics, only 3 animals per dose group used, shorter observation period of 7 days

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

other: Albino

Sex:

not specified

Details on test animals or test system and environmental conditions:

Rabbits weighting between 2.0 and 2.8 kg

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

Three dose groups were used in the study. All rabbits were prepared for the test by closely clipping the fur over the trunk and each rabbit was given a single application of the test compound. The test material was spread evenly over the back by a glass rod, and the rabbit was then wrapped in gauze and covered by a further wrapping of rubber damming, fastened with adhesive tape. The rabbits were then returned to their cages where food and water were available.

Duration of exposure:

After single exposure of test material, the animals were observed for seven days.

Doses:

Group 1 2000 mg/kg 3 rabbits
Group 2 632 mg/kg 3 rabbits
Group 3 200 mg/kg 3 rabbits

No. of animals per sex per dose:

3 animals per dose

Control animals:

no

Details on study design:

Three dose groups. All rabbits were prepared for the test by closely clipping the fur over the trunk and each rabbit was given a single application of the test compound. The test material was spread evenly over the back by a glass rod, and the rabbit was then wrapped in gauze and covered by a further wrappingof rubber damming, fastened with adhesive tape.. The rabbits were then returned to their cages where food and water were available.

Key result

Sex:

not specified

Dose descriptor:

LD100

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 632 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All rabbits in the high dose group died within 28 hours after dosing

Clinical signs:

other: Considerably pain in the HD and MD dose group because the animals in these dose groups screamed for several minutes after application if test compound

Gross pathology:

Badly damaged skin and necrosis in the MD animals. In dead animals of the HD group: Black thickened skin and internally adhesions of cecum and portions of small intestine to the peritoneal lining of one rabbit receiving 632 mg/kg.

Acute Dermal toxicity for the Rabbit

Rabbit No	Dose in mg/kg	Body weight initial [kg]	Body weight sacrifice [kg]	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7	Autopsy
1	2000	2.3		dead							Compound has burned through all layers of skin and the entire intestinal tract appeared hemorrhagic
2	2000	2.0		XXX							Pupils dilatated, weak, depressed apperance
Erythema					dead
Edema
3	2000	1.9		dead							Compound has burned through skin
4	632	2.0	1.7								Pupils dilated
Erythema				XXX	XXX	XXX	XXX	Black, necrotic		sac
Edema				XXX	XXX	XXX	XXX
5	632	2.1	1.8								Pupils dilated
Erythema				XXX	XXX	XXX	XXX	Black, necrotic		sac
Edema				XXX	XXX	XXX	XXX
6	632	2.3	1.9								Pupils dilated
Erythema				XXX	XXX	XXX	XXX	necrotic		sac
Edema				XXX	XXX	XXX	XXX
7	200	2.4	2.2								Pupils slightly dilated
Erythema				XXX	XXX	XX	XX	necrotic		sac
Edema				XXX	XXX	XXX	XXX
8	200	2.3	2.1								Pupils slightly dilated
Erythema				XXX	XXX	XX	XX	necrotic		sac
Edema				XXX	XXX	XXX	XX
9	200	2.4	2.2								Pupils slightly dilated
Erythema				XXX	XXX	XX	XX	necrotic		sac
Edema				XXX	XXX	XXX	XX

Conclusions:

The compound is considered to be a severe skin irritant and possesses the ability to penetrate the skin and produce systemic toxicity and even death in the rabbit.

Executive summary:

Nine albino rabbits were divided into three dose groups of 200, 632 and 2000 mg/kg. The test material was applied to the clipped skin once and then the rabbit was wrapped in gauze and covered by wrapping of rubber damming. All three rabbits of the high dose died within the first 28 h after dosing. All survivors lost 300 - 400 g in body weight. The skin wad badly damaged in all cases and showed severe necrosis. Post-mortem observations on survivors included: black, thickened skin and internally adhesions of cecum and portions of small intestine to the peritoneal lining of one rabbit in MD.

The compound must be considered as severe skin corrosive and possesses the ability to penetrate the skin and to produce systemic toxicity and the LD 50 value was determined to be between 632 and 2000 mg/kg bw/d.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Quality of whole database:

Klimisch 2

Justification for classification or non-classification

Based on the results of the acute oral study in rats and according to criteria of CLP regulation 1272/2008, the test item is classified in the hazard category 3, required labelling with 'Danger' and 'Toxic if swallowed'. The acute inhalation study showed no toxicity and the substance does not need to be classified. In the dermal acute study, the compound revealed adverse systemic effects and according to GHS has to be classified in the hazard category 3 required labelling with 'Danger' and 'Toxic in contact with skin'.